The extracellular secretion of miR-1825 wrapped by exosomes increases CLEC5A expression:A potential oncogenic mechanism in ovarian cancer

Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further probed.Methods:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)data.Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out.The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves.The CLEC5A expression pattern in OC was validated using immunohistochemistry.The CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO cohort.Finally,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also compared.Results:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor.The CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in it.While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was lower.Conclusion:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.

Immune checkpoint inhibitor-associated gastritis:Patterns and management

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of ICIs.Although irAE gastritis is rarely reported,it may lead to serious complications such as gastrorrhagia.Furthermore,irAE gastritis is often difficult to identify early due to its diverse symptoms.Although steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains uncertain.In addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered.In this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

癌症患者癌因性疲乏、生活质量和疼痛程度的相关性研究

目的分析癌症患者疼痛程度、疲劳程度与生活质量之间的关系。方法采用横断面研究设计。应用便利抽样法于2019年5-11月选取两省两所三级甲等医院224例接受化疗且符合入选标准的癌症患者进行调查。采用一般资料调查表、简明疲劳量表(Brief Fatigue Inventory,BFI)、疼痛数字评分量表(The Nume-rical Rating Scale,NRS)和由欧洲癌症治疗和研究组织编制的生活质量量表(The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire,EORTCQLQ-C30)收集资料。结果在报告过去24 h最严重的疼痛情况时,85例(37.9%)有轻度疼痛,121例(54.0%)有中度疼痛,18例(8.0%)有重度疼痛。此外,92例(41.1%)患者有轻度疲劳,72例(32.1%)有中度疲劳,60例(26.8%)有重度疲劳。大多数轻度疼痛的患者仅经历轻度疲劳,其生活质量也处于中等水平。中度和重度疼痛患者大多有中度或更高程度的疲劳(r=0.296,P<0.01)和较低的生活质量(r=-0.141,P<0.01)。轻度疼痛患者中,疲劳与生活质量间不存在相关性(r=-0.179,P=0.104)。中、重度疼痛患者的疲劳与生活质量呈负相关(r=-0.537,P<0.01;r=-0.509,P<0.05)。结论中、重度疼痛患者的疲劳症状比轻度疼痛患者更重,生活质量也更低。护士应更关注中重度疼痛患者,探索症状间的相互作用机制,开展症状联合干预,以提高患者生活质量。

Mitophagy-related gene signature predicts prognosis,immune infiltration and chemotherapy sensitivity in colorectal cancer

BACKGROUND Mitophagy plays essential role in the development and progression of colorectal cancer(CRC). However, the effect of mitophagy-related genes in CRC remains largely unknown.AIM To develop a mitophagy-related gene signature to predict the survival, immune infiltration and chemotherapy response of CRC patients.METHODS Non-negative matrix factorization was used to cluster CRC patients from Gene Expression Omnibus database(GSE39582, GSE17536, and GSE37892) based on mitophagy-related gene expression. The CIBERSORT method was applied for the evaluation of the relative infiltration levels of immune cell types. The performance signature in predicting chemotherapeutic sensitivity was generated using data from the Genomics of Drug Sensitivity in Cancer database.RESULTS Three clusters with different clinicopathological features and prognosis were identified. Higher enrichment of activated B cells and CD4+ T cells were observed in cluster Ⅲ patients with the most favorable prognosis. Next, a risk model based on mitophagy-related genes was developed. Patients in training and validation sets were categorized into low-risk and highrisk subgroups. Low risk patients showed significantly better prognosis, higher enrichment of immune activating cells and greater response to chemotherapy(oxaliplatin, irinotecan, and 5-fluorouracil) compared to high-risk patients. Further experiments identified CXCL3 as novel regulator of cell proliferation and mitophagy.CONCLUSION We revealed the biological roles of mitophagy-related genes in the immune infiltration, and its ability to predict patients’ prognosis and response to chemotherapy in CRC. These interesting findings would provide new insight into the therapeutic management of CRC patients.

Examined lymph node count for gastric cancer patients after curative surgery

Lymph node(LN)metastasis is the most common form of metastasis in gastric cancer(GC).The status and stage of LN metastasis are important indicators that reflect the progress of GC.The number of LN metastases is still the most effective index to evaluate the prognosis of patients in all stages of LN metastasis.Examined LN(ELN)count refers to the number of LNs harvested from specimens by curative gastrectomy for pathological examination.This review summarizes the factors that influence ELN count,including individual and tumor factors,intraoperative dissection factors,postoperative sorting factors,and pathological examination factors.Different ELN counts will lead to prognosis-related stage migration.Fine LN sorting and regional LN sorting are the two most important LN sorting technologies.The most direct and effective way to harvest a large number of LNs is for surgeons to perform in vitro fine LN sorting.

Rs3746444 T>C locus in miR-499 increases the susceptibility to hepatocellular carcinoma:A meta-analysis 14812 subjects

BACKGROUND Recently,many investigations have suggested that the rs3746444 T>C locus in the microRNA(miR)-499 gene may contribute to the occurrence of cancer.However,reports on the association between rs3746444 and hepatocellular carcinoma(HCC)are conflicting.AIM To further understand and explore the potential correlation between the singlenucleotide polymorphism of rs3746444 and the incidence of HCC.METHODS In this meta-analysis,we obtained electronic literature by searching the PubMed,Embase and Chinese BioMedical Disc databases(through May 20,2022).All eligible case-control,prospective cohort or nested case-control studies with sufficient data for calculating the odds ratios with their 95%confidence intervals were included.RESULTS Ultimately,a total of 17 independent studies were included.We identified that rs3746444 was associated with the development of HCC(C vs T:P=0.019 and CC/CT vs TT:P=0.016).In Asian individuals,rs3746444 was associated with susceptibility to HCC(C vs T:P=0.013 and CC/CT vs TT:P=0.016).In addition,this study identified that the miR-499 rs3746444 locus was associated with susceptibility to HCC in the normal/healthy control subgroup(C vs T:P=0.034 and CC/CT vs TT:P=0.024).CONCLUSION In summary,this meta-analysis highlights that rs3746444 in the miR-499 gene is involved in the occurrence of HCC,especially in Asian individuals.

Modified endoscopic submucosal tunnel dissection for large esophageal submucosal gland duct adenoma: A case report

BACKGROUND With the recent improvement of endoscopic techniques,endoscopic ultrasoundguided fine needle aspiration and endoscopic submucosal tunnel dissection(ESTD)have been widely used for accurate diagnosis and dissection acceleration of esophageal tumors.CASE SUMMARY We used a modified submucosal tunnel technique during endoscopic en bloc resection in a 58-year-old man with large esophageal submucosal gland duct adenoma(ESGDA).During modified ESTD,the oral end of the involved mucosa was cut transversely,followed by a submucosal tunnel created from the proximal to the distal end,and the anal end of the involved mucosa blocked by the tumor was incised.As a result of retaining submucosal injection solutions using the submucosal tunnel technique,it was possible to reduce the amount of injection required and increase the efficiency and safety of dissection.CONCLUSION Modified ESTD is an effective treatment strategy for large ESGDAs.Single-tunnel ESTD appears to be a time-saving procedure compared with conventional endoscopic submucosal dissection.

Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin,a novel humanized anti-HER2 antibody-drug conjugate therapy

Dear Editor,Extramammary Paget disease(EMPD)is a rare adenocarcinoma that originates in the apocrine gland-rich skin and usually affects the perineal skin(primary EMPD)or represents the intraepithelial spread of an underlying visceral carcinoma(secondary EMPD).Approximately half of EMPD cases are confined to the epidermis,which was defined as intraepithelial EMPD.

Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy.Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses.Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that our model effectively predicted the response of patients to immune-based treatments.Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Combining urine surface-enhanced Raman spectroscopy with PCA-SVM algorithm for improving the identification of colorectal cancer at different stages

Cancer staging detection is important for clinician to assess the patients' status and make optimal therapy decision. In this study, the machine learning algorithm based on principal component analysis(PCA) and support vector machine(SVM) was combined with urine surface-enhanced Raman scattering(SERS) spectroscopy for improving the identification of colorectal cancer(CRC) at early and advanced stages. Two discriminant methods, linear discriminant analysis(LDA) and SVM were compared, and the results indicated that the diagnostic accuracy of SVM(93.65%) was superior to that of LDA(80.95%). This exploratory study demonstrated the great promise of urine SERS spectra along with PCA-SVM for facilitating more accurate detection of CRC at different stages.

Revealing the roles of TLR7, a nucleic acid sensor for COVID-19 in pan-cancer

Recent studies suggested that cancer was a risk factor for coronavirus disease 2019 (COVID-19). Toll-like receptor 7 (TLR7), a severe acute respiratory syndrome 2 (SARS-CoV-2) virus’’s nucleic acid sensor, was discovered to be aberrantly expressed in many types of cancers. However, its expression pattern across cancers and association with COVID-19 has not been systematically studied. In this study, we proposed a computational framework to comprehensively study the roles of TLR7 in COVID-19 and pan-cancers at genetic, gene expression, protein, epigenetic, and single-cell levels. We found TLR7 mRNA expression was significantly up-regulated in 6 cancer types and down-regulated in 6 cancer types, further validated in the HPA database at the protein level. The genes significantly co-expressed with TLR7 were mainly enriched in the toll-like receptor signaling pathway, endolysosome, and signaling pattern recognition receptor activity. In addition, the abnormal TLR7 expression was associated with Mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB) in various cancers. Mined by the ESTIMATE algorithm, the expression of TLR7 was also closely linked to various immune infiltration patterns in pan-cancer, and TLR7 was mainly enriched in macrophages, as revealed by single-cell RNA sequencing. Finally, TLR7 expressions were very sensitive to a few targeted drugs, such as Alectinib and Imiquimod. In conclusion, TLR7 might be essential in the pathogenesis of COVID-19 and cancers.

Role of mitophagy in head and neck squamous cell carcinoma:Prognosis and immune insights

Objective:To explore the correlation between mitophagy and the tumor microenvironment(TME)in patients with head and neck squamous cell carcinoma(HNSCC),with an aim to enhance therapeutic efficacy for HNSCC.Methods:A machine learning-based multigene prognostic signature was developed based on mitophagy-related differentially expressed genes(MRGs)identified in The Cancer Genome Atlas cohort.This signature was correlated with the TME using gene set enrichment analysis.The association between this prognostic signature and various immunological features of the TME was explored,including status of tumor-infiltrating immune cells,expression of immune checkpoint molecules,and the immunoscore.Immunohistochemistry validated the expression of hub gene CSNK2A2 and assessed its relationship with immunomarker expression.Quantitative PCR validated CSNK2A2 knockdown in HNSCC cell lines.Functional experiments including Transwell assays to determine cell migration and invasion,Cell Counting Kit 8 assay,and 5-ethynyl-2-deoxyuridine assay were performed to confirm the role of CSNK2A2 in HNSCC.Finally,a subcutaneous xenograft model was generated in C3H mice to validate our findings.Results:The MRG-based prognostic signature showed excellent predictive performance.High-risk patients had significantly shorter progression-free and overall survival(P<0.0001)than low-risk patients.CD8+T cell infiltration was lower in high-risk groups,whereas low-risk groups showed higher immunological marker expression.Thus,the low-risk HNSCC subtype may benefit from immune therapy,while high-risk subtypes may benefit from chemotherapy(P<0.001).CSNK2A2 was highly expressed and strongly correlated with CD8 and PD-L1 based on immunohistochemistry of the HNSCC tissue microarray.CSNK2A2 knockdown reduced cell migration,invasion,and proliferation,and arrested cells in G1 phase.In vivo,it led to slower tumor growth and smaller tumor volumes.Conclusion:We established a potential prognostic signature that could improve HNSCC management in the future.CSNK2A2 may be a new biomarker to predict immunotherapy efficacy in HNSCC.

Hepatocellular carcinoma mutation landscape and its differences between Asians and Whites

Hepatocellular carcinoma(HCC)is one of the most common malignancies around the world and accounts for 85%to 90%of the pathological types of primary liver cancer(1).In total,905,677 patients die from HCC,which was the third leading cause of cancer-related death worldwide in 2020(2).Despite significant advancements achieved in early detection,liver transplantation,surgical technique,and local and systemic treatment,the overall prognosis of HCC remains dismal with a 5-year relative survival rate of 18.4%(3).