Disulfidptosis—a newly characterised mode of regulated cell death implicated in tumorigenesis—exhibits undefined prognostic utility in hepatocellular carcinoma (HCC), particularly concerning disulfidptosis-related long non-coding RNAs (DRLs). Integrating transcriptomic and clinical data from The Cancer Genome Atlas, we identified 807 DRLs and constructed a prognostic signature via univariate Cox regression, LASSO-Cox penalisation, and multivariate Cox analysis. The resulting four-DRL signature (AL031985.3, TMCC1-AS1, AL590705.3, AC026412.3) stratified patients into distinct risk cohorts, with high-risk groups demonstrating significantly reduced overall survival (OS; log-rank P < 0.001) and hazard ratios independent of conventional clinicopathological variables. Model discrimination was robust across multiple metrics: time-dependent receiver operating characteristic curves yielded AUCs of 0.750 (95

N-Myc downstream-regulated gene 3 (NDRG3), a member of the NDRG family, plays an important role in the development, progression, invasiveness, and metastasis of multiple tumor types. This study focuses on NDRG3 expression in epithelial ovarian cancer (EOC) and the correlation between NDRG3 expression and prognostic indicators. First, the LinkedOmics database was used to analyze the expression of genes associated with NDRG3, and then gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analyses and methylation analysis of NDRG3-related genes were performed to identify co-expressed genes. A protein–protein interaction network was constructed using the STRING database. Subsequently, quantitative polymerase chain reaction was performed to determine the mRNA expression level of NDRG3 in 22 fresh EOC tissue samples. In addition, immunohistochemistry was performed to detect the expression of NDRG3 protein in 110 EOC microarray samples. Cox regression and Kaplan–Meier survival analyses were performed to assess the prognostic value of NDRG3. Bioinformatics analysis showed that NDRG3 had a broad impact on the transcriptome and that genes that were co-expressed with NDRG3 were primarily involved in organ- or tissue-specific immune response, response to chemokine, interleukin-1 production, and other related pathways. The KEGG pathway analysis suggested that genes co-expressed with NDRG3 were also enriched in signaling pathways, including the interleukin-17 signaling pathway. The mRNA expression levels of NDRG3 were significantly higher in EOC tissues than in paracancerous nontumor tissues ( P < .01). NDRG3 expression in EOC was correlated with distant metastasis ( P = .02), tumor–node–metastasis stage ( P = .03), and patient prognosis ( P = .01). Moreover, the disease-free survival and overall survival times of EOC patients decreased with increasing NDRG3 expression. High NDRG3 expression and lymph node metastasis were identified as independent prognostic factors in 110 EOC patients. NDRG3 plays a key role in ovarian cancer progression. High NDRG3 expression is correlated with multiple clinicopathologic features of EOC and may be an indicator of a poor prognosis in EOC.

Background:Hepatocellular carcinoma (HCC) triggered by Hepatitis B virus (HBV) remains a significant clinical challenge, necessitating novel therapeutic interventions. Copper ionophores, recognized for introducing an innovative type of programmed cell death termed cuproptosis, present promising potentials for cancer therapy. Nevertheless, The role of cuproptosis-related lncRNAs (CRLRs) in HBV-HCC has not been clearly elucidated. Methods:This study utilised univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression analyses to establish a signature for CRLRs in HBV-HCC. This prognostic model was validated with an independent internal validation cohort, combined with clinical parameters, and used to construct a nomogram for patient survival predictions. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were employed to explore associated biological pathways. Additionally, a protein-protein interaction (PPI) network was developed, and implications for tumour mutational burden (TMB) and drug response were examined. A comprehensive bioinformatics analysis of these hub CRLRs was performed, followed by experimental validation through quantitative real-time PCR (qRT-PCR) and functional cellular assays. Results:The nomogram showed high predictive accuracy for HBV-HCC patient survival. GO and GSEA analyses indicated that these lncRNAs are involved in pathways related to cancer and oestrogen metabolism. A PPI network consisting of 201 nodes and 568 edges was developed, and the TMB and drug response differed significantly between high- and low-risk groups. Analyses identified three hub CRLRs, SOS1-IT1, AC104695.3, and LINC01269, which were significantly differentially expressed in HCC tissues. In vitro, LINC01269 was found to enhance HCC cell proliferation, invasion, and migration. Conclusion:The first systematic exploration of the roles of CRLRs in HBV-HCC demonstrates their critical involvement in the disease's pathogenesis and possible therapeutic implication. The distinct expression patterns and significant biological pathways suggest that these lncRNAs may facilitate novel therapeutic targets.

Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into an aggressive subtype, typically diffuse large B-cell lymphoma (DLBCL). The prognosis of transformed lymphoma is poor. In this study, we reported the efficacy and toxicity of a combination of venetoclax, dose-adjusted rituximab or obinutuzumab, etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide (VR-DA-EPOCH or VG-DA-EPOCH) in 11 patients with biopsy-proven histology transformation into DLBCL, including 8 patients with RT and 3 with transformed FL (tFL). The study was conducted between October 2019 and March 2023 at our single center. The median age of participants at enrolment was 53 years. Six patients (85.7%, 6/7) achieved complete remission (CR) at the end of treatment. The best overall response rate (ORR) and CR rate were both 72.7%, respectively. Two patients received autologous hemopoietic stem cell transplant (ASCT) while two patients received ASCT concurrently with CAR-T therapy for consolidation. With a median follow-up of 13.5 (range, 2.4–29.8) months after enrollment, the median event-free survival, progression-free survival, and overall survival were 9.4, 11.5, and 17.5 months, respectively. Hematologic toxicities of grade ≥3 consisted of neutropenia (90.9%, 10/11), thrombocytopenia (63.6%, 7/11), and febrile neutropenia (54.5%, 6/11). In conclusion, VR-DA-EPOCH or VG-DA-EPOCH was a promising strategy to achieve an early remission, bridging to cellular therapy within this population.

The progression of chronic kidney disease (CKD) often involves renal interstitial fibrosis (RIF) and subsequent loss of peritubular capillaries (PTCs), which enhances disease severity. Despite advancements in our understanding of fibrosis, effective interventions for reversing capillary loss remain elusive. Notably, RIF exhibits reduced capillary density, whereas renal cell carcinoma (RCC) shows robust angiogenesis under hypoxic conditions. Using RNA sequencing and bioinformatics, we identified differentially expressed genes (DEGs) in hypoxic human renal tubular epithelial cells (HK-2) and renal cancer cells (786-0). Analysis of altered Ras and PI3K/Akt pathways coupled with hub gene investigation revealed RAS protein activator-like 2 (RASAL2) as a key candidate. Subsequent in vitro and in vivo studies confirmed RASAL2's early-stage response in RIF, which reduced with fibrosis progression. RASAL2 suppression in HK-2 cells enhanced angiogenesis, as evidenced by increased proliferation, migration, and branching of human umbilical vein endothelial cells (HUVECs) co-cultured with HK-2 cells. In mice, RASAL2 knockdown improved Vascular endothelial growth factor A (VEGFA) and Proliferating cell nuclear antigen (PCNA) levels in unilateral ureteral occlusion (UUO)-induced fibrosis (compared to wild type). Hypoxia-inducible factor 1 alpha (HIF-1α) emerged as a pivotal mediator, substantiated by chromatin immunoprecipitation (ChIP) sequencing, with its induction linked to activation. Hypoxia increased the production of RASAL2-enriched extracellular vesicles (EVs) derived from tubular cells, which were internalized by endothelial cells, contributing to the exacerbation of PTC loss. These findings underscore RASAL2's role in mediating reduced angiogenesis in RIF and reveal a novel EV-mediated communication between hypoxic tubular- and endothelial cells, demonstrating a complex interplay between angiogenesis and fibrosis in CKD pathogenesis.

目的:探究血管免疫母细胞性T细胞淋巴瘤(AITL)的临床病理学特点.方法:分析102 例AITL的临床特点以及病理组织学、免疫表型及分子遗传学特征.结果:淋巴结结构被肿瘤细胞全部或部分破坏.高内皮小静脉(HEVs)形成分枝状结构网,其内可见肿瘤细胞、免疫母细胞、组织细胞、浆细胞、嗜酸粒细胞弥漫浸润或浸润于副皮质区.肿瘤细胞胞浆透亮,被滤泡树突细胞(FDC)网围绕.免疫组织化学染色结果显示,肿瘤细胞表达CD3(102/102)、CD4(93/102)、CD5(87/102),并且表达多个滤泡辅助T细胞相关标志物,如BCL6(79/102)、CD10(44/102)、PD1(75/102)、CXCL13(43/102)和诱导型共刺激因子(ICOS)(99/102).FDC标志物CD21 和CD23 染色,清晰地显示滤泡外增生的FDC网.NGS检测了40 例AITL病例,发现4 个特征性基因突变,即TET2(31/40)、DNMT3 A(9/40)、IDH2(18/40)和RHOA(23/40).结论:AITL的临床病理表现复杂,其诊断需要结合临床、组织病理学、免疫组织化学、分子遗传学作综合判断;相较于其他滤泡辅助T细胞标志物,ICOS更有助于AITL的诊断.

Renal interstitial fibrosis (RIF) is a key feature of progressive chronic kidney disease (CKD), characterized by tubular epithelial cell (TEC) hypoxia and peritubular capillary (PTC) rarefaction. However, the mechanisms underlying these processes remain poorly understood. To address this knowledge gap, we conducted a comparative transcriptome analysis of hypoxic and normoxic HK-2 cells, identifying 572 differentially expressed genes (DEGs). Subsequent Gene Ontology (GO), protein‒protein interaction (PPI) network, and hub gene analyses revealed significant enrichment of DEGs in the HIF-1 signaling pathway based on KEGG enrichment analysis. To further explore TEC modulation under hypoxic conditions, we performed chromatin immunoprecipitation (ChIP) sequencing targeting HIF-1α, identifying 2915 genes potentially regulated by HIF-1α. By comparing RNA sequencing and ChIP sequencing data, we identified 43 overlapping DEGs. By performing GO analysis and peak annotation with IGV, we identified two candidate molecules, VEGFA and BTG1, that are associated with angiogenesis and whose gene sequences were reliably bound by HIF-1α. Our study elucidates the molecular mechanisms underlying RIF, providing valuable insights for potential therapeutic interventions.

目的:探讨单形性亲上皮性肠道T细胞淋巴瘤(MEITL)的临床病理特征及巨核细胞相关酪氨酸激酶(MATK)表达的意义.方法:分析19例MEITL患者MEITL的病理组织形态学和免疫表型特点.结果:MEITL患者的肿瘤细胞小至中等大小,瘤细胞规则,核圆形,核仁不明显,胞质淡染.肿瘤细胞具有显著的亲上皮现象,缺乏炎症和坏死背景.肿瘤细胞表达CD3、CD8、CD56和TIA1,不表达CD5,EBER原位杂交均阴性.MATK高表达,阳性率超过80％.结论:MEITL是罕见的侵袭性原发性肠道T细胞淋巴瘤,诊断和鉴别诊断依赖于组织形态学和独特的免疫表型.MATK高表达有助于MEITL与其他肠道T细胞淋巴瘤的鉴别诊断.

目的:分析血管免疫母细胞性T细胞淋巴瘤(AITL)的临床病理特征,为临床上诊断该病提供依据.方法:选择南京市浦口区中心医院收治的11例AITL患者作为研究对象.对这些患者的临床病理资料进行回顾性分析,总结AITL的临床病理特征.结果:对11例AITL患者送检的淋巴结标本进行肉眼检查的结果显示,这些淋巴结均存在不同程度的增大,其长径为1～4.7 cm,均可见包膜存在.镜下检查可见个别淋巴结残存萎缩的生发中心,但大部分淋巴结的结构完全消失;部分标本存在明显的淋巴结包膜浸润现象,可见典型的肿瘤细胞弥漫浸润(为较小的淋巴样细胞弥漫浸润)、核膜存在和颜色较淡的胞质,肿胀的内皮细胞呈分枝状;背景可见反应性的小淋巴细胞、浆细胞、嗜酸性粒细胞、组织细胞增生,且滤泡树突状细胞增生明显,分布为网状.11例患者送检的淋巴结标本经免疫组化检查均可见CD3呈弥漫性表达,CD10、Bcl-6和CXCL13呈不同程度的表达,CD8和CD4呈混合性表达.结论:AITL的临床病理特征主要是淋巴结存在不同程度的增大、淋巴结包膜存在,镜检可见大部分淋巴结的结构完全消失及典型的肿瘤细胞弥漫浸润,进行免疫组化检查可见CD3呈弥漫性表达、CD10、Bcl-6和CXCL13呈不同程度的表达.

Abstract Introduction To evaluate the safety and efficacy of BTK inhibitor ibrutinib or zanubrutinib plus bendamustine and rituximab (iBR or zBR) as the initial treatment for chronic lymphocytic leukemia (CLL)/ small lymphocytic leukemia (SLL) patients, we conducted this single-arm retrospective observational study. Methods We enrolled patients over 18 years old with CLL/SLL who required treatment. iBR or zBR were administrated as following, ibrutinib 420 mg daily or zanubrutinib 160 mg twice daily from day 0, rituximab 375 mg/m 2 on day 0 of cycle 1 and 500 mg/m 2 on day 0 of cycle 2-6, bendamustine (70 mg/m 2, days 1-2), 28 days per cycle, ibrutinib or zanubrutinib was maintained at least 2 years and planned to discontinue in patients with undetectable minimal residual disease (uMRD) in both peripheral blood (PB) and bone marrow (BM). Response assessment was conducted after 3 cycles and 2 months after 6 cycles (EOT) according to 2018 iwCLL criteria in patients with CLL and 2014 Lugano criteria in patients with SLL. Minimal residual disease (MRD) in PB was detected after each cycle and MRD in BM was detected after 3 and 6 cycles by flow cytometry. uMRD was defined as less than 1 CLL cell per 10 4 leukocytes by flow cytometry. R esults At data cut-off (15 th June 2021), 10 treatment-naïve patients in the First Affiliated Hospital of Nanjing Medical University were enrolled, with 9 CLL and 1 SLL. All patients had completed planned six cycles of iBR(n=8) or zBR(n=2). The median age was 56 years old. Unmutated IGHV was detected in 30.0% (3/10) patients, one patient (1/8, 12.5%) had both del(17p) and TP53 mutation. Among 9 patients with CLL, 3 (33.3%) was classified as low-risk group according to CLL-IPI, 4(44.4%) in intermediate-risk, 1(11.1%) in high-risk group and 1(11.1%) in very-high risk group (Table 1). After 3 cycles, the overall response rate (ORR) was 100%, and complete remission (CR) rate was 20.0%, one patient achieved CRi (CR with incomplete bone marrow recovery). 50% (5/10) and 37.5% (3/8) patients achieved uMRD in PB and BM respectively. The ORR was 100% (10/10) and CR rate was 60.0%, 3 patients achieved CRi (30.0%) at EOT. 60.0% (6/10) and 50.0% (5/10) patients achieved uMRD in PB and BM respectively (Table 2, Figure 1). The most common hematological toxicity events were neutropenia and thrombocytopenia, and the non-hematological toxicity events were malaise, pruritus, nausea, vomiting and hematuria. The occurrence rate of grade 3 to 4 neutropenia and agranulocytic fever were 40.0% (4/10) and 10.0% (1/10) respectively. The most common ibrutinib-related AE were purpura, rash, diarrhea and hematuria. The occurrence rate of AE induced discontinued ibrutinib or zanubrutinib were 30.0% (3/10). Conclusion Here, we first reported the efficacy and tolerance of BTK inhibitor plus BR as initial treatment in a small cohort of CLL/SLL patients. BTK inhibitor plus BR could achieved high response rate and high proportion of undetectable MRD，with manageable toxicity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third-or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8-11 months in the West and 13-17 months in East Asia/ Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. Methods/Design: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). Discussion: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy.

Background: To evaluate the efficacy and safety of venetoclax, rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (VR-DA-EPOCH) in Richter's syndrome (RS), we conducted a single-arm, retrospective, observational, real-world study in our center.

Objectives: Sperm-associated antigen 5 (SPAG5), a spindle-binding protein, regulates the process of mitosis. The present study focused on the relationship between SPAG5 expression and the clinicopathological characteristics and prognosis of ovarian cancer. Methods: First, we used the Gene Expression Omnibus (GEO) database to analyze SPAG5 expression in ovarian cancer and its clinical relevance. Subsequently, qPCR test was used to detect SPAG5 mRNA expression in 20 cases of ovarian cancer. The expression of SPAG5 protein in a tissue microarray containing 102 cases of ovarian cancer was detected by immunohistochemistry. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for the 102 ovarian cancer patients. Results: In the GEO datasets, SPAG5 mRNA expression was significantly higher in ovarian cancer tissues than that in normal ovarian tissues (P < 0.001). qPCR and immunohistochemistry showed that SPAG5 expression in ovarian cancer tissues was significantly higher than that in paracancerous tissues (P = 0.002, P < 0.001). The high expression of SPAG5 in ovarian cancer was correlated with histological type (P = 0.009), lymph node metastasis (P = 0.001), distant metastasis (P = 0.001), TNM stage (P = 0.001), and prognosis (P = 0.001). The Kaplan-Meier curve indicated that rates of disease-free survival (DFS) and overall survival (OS) were even lower in patients with high SPAG5 expression. Multivariate analysis showed that SPAG5 expression (P = 0.001) and TNM staging (P = 0.002) were independent prognostic factors for the DFS of ovarian cancer. Conclusions: These results suggest that high SPAG5 expression was correlated with multiple clinicopathological features of ovarian cancer and can be used as an evaluation indicator for a poor ovarian cancer prognosis.

OBJECTIVECarbonic anhydrase XII (CA XII) is a key mediator of several signaling pathways that are involved in cancer development. This study was designed to investigate the clinical significance and prognostic value of postoperative CA XII expression in patients with hepatocellular carcinoma (HCC).METHODSImmunohistochemistry (IHC) was performed on HCC tissue (n = 90), and the relationships between CA XII expression in the HCC tissue, the clinicopathologic features, and survival were further evaluated. The mRNA expression of CA XII and clinicopathologic characteristics of patients with hepatocellular carcinoma were extracted from The Cancer Genome Atlas (TCGA) database.RESULTSCA XII was overexpressed in hepatocellular carcinoma tissues compared to normal liver tissues from the TCGA database. Moreover, CA XII mRNA expression was significantly associated with several clinicopathologic factors of hepatocellular carcinoma including sex (P = 0.011) and pathologic grade (P = 0.012). For HCC tissue samples in a tissue microarray (TMA), high CA XII protein expression was closely related to age (P = 0.013), tumor size (P = 0.014), and pathological grade (P = 0.015). A Kaplan-Meier analysis showed that elevated CA XII expression was associated with short disease-free survival (DFS) (P = 0.002) and overall survival (OS) (P = 0.006). In addition, a multivariate analysis showed that high CA XII expression was an independent prognostic indicator for disease-free survival (P = 0.018), but not overall survival, in HCC patients.CONCLUSIONThis study showed that high CA XII expression was associated with poor prognosis in HCC patients.

Objective Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients. Methods The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan–Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways. Results The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype. Conclusion Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.

OBJECTIVES The present study investigated the correlation between α B-crystallin (CRYAB, HSPB5) and p53 expression in ovarian cancer and further analyzed the relationship between their expression and clinicopathology and the prognostic value of their co-expression in ovarian cancer. METHODS CRYAB and p53 expression was assessed using immunohistochemistry on ovarian cancer tumor tissues from 103 cases and validated in an independent group of 103 ovarian cancer patients. RESULTS High CRYAB and p53 expression rates in ovarian cancer tissues were 61.17% (63/103) and 57.28% (59/103), respectively, and their expression was positively correlated (r = 0.525, P=0.000). High CRYAB expression was significantly correlated with tumor size (P=0.028), lymph node metastasis (P=0.000), distant metastasis (P=0.005), tumor node metastasis (TNM) stage (P=0.002), and survival (P=0.000), while high p53 expression was significantly correlated with tumor size (P=0.006), pathological grade (P=0.023), lymph node metastasis (P=0.001), and survival (P=0.000). Further studies found that the high CRYAB and p53 co-expression was also significantly correlated with pathological grade (P=0.024), lymph node metastasis (P=0.000), Distant metastasis (P=0.015), TNM stage (P=0.013), and survival (P=0.000). High expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were significantly correlated with poor disease-free survival (DFS) and overall survival (OS), respectively (P<0.05). Patients with high CRYAB and p53 co-expression had the worst prognoses among the groups. In addition, multivariate Cox regression models showed that high expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were independent prognostic factors for DFS and OS (P<0.05). Moreover, the positive correlation and prognostic value of CRYAB and p53 expression were verified in another independent dataset. CONCLUSIONS We demonstrated that patients with high CRYAB and p53 co-expression in ovarian cancer have significantly increased risks of recurrence, metastasis, and death compared with other patients. Therefore, more frequent follow-up of patients with high CRYAB and p53 co-expression is required. Our results also suggest that combination therapy with CRYAB inhibitors and p53 blockers may benefit future treatment of ovarian cancer patients with high co-expression of CRYAB and p53.

1Medical School, Southeast University, Nanjing, People’s Republic of China; 2Department of Liver Disease, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, People’s Republic of China; 3Department of Hematology and Oncology, Geriatric Hospital of Nanjing Medical University, Jiangsu Province Geriatric Hospital, Nanjing, People’s Republic of China; 4Department of Pathology, Pukou District Central Hospital, Pukou Branch of Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Pathology, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China

目的 探讨假肌源性血管内皮瘤(pseudomyogenic hemangioendothelioma,PHE)的临床病理特征、诊断及鉴别诊断.方法 回顾性分析3例PHE的临床病理特征、免疫表型、诊断及鉴别诊断、预后等,并复习相关文献.结果 3例患者,年龄38～70岁,中位年龄56岁,肿块平均直径4 cm,边界不清,浸润性生长.镜下见肿瘤细胞结节状生长,瘤细胞上皮样,卵圆形或梭形,大而肥胖,胞质嗜酸性,核仁小,核分裂罕见.免疫表型:肿瘤细胞表达CD31、Fli-1、CK(AE1/AE3),不表达S-100、desmin、SMA.结论 PHE是一种少见的软组织肿瘤,需与上皮样肉瘤、上皮样血管内皮瘤、上皮样血管肉瘤等肿瘤鉴别.

Purpose Although MAGEC2 was first cloned from a human hepatocellular carcinoma (HCC) cDNA library by serum screening, the detailed attributes of MAGEC2 in HCC have rarely been elucidated. Patients and methods In this study, The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were consulted to analyse the expression of MAGEC2 mRNA in liver cancer. Immunohistochemistry (IHC) analysis was performed to detect MAGEC2 expression in HCC, and the relationship between MAGEC2 expression and the clinicopathological characteristics of HCC patients was evaluated. Then, we employed the short hairpin (sh)RNA-mediated knockdown of MAGEC2 in HCC cell lines to explore the function of MAGEC2 in HCC development. Finally, the expression of epithelial-mesenchymal transition (EMT) markers in HCC xenografts and clinical samples was investigated. Results The results showed a remarkably higher level of MAGEC2 expression in HCC tissues than in noncancerous tissues, and MAGEC2 expression could be used as an independent prognostic factor for overall survival in HCC. Moreover, sh-MAGEC2 inhibited a series of HCC malignant behaviours both in vitro and in vivo. Finally, decreased MAGEC2 expression and low levels of EMT markers were detected in sh-MAGEC2 xenografts, while increased MAGEC2 expression and high levels of EMT markers were observed in invasive and metastatic HCC samples. Conclusion Taken together, our data imply that MAGEC2 is a novel prognostic marker for HCC and that MAGEC2 significantly promotes HCC tumourigenesis by inducing EMT. Targeting MAGEC2 may provide a promising therapeutic strategy for HCC treatment.

Renal cell carcinoma (RCC) is characterized by excessive angiogenesis, while chronic kidney disease (CKD) suffers from the opposite problemfailure of reparative angiogenesis. It can be due to their different responses to hypoxic environment. But the specific molecular regulators are still unclear. This study is aimed to explore the influence of human renal cell cancer cells (786-0) and human renal tubular epithelial cells (HK-2) on RECK expression, proliferation, and angiogenesis of adjacent microvascular endothelial cells (HMEC-1) under chemical hypoxia. Cobalt chloride (CoCl2) treatment was used to simulate the hypoxia environment in RCC and CKD. Co-culture, cell proliferation assay, and tube formation assay were used to evaluate the influence of 786-0 or HK-2 cells on proliferation and angiogenesis of adjacent HMEC-1 cells. Effects of different environments on RECK expressions in 786-0, HK2, or HMEC-1 cells were determined by Western blot. We found that both 786-0 cells and HK2 cells can upregulate RECK expression of adjacent HMEC-1 cells in normoxic conditions. However, under hypoxia, the HMEC-1 cells co-cultured with 786-0 significantly reduced RECK expression and there was no significant change in HMEC-1 cells co-cultured with HK2 cells. We also found that 786-0 significantly enhanced the proliferation and angiogenesis of adjacent HMEC-1 cells. Our results suggested that some paracrine substances produced by 786-0 cells may reduce RECK expression of adjacent HMEC-1 cells and enhance their proliferation and in vitro angiogenic capacity.