ABSTRACT While the function of biglycan (BGN) is recognized in various cancers, its precise role and the mechanisms underlying cancer‐associated fibroblasts (CAFs) formation within the melanoma tumor microenvironment (TME) remain poorly understood. Utilizing spatial transcriptomics, single‐cell RNA sequencing (scRNA‐seq), vitro/vivo assays, function analysis and molecular assays, this study comprehensively investigated the BGN regulatory network. We discovered that N6‐methyladenosine (m6A) modulators—specifically YTHDF3, YTHDC1, and METTL14—cooperatively upregulate BGN expression in a parallel, non‐hierarchical manner converging on functional m6A sites within melanoma cells. Consequently, BGN significantly promoted melanoma proliferation and metastasis. Within the TME, spatial transcriptomics and scRNA‐seq revealed that CAFs, rather than tumor cells, exhibited the highest BGN expression. Cell trajectory analysis indicated that myCAFsBGN‐high may originate from iCAFsBGN‐low to interact with melanoma cells. Furthermore, midkine (MDK) signaling pathways was identified by cell chat analysis. Transcriptomic and spatial analysis revealed that BGN could regulate its expression at RNA and protein levels in CAFs through the regulator AE binding protein 1 (AEBP1). And the tumor promotion effect of CAFs may be executed by BGN/MDK axis, which also reduced CD8⁺ T cell infiltration in TME. Pharmacological inhibition of MDK also suppressed tumor growth with increased CD8⁺ T cell infiltration. Finally, this BGN/MDK axis could also drive the activation of normal fibroblasts into a CAF‐like phenotype verified by vitro assays. In conclusion, the interplay between cancer cells and CAFs mediated by the BGN/MDK axis is a critical driver of malignancy in melanoma, highlighting it as a promising therapeutic target for intervention.

Malignant melanoma, a highly aggressive form of skin cancer, has its progression, metastasis, and treatment resistance closely linked to profound metabolic reprogramming. Emerging research highlights that the rewiring of glucose and amino acid metabolism plays a central role in oncology, offering promising new directions for the treatment of this malignancy. With a focus on malignant melanoma, this review discusses how glucose and amino acid metabolism become dysregulated and presents the mechanistic basis for this rewiring. Metabolic reprogramming is a key mechanism through which tumors condition their microenvironment to support expansion and avoid immune detection. By synthesizing current evidence, this article aims to pinpoint promising directions for future research and therapy in this challenging disease.

Liver metastasis is a major cause of mortality in gastric cancer (GC), yet the underlying molecular mechanisms remain poorly understood. Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression and cancer progression, but their roles in GC liver metastasis are not fully defined. In this study, lncRNA sequencing of primary GC tumors and matched liver metastatic tissues identified PSPC1-AS2 as significantly upregulated. Its elevated expression was further validated across multiple patient cohorts and public datasets. Functional assays demonstrated that PSPC1-AS2 promotes GC cell migration, invasion, and liver metastasis both in vitro and in vivo. Mechanistically, PSPC1-AS2 is predominantly localized in the nucleus and enhances the mRNA stability of its neighboring gene PSPC1 by recruiting the RNA-binding protein EIF4A3. The PSPC1-AS2/PSPC1 axis facilitates tumor progression and induces macrophage polarization toward the pro-tumorigenic M2 phenotype via increased CCL2 secretion. At the molecular level, PSPC1 interacts with PARP1, competitively inhibiting PARP1-mediated PARylation and dephosphorylation of STAT3, thereby sustaining STAT3 activation and promoting CCL2 transcription. Notably, neutralization of CCL2 effectively reverses PSPC1-induced M2 macrophage polarization. Collectively, these findings reveal a novel PSPC1-AS2/PSPC1/STAT3/CCL2 regulatory axis that drives GC progression and liver metastasis through remodeling of the tumor microenvironment, highlighting a potential therapeutic target for advanced gastric cancer.

Objective::N6-methyladenosine (m6A) modification and cuproptosis play essential roles in the pathogenesis of various malignant tumors. However, the predictive role of m6A regulators and cuproptosis-related genes in skin cutaneous melanoma (CM) remains unclear. In this study, the aim was not only to explore the role of m6A modification in CM, but also to investigate the differential expression of cuproptosis-related genes in different risk group.Methods::We obtained transcriptome data from the XENA and Genotype-Tissue Expression databases. Univariate Cox regression analysis was performed to investigate the relationship between m6A-related genes and the outcomes of CM. Least absolute shrinkage and selection operator regression analysis was utilized to construct a risk model. Moreover, we analyzed immune cell infiltration using CIBERSORT algorithms. Finally, we evaluated the expression levels of cuproptosis-related genes in CM samples and performed reverse-transcription quantitative polymerase chain reaction to validate the expression of cuproptosis-associated genes in melanoma cells after YTHDF3 knockdown. Student’s t-test was used to analysis the difference between two groups. Results::All m6A-related genes differed in melanoma tissues and normal tissues and a prognostic signature was developed. Immune infiltration revealed that low-risk group patients had a higher level of CD8 + T cells, memory activated CD4 + T cells, activated natural killer cells and M1 macrophages than high-risk group (all P < 0.05). Moreover, the cuproptosis-related genes MTF-1, PDHB, and FDX1 were significantly negatively associated with risk score ( P < 0.01, P < 0.01, and P = 0.04, respectively). We also found that downregulation YTHDF3 in melanoma cells affected the expression of cuproptosis-related genes MTF1, PDHB, LIAS, GLS, DLAT, DLD, and PDHA1 (all P < 0.05). Conclusion::Our study demonstrated the prognostic value of m6A-related genes and cuproptosis-related genes in CM, providing new potential predictive and therapeutic targets for CM.

Glucose metabolic reprogramming is a hallmark of cancer, best exemplified by the Warburg effect. It plays a central role in driving tumour growth, metastasis and resistance to therapy. This review systematically delineates the molecular underpinnings of this metabolic shift, encompassing the roles of key glycolytic enzymes, transporters, oncogenic signalling pathways and multilayered epigenetic regulation. We further propose a novel framework that conceptualizes glucose metabolism as an integrated system for signal transduction and niche engineering, which remodels the tumour microenvironment to promote immunosuppression. Finally, we highlight the translational applications of these insights, including metabolic imaging for diagnosis and prognosis and therapeutic strategies targeting glycolytic pathways, applied both as monotherapies and in rational combinations with conventional and emerging treatments. Targeting glucose metabolic reprogramming offers a promising perspective and novel strategies for cancer diagnosis and therapy.

Recent studies have identified N6-methyladenosine (m6A) RNA methylation as a key regulatory mechanism in tumor progression. This study aimed to elucidate the biological function and clinical relevance of the m6A methyltransferase METTL3 in cutaneous T-cell lymphoma (CTCL). Our findings demonstrated that METTL3 expression is upregulated in CTCL, and its knockdown suppresses CTCL progression. Mechanistically, the downregulation of METTL3-mediated m6A modification on ARHGEF12 mRNA accelerated its degradation, a process that is closely associated with tumor behaviors. These results suggest that METTL3 may serve as a potential therapeutic target in CTCL.

In the original publication [...].

Background:Cutaneous melanoma (SKCM) remains a lethal malignancy with complex molecular mechanisms. PANoptosis, a coordinated cell death pathway, and long noncoding RNAs (lncRNAs) have emerged as critical modulators influencing oncogenic pathways and tumor development through multifaceted regulatory mechanisms. This study aimed to identify PANoptosis regulator (PANR)-associated lncRNAs and construct a prognostic model to predict SKCM outcomes and to clarify their associations with immune infiltration, drug sensitivity, and molecular pathways. Methods:Gene expression data from 471 The Cancer Genome Atlas (TCGA)-human skin SKCM tumors, 214 Gene Expression Omnibus-SKCM samples, and 812 Genotype-Tissue Expression normal tissues were merged after batch correction. A PANR set (n=300) was integrated to identify differentially expressed PANRs (DE-PANRs) and identify differentially expressed lncRNAs (DE-lncRNAs) using the "limma" package [false discovery rate (FDR) <0.05 and |log2 fold change| >1]. Associations between DE-lncRNAs and DE-PANRs were established through Pearson correlation analysis and followed by functional enrichment via Database for Annotation, Visualization and Integrated Discovery (DAVID). Prognostic DE-lncRNAs were selected via univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. A risk score (RS) model was developed and validated in the TCGA and GSE65904 cohorts. Nomogram construction, immune profiling (CIBERSORT), drug sensitivity (pRRophetic), and pathway analyses [gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG)] were performed. Results:Differential analysis identified 995 DE-lncRNAs and 142 DE-PANRs, with 83 PANR-associated lncRNAs forming a regulatory network. Six prognostic lncRNAs (MIR155HG, LINC01501, NRIR, HLA-DQB1-AS1, USP30-AS1, and LINC00674) were optimized via LASSO. Survival disparities were observed between the high- and low-risk cohorts stratified by the RS model [TCGA cohort: hazard ratio (HR) =2.72, P<0.001; GSE65904 cohort: HR =1.85, P=0.002]. The nomogram integrating RS, age, and tumor stage could predict the 1-, 3-, and 5-year survival (concordance index =0.81). High-risk patients exhibited immunosuppressive profiles and showed differential drug response patterns, with predicted increased sensitivity to 14 therapeutic agents. Enriched pathways included apoptosis, inflammatory response, and KRAS signaling. Mutational analysis revealed the top 20 mutated genes that differed the most between risk groups. Conclusions:This study established a PANR-associated lncRNA prognostic model with robust predictive accuracy for SKCM survival. The risk stratification system correlates with immune dysregulation, therapy response, and pathway activation, offering a potential tool for personalized prognosis and treatment strategies.

BackgroundAs the most important modifications on the RNA level, N6-methyladenosine (m6A-) and 5-methylcytosine (m5C-) modification could have a direct influence on the RNAs. Long non-coding RNAs (lncRNAs) could also be modified by methylcytosine modification. Compared with mRNAs, the function of lncRNAs could be more potent to some extent in biological processes like tumorigenesis. Until now, rare reports have been done associated with cutaneous melanoma. Herein, we wonder if the m6A- and m5C- modified lncRNAs could influence the immune landscape and prognosis in melanoma, and we also want to find some lncRNAs which could directly affect the malignant behaviors of melanoma.MethodsSystematically, we explored the expression pattern of m6A- and m5C- modified lncRNAs in melanoma from datasets including UCSC Xena and NCBI GEO, and the prognostic lncRNAs were selected. Then, according to the expression pattern of lncRNAs, melanoma samples from these datasets were divided into several subtypes. Prognostic model, nomogram survival model, drug sensitivity, GO, and KEGG pathway analysis were performed. Furthermore, among several selected lncRNAs, we identified one lncRNA named LINC00893 and investigated its expression pattern and its biological function in melanoma cell lines.ResultsWe identified 27 m6A- and m5C- related lncRNAs which were significantly associated with survival, and we made a subtype analysis of melanoma samples based on these 27 lncRNAs. Among the two subtypes, we found differences of immune cells infiltration between these two subtypes. Then, LASSO algorithm was used to screen the optimized lncRNAs combination including ZNF252P-AS1, MIAT, FAM13A-AS1, LINC-PINT, LINC00893, AGAP2-AS1, OIP5-AS1, and SEMA6A-AS1. We also found that there was a significant correlation between the different risk groups predicted based on RS model and the actual prognosis. The nomogram survival model based on independent survival prognostic factors was also constructed. Besides, sensitivity to chemotherapeutic agents, GO and KEGG analysis were performed. In different risk groups, a total of 14 drug molecules with different distributions were obtained, which included AZD6482, AZD7762, AZD8055, camptothecin, dasatinib, erlotinib, gefitinib, gemcitabine, GSK269962A, nilotinib, rapamycin, and sorafenib. A total of 55 significantly related biological processes and 17 KEGG signaling pathways were screened. At last, we noticed that LINC00893 had a relatively lower expression in melanoma tissue and cell lines compared with adjacent tissues and epidermal melanocyte, and down-regulation of LINC00893 could promote the malignant behavior of melanoma cells in A875 and MV3. In these two melanoma cell lines, down-regulation of m6A-related molecules like YTHDF3 and METTL3 could promote the expression of LINC00893.ConclusionWe made an analysis of m6A- and m5C- related lncRNAs in melanoma samples and a prediction of these lncRNAs' role in prognosis, tumor microenvironment, immune infiltration, and clinicopathological features. We also found that LINC00893, which is potentially regulated by m6A modification, could serve as a tumor-suppressor in melanoma and play an inhibitory role in melanoma metastasis.

Experimental DermatologyVolume 33, Issue 1 e14992 RESEARCH LETTER Single-cell RNA sequencing reveals the underlying mechanism of folliculotropism in folliculotropic mycosis fungoides Hao-ze Shi, Hao-ze Shi orcid.org/0000-0002-6718-9675 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorCui-cui Tian, Cui-cui Tian Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYing-qi Kong, Ying-qi Kong Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorJian-fang Sun, Corresponding Author Jian-fang Sun [email protected] Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence Jian-fang Sun and Hao Chen, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China. Email: [email protected] and [email protected]Search for more papers by this authorHao Chen, Corresponding Author Hao Chen [email protected] Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence Jian-fang Sun and Hao Chen, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China. Email: [email protected] and [email protected]Search for more papers by this author Hao-ze Shi, Hao-ze Shi orcid.org/0000-0002-6718-9675 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorCui-cui Tian, Cui-cui Tian Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYing-qi Kong, Ying-qi Kong Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorJian-fang Sun, Corresponding Author Jian-fang Sun [email protected] Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence Jian-fang Sun and Hao Chen, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China. Email: [email protected] and [email protected]Search for more papers by this authorHao Chen, Corresponding Author Hao Chen [email protected] Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence Jian-fang Sun and Hao Chen, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China. Email: [email protected] and [email protected]Search for more papers by this author First published: 21 December 2023 https://doi.org/10.1111/exd.14992 Hao-ze Shi, Cui-cui Tian, and Ying-qi Kong are contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Open Research DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. REFERENCES 1Gaydosik AM, Stonesifer CJ, Tabib T, Lafyatis R, Geskin LJ, Fuschiotti P. The mycosis fungoides cutaneous microenvironment shapes dysfunctional cell trafficking, anti-tumor immunity, matrix interactions and angiogenesis. JCI Insight. 2023; 8:e170015. 10.1172/jci.insight.170015 PubMedWeb of Science®Google Scholar 2Sigmundsdottir H, Pan J, Debes GF, et al. DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007; 8: 285-293. 10.1038/ni1433 CASPubMedWeb of Science®Google Scholar 3Collins CA, Watt FM. Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for beta-catenin and Notch signalling. Dev Biol. 2008; 324: 55-67. 10.1016/j.ydbio.2008.08.034 CASPubMedWeb of Science®Google Scholar 4Tabib T, Morse C, Wang T, Chen W, Lafyatis R. SFRP2/DPP4 and FMO1/LSP1 define major fibroblast populations in human skin. J Invest Dermatol. 2018; 138: 802-810. 10.1016/j.jid.2017.09.045 CASPubMedWeb of Science®Google Scholar 5Badshah II, Brown S, Weibel L, et al. Differential expression of secreted factors SOSTDC1 and ADAMTS8 cause profibrotic changes in linear morphoea fibroblasts. Br J Dermatol. 2019; 180: 1135-1149. 10.1111/bjd.17352 CASPubMedWeb of Science®Google Scholar Volume33, Issue1January 2024e14992 ReferencesRelatedInformation

Evidence has shown that endoplasmic reticulum (ER) stress plays a role in the regulation of skin physiological functions such as melanocyte transformation and keratinocyte-related epidermal homeostasis. Other pathological processes may also be influenced. Recently, more evidence has suggested that ER stress participates in the pathogenesis of melanoma. Many biological functions of melanoma can be affected by the disturbance of ER stress. We herein review the network of ER stress and its role in melanoma and discuss several chemicals or drugs that may act as tumor inhibitors by influencing ER stress.

Background:Hypopigmented mycosis fungoides (hMF) is gradually acknowledged by more dermatologists, yet a consensus regarding its characteristics is not reached. The profile of Chinese hMF patients has not been deeply reviewed previously. Our research may contribute to the understanding of hMF, especially the Chinese patients with Fitzpatrick phototypes of III and IV.Aim:To have a better understanding of hMF in terms of clinical, histopathological and immunohistochemical features in the Chinese population and to determine if there are differences between the Chinese population and other ethnic groups.Methods:We made a retrospective analysis of clinical, histopathological and immunohistochemical features of 32 hMF patients in our hospital from 2010 to 2020. These features were then summarized and compared with previous reports.Results:All patients belonged to Fitzpatrick phototypes of III or IV. Twenty-one male (65.63%) patients and 11 female (34.37%) patients were analyzed, and the male to female ratio was 1.9:1. The age at diagnosis of patients ranged from 4 to 39 years, and the average age at diagnosis of these patients was 18 years, the median age was 16.5. Back was the most frequent site (34.37%). The clinical and histological results of lesions had no distinctive points. Immunohistochemically, among these 32 patients, there were 30 patients whose information was complete, there was 19 patients (63.33%) who were CD8 positive lymphocytes predominance, 9 patients (30%) had CD8 and CD4 positive lymphocyte mixed infiltration, and other 2 patients (6.67%) had CD4 positive lymphocytes predominance. Partial loss of CD7 was only observed in 1 patient (3.33%). Nearly all patients adopted topical nitrogen mustard and topical steroid and most of them had an excellent prognosis.Conclusion:The clinical profiles of hMF in Chinese population shared differences with other ethnic groups, but its histopathological, immunohistochemical results and prognosis condition were resembled with other previous reports. Hence, more patients were needed to find the characteristics of hMF.

Background A number of studies have demonstrated that N6‐methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive. Methods RT‐qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6–methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase–like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi‐omics analysis including RNA‐seq, MeRIP‐seq, RIP‐seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT‐PCR, Western blot, MeRIP‐qPCR, RIP‐qPCR and CRISPR‐Cas13b‐based epitranscriptome engineering. Results In this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA‐binding protein 7 (CHD7) were identified by means of RNA‐seq, MeRIP‐seq, RIP‐seq and mass spectrometry analyses. Besides, RT‐qPCR, Western blot, RIP‐qPCR and MeRIP‐qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR–Cas13b‐based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation. Conclusions The YTHDF3‐LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma; in advanced stages, it can involve multiple organs and has a poor prognosis. Early detection of the disease is still urgent, but there is no optimal therapy for advanced MF. In the present study, quantitative proteomic analyses (label-free quantitation, LFQ) were applied to tissue samples of different stages of MF and tissue samples from controls (eczema patients and healthy donors) to conduct preliminary molecular analysis to clarify the pathogenesis of the disease. Differential protein expression analysis demonstrated that 113 and 305 proteins were associated with the early and advanced stages of MF, respectively. Gene ontology (GO) enrichment analysis was conducted to determine the potential functions of the proteins, which could be classified into three categories: biological process, cellular component, and molecular function. The results revealed that a series of biological processes, including “initiation of DNA replication” and “nucleosome assembly,” were involved in the disease. Moreover, cellular components, including the “desmosome” and “integrin complex,” may affect the invasion and metastasis of MF via molecular functions, including “integrin binding” and “cadherin binding”. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that “focal adhesion DNA replication,” “Toll-like receptor signalling pathway” and other pathways were also involved. A parallel reaction monitoring (PRM) assay was applied to validate the identified differentially expressed proteins. In conclusion, the above proteomic findings may have great diagnostic and prognostic value in diverse malignancies, especially MF. Nevertheless, further studies are still needed to explore the precise mechanisms of MF.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Objective:To investigate the expression of epigenetic inhibitor polycomb group proteins such as enhancer of zeste homolog 1/2 (EZH1/EZH2), embryonic ectoderm development protein (EED) and suppressor of zeste 12 (SUZ12) in common cutaneous T-cell lymphomas and lymphoproliferative disorders (CTCL/LPD) .Methods:Totally, 93 paraffin-embedded skin samples of CTCL/LPD and 8 of lichen planus were collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College between 2012 and 2019, and subjected to immunohistochemical staining to determine the protein expression of EZH2, EED, SUZ12 and EZH1. Statistical analysis was carried out with SPSS 25.0 software by using chi-square test and Spearman correlation analysis.Results:The 93 cases of CTCL/LPD included 44 cases of mycosis fungoides (MF), 17 natural killer/T cell lymphoma (NK/TCL), 8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL), 8 lymphomatoid papulosis (LyP), 8 hydroa vacciniforme-like lymphoproliferative disorder (HV-like LPD) and 8 cases of subcutaneous panniculitis-like T cell lymphoma (SPTCL). Among the 93 CTCL/LPD cases, 83 (89.2%) were positive for EZH2, 81 (87.1%) for EED, 78 (83.9%) for SUZ12 and 37 (39.8%) for EZH1; among the 8 cases of lichen planus, 1 was positive for EZH2, all were positive for EZH1, and all were negative for EED and SUZ12. The expression of EZH2, EED, SUZ12 and EZH1 in lichen planus samples significantly differed from all the CTCL/LPD samples ( χ2 = 41.75, 39.74, 39.36, 32.83, respectively, all P < 0.001), and from MF, NK/TCL, PC-ALCL, LyP, HV-like LPD and SPTCL samples separately (α = 0.008 3, all P < 0.001). Meanwhile, the score of EZH2 expression was negatively correlated with that of EZH1 expression in the MF, NK/TCL, PC-ALCL, LyP, HV-like LPD and SPTCL tissues ( rs = -0.60, -0.68, -0.89, -0.74, -0.93, -0.80, respectively, all P < 0.05) . Conclusion:Polycomb group proteins EZH2, EED, SUZ12 and EZH1 are abnormally expressed in CTCL/LPD lesions.

BACKGROUND:Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder has been defined as a type of lymphoproliferative disorder with indolent clinical course and excellent prognosis, yet a precise diagnosis is still hard to reach.METHODS:A retrospective analysis of 22 patients including 16 females and six males was performed.RESULTS:The age of patients ranged from 5 to 79 years. The average age of all patients was 43.5, and the median age of all patients was 44.5. Two patients had multiple lesions, and others were presented with a solitary asymptomatic lesion. Besides general features, folliculotropism was observed in four cases. In addition to express CD3 and CD4, CD30 were positive to some extent. Some reactive cells could express CD8 and CD20. For follicular helper T-cell markers, although CXCL-13 was negative in the stained cases (18/18), the expression of PD-1 (12/17), BCL-6 (12/16) and CD10 (11/15) was observed in most cases. In addition, we performed T-cell receptor (TCR) rearrangement on five patients, and all of them showed monoclonality. Nearly all patients had excellent prognosis.CONCLUSIONS:Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder is complex. Some features like folliculotropism should also be noted. Besides, the expression of follicular helper T-cell markers is not invariable. Moreover, CD8 positivity, Ki-67 index, and lesion number were perhaps not absolute prognostic indicators. To reach a diagnosis of this rare entity, putting all the pieces together is important.

Melanoma is a rare but fatal form of skin cancer and acral lentiginous melanoma (ALM) is one of its most common types. Long non-coding RNA (lncRNA) has emerged as a crucial molecule in the development and progression of human cancers, and several studies have revealed that lncRNAs may be associated with the pathogenesis, progression and metastasis of melanoma. To demonstrate the association between ALM and lncRNAs, microarray analysis was performed in tumor and adjacent non-tumor tissues. A total of 4,488 lncRNAs and 3,913 mRNAs were identified to be differentially expressed in these samples. Among them, 2,211 and 2,277 lncRNAs were upregulated and downregulated in the ALM samples compared with adjacent tissues, respectively. In addition, 1,191 and 2,722 mRNAs were upregulated and downregulated, respectively. Additionally, five randomly selected lncRNAs (fold-change >2; P<0.05) were validated by reverse transcription-quantitative PCR. An lncRNA and mRNA co-expression network and competing endogenous network analysis were also constructed. In summary, the results of the present study may reveal a novel mechanism associated with the pathogenesis and malignant biological processes of ALM and indicate that lncRNAs may serve as potential targets for the treatment of ALM.

British Journal of DermatologyVolume 181, Issue 6 p. 1332-1333 Research Letter Clinical characteristics of primary cutaneous lymphoma: analysis from two centres in China H.-Z. Shi, H.-Z. Shi orcid.org/0000-0002-6718-9675 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorY.-X. Liu, Y.-X. Liu Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, ChinaSearch for more papers by this authorY.-Q. Jiang, Y.-Q. Jiang Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorS.-L. Chen, S.-L. Chen Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, ChinaSearch for more papers by this authorX.-L. Xu, X.-L. Xu Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorX.-M. Lu, X.-M. Lu Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, ChinaSearch for more papers by this authorW. Zhang, W. Zhang orcid.org/0000-0001-9968-0023 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorX.-S. Zeng, X.-S. Zeng Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorG.-Z. Zhou, Corresponding Author G.-Z. Zhou zhou_guizhi2003@163.com Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, China Correspondence: Hao Chen; Jian-fang Sun and Gui-zhi Zhou. E-mails: ch76ch@163.com; fangmin5758@aliyun.com; zhou_guizhi2003@163.comSearch for more papers by this authorJ.-F. Sun, Corresponding Author J.-F. Sun fangmin5758@aliyun.com Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence: Hao Chen; Jian-fang Sun and Gui-zhi Zhou. E-mails: ch76ch@163.com; fangmin5758@aliyun.com; zhou_guizhi2003@163.comSearch for more papers by this authorH. Chen, Corresponding Author H. Chen ch76ch@163.com orcid.org/0000-0003-0857-7405 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence: Hao Chen; Jian-fang Sun and Gui-zhi Zhou. E-mails: ch76ch@163.com; fangmin5758@aliyun.com; zhou_guizhi2003@163.comSearch for more papers by this author H.-Z. Shi, H.-Z. Shi orcid.org/0000-0002-6718-9675 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorY.-X. Liu, Y.-X. Liu Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, ChinaSearch for more papers by this authorY.-Q. Jiang, Y.-Q. Jiang Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorS.-L. Chen, S.-L. Chen Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, ChinaSearch for more papers by this authorX.-L. Xu, X.-L. Xu Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorX.-M. Lu, X.-M. Lu Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, ChinaSearch for more papers by this authorW. Zhang, W. Zhang orcid.org/0000-0001-9968-0023 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorX.-S. Zeng, X.-S. Zeng Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorG.-Z. Zhou, Corresponding Author G.-Z. Zhou zhou_guizhi2003@163.com Department of Pathology, Shandong Provincial Institute of Dermatology and Venereology, Jinan, China Correspondence: Hao Chen; Jian-fang Sun and Gui-zhi Zhou. E-mails: ch76ch@163.com; fangmin5758@aliyun.com; zhou_guizhi2003@163.comSearch for more papers by this authorJ.-F. Sun, Corresponding Author J.-F. Sun fangmin5758@aliyun.com Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence: Hao Chen; Jian-fang Sun and Gui-zhi Zhou. E-mails: ch76ch@163.com; fangmin5758@aliyun.com; zhou_guizhi2003@163.comSearch for more papers by this authorH. Chen, Corresponding Author H. Chen ch76ch@163.com orcid.org/0000-0003-0857-7405 Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence: Hao Chen; Jian-fang Sun and Gui-zhi Zhou. E-mails: ch76ch@163.com; fangmin5758@aliyun.com; zhou_guizhi2003@163.comSearch for more papers by this author First published: 01 July 2019 https://doi.org/10.1111/bjd.18266Citations: 2 Funding sources: CAMS Innovation Fund for Medical Sciences (CIFMS-2017-12M-1-017); PUMC Youth Fund (No. 3332017168) and Six Major Talent Summit in Jiangsu Province (No. WSN-030). Conflicts of interest: none to declare. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume181, Issue6December 2019Pages 1332-1333 RelatedInformation