Background Spermidine (SPD) dysregulation is common in multiple cancers and is associated with reduced survival of cervical cancer (CC) cells. However, the mechanisms underlying SPD's role in CC progression remain poorly understood. This study aimed to investigate how SPD metabolism influences ferroptosis in cervical cancer. Methods Using bioinformatics analysis of public databases and immunohistochemistry on clinical specimens, we assessed the expression of SPD metabolic enzymes. In vitro experiments were conducted using HeLa and SiHa cervical cancer cell lines. Cell viability was measured by CCK-8 assay, mitochondrial morphology was observed via transmission electron microscopy, and protein expression was analyzed by Western blot. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were quantified using fluorescent probes and biochemical assays. Statistical significance was determined using Student’s t-test or one-way ANOVA. Results We identified elevated expression of the rate-limiting SPD metabolic enzyme SAT1 in cervical cancer tissues. SPD treatment induced ferroptosis in CC cells, as demonstrated by decreased Glutathione Peroxidase 4 (GPX4) expression, increased ROS and MDA levels, and characteristic mitochondrial alterations. Overexpression of SAT1 or supplementation with its downstream metabolite N 1 -acetylspermidine enhanced ferroptosis. Importantly, both SPD and N 1 -acetylspermidine attenuated the ferroptosis resistance caused by SAT1 inhibition. Conclusion Our findings reveal that enhanced SAT1-mediated SPD metabolism promotes ferroptosis in cervical cancer, suggesting that targeting this metabolic pathway could represent a novel therapeutic strategy for CC treatment.

Background The potential association between micro-/nanoplastics and cancer has raised increasing concerns. However, research focusing specifically on breast cancer (BC), and particularly on triple-negative breast cancer (TNBC), remains limited, leading to a critical gap in current knowledge. This study seeks to explore potential correlative effects of micro-/nanoplastic exposure on TNBC progression. Methods We employed scanning electron microscopy, micro-Raman spectroscopy, and pyrolysis–gas chromatography-mass spectrometry to characterize micro-/nanoplastics in BC tissues. Moreover, spatial transcriptomics (ST) analysis was applied to characterize putative molecular changes associated with polyethylene terephthalate (PET) micro-/nanoplastic exposure and TNBC progression, followed by in vitro and in vivo assays to further investigate these changes. Results A variety of micro-/nanoplastics were detected in human BC tissues. Among them, based on the results of the ST analysis, PET might be related to the downregulation of spermine/spermidine N1-acetyltransferase 1 (SAT1) in TNBC tumor cells and the inhibition of ferroptosis. Moreover, in vitro and in vivo data showed that, following PET treatment, SAT1 expression and ferroptosis were significantly downregulated, whereas TNBC cell proliferation and xenograft growth were significantly upregulated. Additionally, in vitro experiments further suggested that PET micro-/nanoplastics could interact with BC cells via particle endocytosis or surface adsorption. Conclusions This study suggests that SAT1-dependent ferroptosis may be a potential molecular pathway that links PET micro/nanoplastic exposure to TNBC progression. This finding provides novel insights into the possible toxicological association between micro-/nanoplastic exposure and TNBC progression.

Previous reports have indicated that placental trophoblast extracellular vesicles (EVs) possess unique properties that enable them significantly to inhibit the proliferation of ovarian cancer cells in vitro and slow ovarian tumour growth in an in vivo model, while EVs derived from monocytes did not. However, the mechanisms underlying the inhibitory effects of trophoblast EVs remain unclear. In this study, we characterized the microRNAs (miRNAs) uniquely present in placental trophoblast EVs but absent from THP-1 monocyte-derived EVs. Through bioinformatic analysis, we elucidated the potential involvement of these unique miRNAs in the negative regulation of proliferation pathways implicated in ovarian cancer. Functional assays demonstrated that placental trophoblast EVs inhibited ovarian cancer cell proliferation, and this effect was reversed upon blocking EV uptake, indicating the transfer of the contents of the EVs as a crucial mechanism modulating cancer cell viability. Using miRNA mimics, we also demonstrated that specific miRNAs from placental trophoblast EVs exhibited inhibitory effects on ovarian cancer cell proliferation, highlighting the potential of placental trophoblast EVs as therapeutic agents. These findings not only shed light on the molecular mechanisms underlying the therapeutic efficacy of placental trophoblast EVs but also provide valuable insights into the potential development of miRNA-based therapies for ovarian cancer, including the use of trophoblast EVs as a therapeutic for ovarian cancer.

Krukenberg tumours are rare metastatic ovarian tumour that originates primarily from the gastrointestinal tract. This study aimed to describe the diagnosis, treatment options, and survival outcomes in women with Krukenberg tumours treated in a single tertiary women’s hospital over a 16-year period. The case series included 15 patients diagnosed with Krukenberg tumours from 2008 to 2024. Data on pre-operative abdominal ultrasound and computed tomography scans, medical history, intraoperative history, treatment options, and laboratory parameters were collected from the hospital’s electronic database. None of the patients were preoperatively diagnosed with Krukenberg tumours, while 11 patients were suspected during surgery. Collaborating with gastroenterologists, oncologists, and pathologists confirmed these diagnoses as metastatic, with the primary sites identified. The other four patients with a history of gastrointestinal tumours (diagnosed 9 to 29 months prior) presented with gynaecological symptoms and were preoperatively diagnosed with primary ovarian tumours. However, Krukenberg tumours were confirmed intraoperatively in these cases as well. The primary tumour originated in the stomach for 10 patients and the colorectal region for 5 patients. Seven patients underwent cytoreductive surgery, while seven others underwent either a hysterectomy and bilateral salpingo-oophorectomy or bilateral salpingo-oophorectomy alone. One patient received palliative care. The median overall survival of all patients was 12 months, while the mean overall survival was 15 months. Among patients who underwent cytoreductive surgery, the median survival was 12.5 months, and the mean survival was 15 months. Pre-operative misdiagnosis of Krukenberg tumours is common. However, active collaboration with gastroenterologists, oncologists, and pathologists during surgery can help gynaecological oncologists overcome these diagnostic challenges.

Cervical cancer (CC) is a major health threat to women, with immunotherapies targeting the programmed death receptor 1/programmed death ligand 1(PD-1/PD-L1) axis showing promise but encountering resistance in a significant patient population. This resistance has driven a critical quest to uncover the underlying mechanisms. This study uncovers a novel metabolic axis involving the nicotinamide adenine dinucleotide (NAD+) salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) and the deacetylase Sirtuin 1 (SIRT1), which regulates PD-L1 expression and nuclear localization in CC. This axis may be a key factor contributing to the resistance observed in immunotherapy. This study reveals that PD-L1 overexpression in cancers is regulated by both transcriptional and post-transcriptional processes. Acetyl-proteomic analysis pinpoints SIRT1 as a central regulator in the deacetylation of histone H3 at lysines 27, which may influence PD-L1 subcellular distribution. This finding reveals the epigenetic control of immune checkpoint proteins by metabolic pathways, offering a new perspective on the regulation of PD-L1. The identification of the NAMPT/SIRT1 metabolic axis as a critical factor suggests that targeting this axis may enhance therapeutic responses.

BACKGROUND:5'-Nucleotidase Domain Containing 2 (NT5DC2), a member of the cNT5-II family that catalyzes nucleotide hydrolysis, plays a critical role in tumor initiation and progression. This study aims to elucidate the role of NT5DC2 across multiple cancers and to confirm its oncogenic significance in triple-negative breast cancer (TNBC). METHODS:NT5DC2 expression patterns were analyzed across multiple databases to evaluate its diagnostic and prognostic value in various cancers. Immune correlation analyses were performed using ESTIMATE and CIBERSORT algorithms. KEGG pathway enrichment analysis was used to explore NT5DC2-associated molecular pathways. In TNBC, comprehensive bioinformatics approaches, including gene expression profiling, single-cell RNA sequencing, immune infiltration analysis, and gene set enrichment analysis (GSEA), were employed. Additionally, in vitro experiments were conducted to validate the oncogenic role of NT5DC2 in TNBC. RESULTS:High NT5DC2 expression was associated with poor prognosis and demonstrated significant clinical diagnostic value across several cancer types. In TNBC, NT5DC2 was found to be highly expressed and correlated with adverse outcomes. Single-cell RNA sequencing revealed that NT5DC2 is predominantly expressed in epithelial cells and may regulate immune cell behavior through the MIF signaling pathway. Enrichment and immune infiltration analyses further indicated that NT5DC2 is strongly associated with an immunosuppressive tumor microenvironment (TME). In vitro experiments showed that NT5DC2 knockdown significantly suppressed TNBC cell growth, whereas its overexpression exerted opposing effects, highlighting its therapeutic potential. CONCLUSION:This study identifies NT5DC2 as an oncogene with broad clinical relevance across multiple cancers. In TNBC, NT5DC2 contributes to an immunosuppressive microenvironment and represents a promising diagnostic marker and therapeutic target.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC), characterized by limited treatment options and poor clinical outcomes. Aberrant FGFR signaling has been implicated in TNBC; however, the therapeutic potential of targeting FGFRs for TNBC treatment remains unclear. This study investigated the anti-cancer activity of the selective pan-FGFR inhibitor Erdafitinib and its underlying mechanisms using both in vitro and in vivo models. The results demonstrated that Erdafitinib suppressed TNBC tumorigenicity by promoting FGFR1/4 degradation, generating reactive oxygen species (ROS), inducing DNA damage, and ultimately triggering cell death. Mechanistic analyses revealed that Erdafitinib facilitated FGFR1/4 degradation through ubiquitination, enhanced interaction between TRIM25 and FGFR1/4, and subsequent lysosomal degradation. Furthermore, RNA-seq data from the TCGA and GEO databases, along with paired tumor tissues from TNBC patients, indicated that FGFR4 was significantly upregulated in TNBC. Notably, co-knockdown of FGFR1 and FGFR4 induced cytotoxicity in MDA-MB-231 cells, highlighting the therapeutic relevance of FGFR1/4 degradation by Erdafitinib in TNBC. These findings provide novel insights into the mechanisms underlying the anti-cancer efficacy of Erdafitinib, supporting its potential as a promising therapeutic agent for TNBC.

INTRODUCTION:Recurrent spontaneous abortion (RSA) is associated with maternal-fetal interface dysfunction, particularly abnormal trophoblast invasion and proliferation. However, our understanding of the cause of RSA remains limited. METHODS:Plasma Trp and Kyn levels were measured in two groups using enzyme-linked immunosorbent assay. Immunofluorescence and western blot analyses were employed to evaluate the expression of IDO1, VEGFA, and proteins associated with epithelial-mesenchymal transition (EMT) in villous and decidual tissues from patients with RSA. The effects of Tryptophan (Trp) and IDO1-driven Trp-Kynurenine (Kyn) metabolism on trophoblast proliferation, migration, EMT, and angiogenesis were investigated in the HTR-8/SVneo cell line using wound healing, transwell migration, quantitative real-time PCR (RT-qPCR), Western blotting, and tube formation assays. RNA sequencing (RNA-seq) identified differentially expressed genes in cells treated with 500 μM exogenous L-Trp. RESULTS:RSA patients exhibited elevated plasma Trp levels and significantly reduced Kyn levels, indicating decreased IDO1 activity (as assessed by the Kyn/Trp ratio) compared to controls. IDO1, EMT-related proteins, and VEGFA were downregulated in RSA patient tissues. In vitro, L-Trp enhanced trophoblast migration, invasion, EMT, and microvasculature formation via IDO1 activation. The reduced functional capabilities induced by the IDO1 antagonist 1-MT (500 μM) were rescued by Kyn (300 μM). RNA-seq revealed that L-Trp upregulation modulates trophoblast gene expression and functional pathways associated with amino acid metabolism, angiogenesis, and vasculature development. DISCUSSION:Our study reveals a novel molecular mechanism by which Trp metabolism regulates HTR-8 cell function, suggesting that modulating IDO1 activity may represent a therapeutic strategy to improve trophoblast function and pregnancy outcomes in RSA.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and severe cardiopulmonary disease with a challenging prognosis, and its underlying pathogenesis remains elusive. A comprehensive understanding of IPAH is crucial to unveil potential diagnostic markers and therapeutic targets. In this study, we investigated cellular heterogeneity and molecular pathology in IPAH using single-cell RNA sequencing (scRNA-seq) analysis. Our scRNA-seq results revealed significant alterations in three crucial signaling pathways in IPAH: the hypoxia pathway, TGF β pathway, and ROS pathway, primarily attributed to changes in gene expression within arterial endothelial cells. Moreover, through bulk RNA sequencing analysis, we identified differentially expressed genes (DEGs) enriched in GO and KEGG pathways, implicated in regulating cell adhesion and oxidative phosphorylation in IPAH lungs. Similarly, DEGs-enriched pathways in IPAH arterial endothelial cells were also identified. By integrating DEGs from three IPAH datasets and applying protein-protein interaction (PPI) analysis, we identified 12 candidate biomarkers. Subsequent validation in two additional PAH datasets led us to highlight five potential biomarkers (CTNNB1, MAPK3, ITGB1, HSP90AA1, and DDX5) with promising diagnostic significance for IPAH. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) confirmed significant differences in the expression of these five genes in pulmonary arterial endothelial cells from PAH mice. In conclusion, our findings shed light on the pivotal role of arterial endothelial cells in the development of IPAH. Furthermore, the integration of single-cell and bulk RNA sequencing datasets allowed us to pinpoint novel candidate biomarkers for the diagnosis of IPAH. This work opens up new avenues for research and potential therapeutic interventions in IPAH management.

BACKGROUND:Cervical cancer is a leading cause of death in developing countries. Although the placenta is a tumor-like organ, the placental development, including invasive function, is well controlled. One mechanism is that extracellular vesicles (EVs) released from the placenta contribute to this regulation. Placental EVs carry functional proteins and regulatory RNAs. Our previous study reported that placental EVs inhibited ovarian cancer growth in vitro and in vivo. METHODS:Whether the inhibitory effect induced by placental EVs also applies to cervical cancer, a non-endocrine-related cancer, in this study, we first co-cultured the cervical tumour tissues with placental explants. RESULTS:Co-culturing cervical tumour tissues (n = 7) with placental explants showed necrotic signs and increased levels of senescence-associated proteins and death-associated miRNAs, including miRNA-143-3p, miRNA-519a-5p and miRNA-199a-3p in tumour tissues. Additionally, treatment of HeLa cells with placental EVs reduced the viability of HeLa cells and inhibited the ability of invasion and migration of HeLa cells. Increased levels of senescence-associated proteins and reduced levels of proliferative proteins may contribute to the inhibitory effects in HeLa cells. DISCUSSION:placental EVs are involved in regulating placental development, and the delivery of cargo significantly impacts the functions of target cells. This study found that factors released from placental explants, likely placental EVs, had anti-tumour effects on the cervical tumour by inhibiting cervical cancer cell viability, invasion, and migration. Cargo in placental EVs, such as cellular death-associated miRNAs, may contribute to the inhibitory effects on cervical tumour.

Dietary selenium intake within the normal physiological range is critical for various supporting biological functions. However, the effect of nano-selenium on biological mechanism of goblet cells associated with autophagy is largely unknown.The purpose of this study was to investigate the effect of nano-selenium on the mucosal immune-defense mechanism of goblet cells (GCs) in the small intestine of laying hens.The autophagy was determined by using specific markers. Nano-selenium-treated group of immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) results indicated the strong positive immune signaling of microtubule-associated light chain (LC3) within the mucosal surface of the small intestine. However, weak expression of LC3 was observed in the 3-methyladenine autophagy inhibitor (3-MA) group. IHC and IF staining results showed the opposite tendency for LC3 of sequestosome 1 (P62/SQSTM1). P62/SQSTM1 showed strong positive immune signaling within the mucosal surface of the small intestine of the 3-MAgroup, and weak immune signaling of P62/SQSTM1 in the nano-selenium-treated group. Moreover, pinpointing autophagy was involved in the mucosal production and enrichment of mucosal immunity of the GCs. The morphology and ultrastructure evidence showed that the mucus secretion of GCs was significantly increased after nano-selenium treatment confirmed by light and transmission electron microscopy. Besides that, immunostaining of IHC, IF and WB showed that autophagy enhanced the secretion of Mucin2 (Muc2) protein in nano-selenium-treated group. This work illustrates that the nano-selenium particle might enhance the mucosal immune-defense mechanism via the protective role of GCs for intestinal homeostasis through autophagy.

INTRODUCTION:Placental extracellular vesicles (EVs), lipid-enclosed particles released from the placenta, can facilitate intercellular communication and are classified as micro- or nano-EVs depending on size. Placental EVs contain molecules associated with cell proliferation and death. In this study, we investigated whether treating human ovarian tumour explants with placental EVs could induce ovarian tumour cell death. METHODS:Human ovarian tumours were collected. After directly treating human ovarian tumour explants with placental EVs, cellular necrosis was observed in ovarian tumour explants by HE stains. Cell death-associated miRNAs were measured. RESULTS:Expression of apoptosis and senescence-associated proteins, including NF-κβ and γ H2AX, were significantly increased, while proliferation-associated proteins were significantly reduced in the explants after exposure to placental EVs. Furthermore, miRNA-519a-5p, miRNA-512-3p and miRNA-143-3p, which were reported to promote ovarian cancer cell apoptosis or inhibition of ovarian cancer cell growth, were significantly increased, and the target genes of miRNA-519a-5p and miRNA-512-3p were significantly reduced in the explants after exposure to placental EVs. Transfection of SK-OV-3 ovarian cancer cells with a mimic of miRNA-519a-5p or miRNA-143-3p reduced the viability of these cells. DISCUSSION:Our study demonstrated that placental EVs could induce necrosis in ovarian tumour explants. Increased levels of apoptosis and senescence-associated proteins and miRNAs could contribute to this change in ovarian tumour cell phenotype after exposure to placental EVs.

Introduction The overdiagnosing of papillary thyroid carcinoma (PTC) in China necessitates the development of an evidence-based diagnosis and prognosis strategy in line with precision medicine. A landscape of PTC in Chinese cohorts is needed to provide comprehensiveness. Methods 6 paired PTC samples were employed for whole-exome sequencing, RNA sequencing, and data-dependent acquisition mass spectrum analysis. Weighted gene co-expression network analysis and protein-protein interactions networks were used to screen for hub genes. Moreover, we verified the hub genes' diagnostic and prognostic potential using online databases. Logistic regression was employed to construct a diagnostic model, and we evaluated its efficacy and specificity based on TCGA-THCA and GEO datasets. Results The basic multiomics landscape of PTC among local patients were drawn. The similarities and differences were compared between the Chinese cohort and TCGA-THCA cohorts, including the identification of PNPLA5 as a driver gene in addition to BRAF mutation. Besides, we found 572 differentially expressed genes and 79 differentially expressed proteins. Through integrative analysis, we identified 17 hub genes for prognosis and diagnosis of PTC. Four of these genes, ABR, AHNAK2, GPX1, and TPO, were used to construct a diagnostic model with high accuracy, explicitly targeting PTC (AUC=0.969/0.959 in training/test sets). Discussion Multiomics analysis of the Chinese cohort demonstrated significant distinctions compared to TCGA-THCA cohorts, highlighting the unique genetic characteristics of Chinese individuals with PTC. The novel biomarkers, holding potential for diagnosis and prognosis of PTC, were identified. Furthermore, these biomarkers provide a valuable tool for precise medicine, especially for immunotherapeutic or nanomedicine based cancer therapy.

Topoisomerase II homologue 2 (PATL2) has been confirmed to be a key gene that contributes to oocyte maturation. However, the allele distribution and carrier frequency of these mutations remain uncharacterized. So a bioinformatics subcategory analysis of PATL2 mutations from outcome data and Single Nucleotide Polymorphism (SNP) databases was conducted. Altogether, the causative PATL2 mutation number detected in patients with oocyte maturation defects in the clinical studies and pathogenic PATL2 mutation sites predicted by software based on the database was approximately 53. The estimated carrier frequency of pathogenic mutation sites was at least 1.14‰ based on the gnomAD and ExAC database, which was approximately 1/877. The highest frequency of mutations detected in the independent patients was c.223-14_223-2del13. The carrier frequency of this mutation in the population was 0.25‰, which may be a potential threat to fertility. Estimated allele and carrier frequency are relatively higher than those predicted previously based on clinical ascertainment. A review of PATL2 mutation lineage identified in 34 patients showed that 53.81%, 9.22% and 14.72% of the oocytes with PATL2 mutations were arrested at the germinal vesicle (GV) stage, metaphase I (MI) stage and first polar body stage, respectively. Oocytes that could develop to the first polar body stage were extremely rare to fertilise, and their ultimate fate was early embryonic arrest. Phenotypic variability is related to the function of the regions and degree of loss of function of PATL2 protein. A 3D protein structure changes predicted by online tools, AlphaFold, showed aberrations at the mutation sites, which may explain partially the function loss. When the mutated and wild-type proteins are not in the same amino acid category, the protein structure will be considerably unstable. The integration of additional mutation sites with phenotypes is helpful in drawing a complete picture of the disease. Bioinformatics analysis of PATL2 mutations will help reveal molecular epidemiological characteristics and provide an important reference for new mutation assessment, genetic counselling and drug research.

目的 探讨卵巢Sertoli-Leydig细胞瘤(Sertoli-Leydig cell tumour,SLCT)的临床病理学特征、诊断、鉴别诊断、治疗及预后.方法 收集8例SLCT标本,观察大体及镜下特征,分析临床病理特点,行免疫组化方法检查,并复习相关文献.结果 8例患者平均发病年龄42.8岁,肿瘤均为单侧发生,右侧多见,多为实性或囊实性,可分泌雄激素,中-低分化者多见,病变局限于卵巢.免疫组化α-抑制素(α-inhibin)、广谱细胞角蛋白(CK-pan)、波形蛋白(Vimentin)、钙结合蛋白(Calretinin)、细胞表面糖蛋白99(CD99)、细胞表面金属肽链内切酶(CD10)、翼状螺旋/叉头转录因子2(FOXL2)、雌激素受体(ER)、雄激素受体(AR)均有较高阳性表达,细胞增殖标记(Ki-67)一般呈低表达,上皮细胞膜抗原(EMA)、甲胎蛋白(AFP)、嗜铬素A(CgA)、突触素(SYN)均为阴性,网染可见网状纤维围绕Sertoli细胞巢周围分布,AR在所有肿瘤中呈阳性表达,Sertoli细胞强于Leydig细胞.结论 SLCT发病率低,形态复杂,临床易误诊,确诊有赖于病理诊断和免疫组织化学染色,血清学雄激素的升高及免疫组化雄激素的表达对于诊断该肿瘤有一定指导意义,肿瘤的临床分期是评判肿瘤预后最有意义的指标,治疗采用以手术为主的综合措施.

Previous studies have shown that HE4 cancer biomarker promoted cancer cell proliferation and tumor growth in mouse xenograft models. Interestingly, HE4 levels are significantly increased in the seminal plasma of oligoasthenospermia patients, raising a question on HE4 role(s) in spermatogenesis. We constructed an HE4 overexpression mouse model (HE4-OE), and observed that HE4-OE male adult mice had small testes, low sperm counts, and elevated serum/testis testosterone levels. These mice exhibited disorganized seminiferous tubules and impaired spermatogenesis. HE4 overexpression concentrated in Leydig cells, and these cells had hyperplasia and increased testosterone biosynthesis. Mechanistic studies indicated that the impaired spermatogenesis was likely caused by a local and direct action of HE4 in the testis rather than by a hypothalamus/pituitary-initiated dysregulation. The new findings reveal a novel HE4 function in male reproductive system, and suggest the existence of a subtype of primary oligoasthenospermia characterized by HE4 overexpression, Leydig cell hyperplasia, and elevated testosterone levels.

Accumulated data indicated that many types of cancers have increased protein O-GlcNAcylation at cell surface and inside cells. The aberrant O-GlcNAcylation is considered a potential therapeutic target. Although several types of compounds capable of inhibiting O-GlcNAcylation have been developed, their low solubility, poor permeability and delivery efficiency have impeded the application for in vivo and pre-clinical studies. Nanocarriers have the advantages of controllable drug release and active cancer-targeting capability. Moreover, nanoparticles can improve drug delivery efficiency and reduce the non-specific distribution in normal tissues by the enhanced permeability and retention (EPR) effect in cancer. Taking the advantage of O-GlcNAc-specific antibodies or lectins, nanoparticles could further improve their cancer-targeting capability. Although nanocarriers targeting the canonical N- and O-linked glycosylation have been extensively investigated for cancer detection and therapy, application of nanotechniques for the specific targeting of O-GlcNAcylation has not been actively pursued. This review summarizes the general features of GlcNAcylation and its alterations in cancers. Analyses are focused on the following areas: How the nanocarriers may improve the solubility and/or cell permeability of O-GlcNAc transferase (OGT) inhibitors; The modification of nanocarriers with lectins or antibodies for active targeting of O-GlcNAc; The nanocarriers-mediated co-delivery of OGT inhibitors and conventional drugs, which may lead to synergistic effects. Unsolved issues impeding the research progression on O-GlcNAcylation-targeting scheme are also discussed.

Breast cancer (BRCA) is a complex disease that leads to major mortalities and unsatisfactory clinical outcomes among women worldwide. CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) is a potential tumor suppressor and regulator of PD-L1, which has been found as a functional signature in considerable oncogenesis, progression, and therapeutic resistance via deletion and downregulation. In this research, triple-negative breast cancer (BRCA), a molecular subtype having a lower response to endocrinotherapy but a higher response to chemotherapy and immunotherapy, showed higher transcriptional levels of CMTM7. Moreover, CMTM7 positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), and immune checkpoints in many independent datasets. Furthermore, in an immunotherapy cohort of BRCA, patients with high CMTM7 expression were more sensitive to immunotherapy, and the therapeutic predictive value of CMTM7 is higher than that of PD-1 and PD-L1. To sum up, CMTM7 correlated with an inflamed tumor microenvironment and identified immune-hot tumors, which can be a novel biomarker for the recognition of immunological characteristics and an immunotherapeutic response in BRCA.