Long noncoding RNA VPS9D1-AS1 promotes the progression of endometrial cancer via regulation of the miR-187-3p/S100A4 axis.

VPS9D1-AS1 functions as an oncogene in many cancers. However, its role and potential mechanism in the progression of endometrial cancer (EC) are not fully understood. VPS9D1-AS1 levels in EC and adjacent normal tissues were investigated using the TCGA-UCEC cohort and 24 paired clinical samples. The roles of VPS9D1-AS1 and miR-187-3p in cell cycle, proliferation, and apoptosis were evaluated by loss- and gain-of-function experiments. In addition, the effect of VPS9D1-AS1 on tumor growth was further investigated in vivo. Rescue experiments were performed to investigate the involvement of the miR-187-3p/S100A4 axis in VPS9D1-AS1 knockdown-mediated antitumor effects. VPS9D1-AS1 was highly expressed in EC tissues. VPS9D1-AS1 knockdown, similar to miR-187-3p overexpression, significantly inhibited cell proliferation, inhibited colony formation, induced cell cycle arrest, and facilitated apoptosis of KLE cells. MiR-187-3p bound directly to VPS9D1-AS1 and the 3'UTR of S100A4. Furthermore, VPS9D1-AS1 negatively regulated miR-187-3p while positively regulating S100A4 expression in EC cells. MiR-187-3p knockdown or S100A4 overexpression partially reversed the tumor suppressive function of VPS9D1-AS1 knockdown. The results suggest that VPS9D1-AS1 affects EC progression by regulating the miR-187-3p/S100A4 axis. This may provide a promising therapeutic target to help treat EC.

Long-term risks of cardiovascular death among older patients with major hematological malignancies: a population-based cohort study from SEER database.

BACKGROUND: The objective of this study was to identify the risk of cardiovascular disease (CVD)-related death in older patients with major hematological malignancies (HM). METHODS: This study included 103,102 older patients diagnosed with 7 major types of HM between 1975 and 2018 (median follow-up: 2.7 years) from the Surveillance, Epidemiology, and End Result (SEER) database. The proportion of deaths, Fine-Gray sub-distribution hazards regression model, standardized mortality ratios (SMR) and absolute excess risk (AER) were used to evaluate the risk of CVD-related death. RESULTS: For older patients with HM, CVD-related death ranked as the second leading cause of death, surpassed only by primary malignancy. Compared to the general older population, older patients with HM had higher SMR and AER of CVD-related deaths (SMR: 1.16-1.81; AER: 41.24-308.99), heart disease-related deaths (SMR: 1.19-1.90; AER: 39.23-274.69), and cerebrovascular dis-ease-related deaths (SMR: 0.99-1.66; AER: -0.35 -24.15). The proportion of deaths and cumulative mortality increased with the passage of survival time, especially in Hodgkin lymphoma patients with stage I/II and those aged ≥85 years with chronic lymphocytic leukemia, surpassing primary malignancy. The risk of CVD-related death varied among different HM types. CONCLUSIONS: For older patients with HM, long-term cardiovascular risk management needs to be focused on while addressing the primary malignancy. IMPACT: Our results emphasize the need to manage long-term cardiovascular risk in older patients with HM, especially in those identified as high-risk cases.

The value of transitory protective stomas during primary debulking surgery for advanced epithelial ovarian cancer-- a retrospective cohort study.

OBJECTIVES: Limited data are available on patients with advanced-stage epithelial ovarian cancer (OC) who require ostomy during primary cytoreductive surgery. This study aimed to investigate the application of postoperative and long-term oncological results from transitory protective stoma (TPS) formation during primary debulking surgery (PDS) for OC. METHODS: This is a retrospective cohort study with a single center. We identified patients with stage III-IV OC who underwent colon resection and anastomosis. Depending on the methods used after colorectal anastomosis and the outcomes of surgical resection, the patients were stratified into three groups: resection and end-to-end anastomosis, resection and ostomy, or R1 resection. Demographic and clinical data were analyzed. RESULTS: 84 patients underwent colorectal resection during cytoreduction for FIGO stage III-IV OC. Patients undergoing ostomy were more likely to have a longer mean operative time (266 vs. 283 vs. 236 min; P=0.003) and to undergo rectosigmoid resection at the time of cytoreductive surgery (56.0% vs. 22.7%, P=0.007). Their postoperative feeding (7 vs. 1 vs. 3 d, P<0.001) and exhaustion (6 vs. 3 vs. 3, P<0.001) times were similar to those of patients with R1 resection and much earlier than those of patients with intestinal anastomosis. The first normal time (35 d) and half-life (14.68 d) of CA125 after surgery were significantly better in patients with TPS group. The overall incidence of complications was the same, and there was no significant difference in the 30-day readmission rate. The overall quality of life assessment was significantly lower in the R1 resection group. CONCLUSIONS: TPSs can accelerate postoperative recovery and the initiation of postoperative chemotherapy, reduce the risk of mortality and disease progression and limit the incidence of complications.

Analysis of clinicopathological features and prognosis of double primary cervical cancer and ovarian cancer based on SEER database.

OBJECTIVE: Double primary cervical cancer and ovarian cancer refer to the simultaneous or successive appearance of cervical cancer and ovarian cancer in the same patient. Due to the low incidence, there are few relevant reports. Therefore, this study is the first population-based analysis of the clinicopathological features as well as the prognostic status of double primary cervical cancer and ovarian cancer. We look forward to providing a reference for future clinical diagnosis and treatment. METHODS: In this study, 473 cases of double primary cervical cancer and ovarian cancer were collected from 1975 to 2019 through the SEER database. Double primary cancers were considered non-synchronous when they were diagnosed more than 6 months apart and were classified as Group A. Double primary cancers were considered synchronous when the interval between diagnosis of the two tumors was less than or equal to 6 months and was classified as group B. RESULTS: In this study, the incidence of double primary cervical cancer and ovarian cancer accounted for 0.39% of primary cervical cancer and 0.24% of primary ovarian cancer in the same period. 80% of patients developed second cancer within 107 months of their first cancer being diagnosed. Compared with non-synchronous cancer, synchronous cancer is mainly characterized by simultaneous bilateral ovarian involvement and early clinical stage, but highly malignant, high lymph node metastasis rate, and poor prognosis. CONCLUSION: Most patients developed second cancer within 107 months of their first cancer being diagnosed. Age at diagnosis, bilateral ovarian invasion, the interval between diagnoses, pathological type and stage of ovarian cancer, and grade of cervical cancer are important factors affecting survival, which still needs to be confirmed by more extensive studies in future.

OSR1 downregulation indicates an unfavorable prognosis and activates the NF-κB pathway in ovarian cancer.

BACKGROUND: Odd-skipped related 1 (OSR1) has been reported as a tumor suppressor gene in various malignant tumors. The mechanism through which OSR1 regulates ovarian cancer (OC) progression remains unclear. MATERIALS AND METHODS: Immunohistochemistry was utilized to evaluate OSR1 expression in patients with ovarian cancer. We investigated the association between clinicopathological parameters and OSR1 expression in OC patients and the influence of OSR1 expression on patient survival and prognosis. OC cells with OSR1 overexpression or knockdown were established and validated using Western blot and Quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The influence of OSR1 on the NF-κB pathway was examined by analyzing the p-IκBα, IκBα, p65, and p-p65 protein expression. In vitro assays, such as cell cycle assay, Cell Counting Kit-8 (CCK-8), transwell invasion assay, wound healing migration assay, enzyme-linked immunoassay (ELISA), and Annexin V/PI flow cytometry apoptosis assay, were conducted to explore the effect of OSR1 knockdown or dual inhibition of OSR1 and the NF-κB pathway on OC malignant biological behavior. RESULTS: OSR1 expression was downregulated in OC tissues, with significant associations observed between its expression and The International Federation of Gynecology and Obstetrics (FIGO) stage and tissue differentiation. Low OSR1 expression in OC patients correlated with reduced overall survival (OS) rates and poor prognosis. In vitro, experiments confirmed a negative correlation between OSR1 expression and NF-κB pathway activity. OSR1 knockdown facilitated OC cell malignant biological behavior, while the NF-κB pathway inhibitor (Bay 11-0782) reversed the impacts of OSR1 knockdown on cell proliferation, migration, invasion, and apoptosis. CONCLUSION: Our findings indicate that OSR1 is downregulated and associated with OC prognosis. OSR1 suppresses NF-κB pathway activity and inhibits OC progression by targeting the NF-κB pathway.

Salidroside affects the Th17/Treg cell balance in aplastic anemia via the STAT3/HIF-1α/RORγt pathway.

BACKGROUND: Acquired aplastic anemia (AA) is a life-threatening disease associated with an imbalance in Th17/Treg cells. Regulating this balance may be an effective treatment approach for AA. Rhodiola rosea has shown efficacy in AA treatment, but its mechanisms remain unclear. PURPOSE: We investigated salidroside's effect (a component of Rhodiola rosea) on Th17/Treg balance in adult AA patients and a mouse model. METHODS: HIF-1α mRNA and protein levels were measured in AA patients' peripheral blood. Flow cytometry, qRT-PCR, and WB analyzed salidroside's impact on T cell differentiation, Th17 cells, Treg cells, STAT3, HIF-1α, and RORγt expression. ELISA measured hematopoietic growth factors in mouse serum. RESULTS: AA patients exhibited elevated HIF-1α levels. Salidroside improved hematopoietic function, increasing blood cell count and enhancing bone marrow. Salidroside induced SCF, TPO, and IL-3 expression while inhibiting IL-2 in mice. Salidroside reduced STAT3, HIF-1α, RORγt, and IL-17a, while increasing FoxP3 expression, correcting the Th17/Treg imbalance in vitro and in vivo. CONCLUSION: Salidroside has potential as a novel AA treatment by correcting the Th17/Treg imbalance through the STAT3/HIF-1α/RORγt pathway.

CXCL10 and CCL5 as feasible biomarkers for immunotherapy of homologous recombination deficient ovarian cancer.

This study aims to identify biomarkers of ovarian cancer, specifically those tumors exhibiting homologous recombination deficiency (HRD), to contribute to the optimization of immunotherapy. We screened the differentially expressed genes coding for CXCL10 and CCL5 by analyzing the transcriptome data of patient with different HRD scores in the ovarian cancer cohort of the TCGA database and validated our results using pathological tissue sections. The cellular origin of CXCL10 and CCL5 were identified using the single-cell sequencing data extracted from the GEO database combined with the tumor mutational burden (TMB) and single nucleotide polymorphism (SNP) data obtained from the TCGA database. We found that CXCL10 and CCL5 expression levels were correlated with HRD score. Analysis of single-cell sequencing results and tumor mutation data suggested that both CXCL10 and CCL5 present in the tumor microenvironment were primarily derived from immune cells. In addition, we found that samples with high expression of CXCL10 and CCL5 also had higher stromal cell and immune cell scores, indicating low tumor homogeny. Further analysis showed that CXCL10 and CCL5 expression was associated with immune checkpoint-related genes, and the efficacy of using these proteins as biomarkers was significantly higher than that of PD-1 in predicting the effect of anti-PD-1 immunotherapy. The expression of CXCL10 and CCL5 had statistically different effects on the survival of patients, based on multivariate Cox regression. In summary, the results demonstrate that in ovarian cancer, the expression of CXCL10 and CCL5 are correlated with HRD. When CXCL10 and CCL5 are secreted by immune cells, immune cell infiltration can be chemotactic and predict the effect of immunotherapy more efficiently than using PD-1 as a biomarker. Therefore, CXCL10 and CCL5 look to be promising novel biomarkers to guide immunotherapy in ovarian cancer.

Pseudo-pseudo Meigs syndrome in systemic lupus erythematosus misdiagnosed as pseudo-Meigs' syndrome: A case report.

Symptoms of pelvic masses, elevated serum CA125 levels, massive ascites, and pleural effusion in female patients are usually associated with malignancy. Some benign ovarian tumors or other nonmalignant tumors may also produce similar symptoms, called Meigs syndrome or pseudo-Meigs' syndrome, which should be one of the differential diagnoses. However, there is an extremely rare form of SLE called pseudo-pseudo Meigs syndrome (PPMS), which may also present with the above symptoms, but is not associated with any of the tumors. In this paper, we report a case of a 47-year-old woman who presented with abdominal distention. The patient was found to have elevated serum CA125 levels to 182.9 U/mL before the operation. Her PET-CT suggested a large heterogeneous mass in the pelvis measuring 8.2 × 5.8 cm with a large amount of ascites. She was initially diagnosed with ovarian cancer and underwent exploratory laparotomy. Pathology of the surgical specimen revealed a uterine leiomyoma. Two months after discharge, the patient's ascites reappeared along with recurrent intestinal obstruction. After ascites and serological tests, she was eventually diagnosed with systemic lupus erythematosus and received systemic hormonal therapy.

Application and evaluation of transitory protective stoma in ovarian cancer surgery.

Ovarian cancer is the most fatal of all female reproductive cancers. The fatality rate of OC is the highest among gynecological malignant tumors, and cytoreductive surgery is a common surgical procedure for patients with advanced ovarian cancer. To achieve satisfactory tumor reduction, intraoperative bowel surgery is often involved. Intestinal anastomosis is the traditional way to restore intestinal continuity, but the higher rate of postoperative complications still cannot be ignored. Transitory protective stoma can reduce the severity of postoperative complications and traumatic stress reaction and provide the opportunity for conservative treatment. But there are also many problems, such as stoma-related complications and the impact on social psychology. Therefore, it is essential to select appropriate patients according to the indications for the transitory protective stoma, and a customized postoperative care plan is needed specifically for the stoma population.

Electro-acupuncture treatment inhibits the inflammatory response by regulating γδ T and Treg cells in ischemic stroke.

BACKGROUND: Electro-acupuncture (EA) is an effective and safe treatment for ischemic stroke. It is not only capable of reducing cerebral damage but also alleviating intestinal inflammation. However, its mechanism has not been fully elucidated. METHODS: All rats were randomly divided into three experimental groups: the SHAM group, the MCAO group, and the MEA (MCAO+EA) group. Ischemic-reperfusion (I/R) injury was induced by MCAO surgery. Rats in the MEA group were treated with EA stimulation in the "Baihui" acupoint (1 mA, 2/15 Hz, 20 min for each time). The Real-time (RT)-qPCR was used to evaluate the mRNA expression of inflammation factors in the ischemic brain and the small intestine after I/R injury. In addition, our research evaluated the effects of EA on regulatory T cells (Tregs) and γδ T cells in the small intestine and brain via Flow cytometry analysis. Finally, we applied CM-Dil and CFSE injection and explored the potential connections of T cells between the ischemic hemisphere and the small intestine. RESULTS: Our results suggested that EA treatment could significantly reduce the inflammation response in the ischemic brain and small intestine 3 days after I/R injury in rats. To be specific, EA increased the percentage of Tregs in the brain and the small intestine and decreased intestinal and cerebral γδ T cells. Concomitantly, after EA treatment, the percentage of cerebral CD3+TCRγδ+CFSE+ cells dropped from 12.06% to 6.52% compared with the MCAO group. CONCLUSIONS: These findings revealed that EA could regulate the Tregs and γδ T cells in the ischemic brain and the small intestine, which indicated its effect on inhibiting inflammation. And, EA could inhibit the mobilization of intestinal T cells, which may contribute to the protection of EA after ischemic stroke.

Effectiveness and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a systematic review and meta-analysis.

Background: Studies in recent years have shown that PD-1/PD-L1 inhibitors may have better effectiveness in patients with advanced or recurrent endometrial cancer. The effectiveness of PD-1/PD-L1 inhibitors is thought to be related to mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) classification in advanced or recurrent endometrial cancer. This study aims to evaluate the effectiveness of PD-1/PD-L1 inhibitors in patients classified as dMMR and pMMR. Methods: Medical databases were searched to identify relevant publications up to 30 November 2022. The primary outcome was comparison of objective response rate (ORR) in patients with dMMR and pMMR following treatment with PD-1/PD-L1 inhibitors; secondary outcomes were single-group ORR in patients with dMMR and in patients with pMMR, respectively. Results: Eleven studies were eligible for analysis and patients with advanced or recurrent endometrial cancer with molecular classification of dMMR had a higher total ORR than those with pMMR [odds ratio (OR), 7.70; 95% confidence interval (CI), 3.22-18.38; p < 0.01], with low evidence of between-study heterogeneity (I2 = 0%). The total ORR of patients with advanced or recurrent endometrial cancer with molecular type dMMR was 51.9% (95% CI, 33.6%-69.9%). The overall ORR of patients with advanced or recurrent endometrial cancer with molecular type pMMR was 16.1% (95% CI, 5.5%-30.3%). Conclusion: In our including studies, the patients with advanced or recurrent endometrial cancer with molecular types of dMMR and pMMR, following treatment with PD-1/PD-L1 inhibitors, the total ORR of patients with dMMR was higher than that of patients with pMMR. Since the current number of studies is not very large, it is possible that more studies will be published in the future and more precise results will be discussed further.

Corrigendum: Ubiquitin C-Terminal hydrolase L5 (UCHL5) accelerates the growth of endometrial cancer via activating the Wnt/ß-catenin signaling pathway.

[This corrects the article DOI: 10.3389/fonc.2020.00865.].

Identification of prognosis-related hub genes of ovarian cancer through bioinformatics analyses and experimental verification.

Ovarian cancer (OC) is a lethal and highly prevalent disease in women worldwide. The disease is often diagnosed in late stages, which leads to its rapid progression and low survival rate. This study aims to identify new prognostic genes for OC. Based on 2 datasets from the National Center for Biotechnology Information Gene Expression Omnibus public database, we constructed 2 Weighted Gene Co-expression Network Analysis networks. Then, we selected and intersected 2 key modules to screen key genes. Enrichment analyses were performed, and a protein-protein interaction network was constructed. The cytoHubba plugin of Cytoscape and survival analysis were used to screen hub genes related to prognosis. The expression of hub genes was analyzed by GEPIA and verified by quantitative Real-Time PCR. Gene alteration frequency analysis, gene set variation analysis, immune infiltration analysis, drug sensitivity analysis, tumor mutation burden, and neoantigen analyses were conducted to determine the prognostic value and molecular mechanisms of the hub genes. In total, 214 key genes were selected from 2 Weighted Gene Co-expression Network Analysis networks, and 3 hub genes, namely ALDH1A2, CLDN4, and GPR37, were identified as prognostic candidates through cytoHubba and survival analysis. Three hub genes were significantly associated with overall survival of OC patients. GEPIA and quantitative Real-Time PCR indicated that ALDH1A2 expression was significantly downregulated, while expression of CLDN4 and GPR37 was upregulated in OC samples compared with normal samples. CIBERSORT showed that 3 hub genes were closely associated with the infiltrating immune cells. GDSC showed that hub genes expression influenced IC50 values of chemotherapeutic drugs. OC patients with high expression of ALDH1A2 and CLDN4 had lower TMB and low ALDH1A2 expression could produce a larger number of neoantigens. In conclusion, the 3 hub genes (ALDH1A2, CLDN4 and GPR37) identified through bioinformatics analyses in the present study may serve as OC prognosis biomarkers. The study findings offer valuable insights into OC progression and mechanisms.

Odd-skipped related 1 plays a tumor suppressor role in ovarian cancer via promoting follistatin-like protein 1 transcription.

Zinc-finger transcription factor odd-skipped related 1 (OSR1) is involved in the progression of certain types of cancers, via regulating the transcription of downstream genes. However, the function of OSR1 in ovarian cancer (OC) progression remains unclear. The present study aimed to explore the OSR1 expression pattern in OC tissues and cell lines. Functional assays were performed to explore the regulatory effects of OSR1 on OC cell growth, migration and invasion in vitro and in vivo. Results of the present study demonstrated that OSR1 was significantly downregulated in OC tissues compared with healthy ovarian tissues (P < 0.01). Moreover, SKOV-3 and OVCAR-3 cells with low OSR1 expression were used for functional studies, and results demonstrated that OSR1 overexpression suppressed cell growth by inhibiting cell cycle progression and inducing cell apoptosis in vitro. OC cells with higher OSR1 expression levels exhibited reduced levels of migration and invasion, when compared with the corresponding control. In addition, OSR1 expression in xenografts models resulted in diminished tumor volume and suppressed tumorigenesis. OSR1 enhanced follistatin-like protein 1 (FSTL1) expression at the transcriptional level through directly binding to the promoter of FSTL1, which was commonly reported to exert a tumor suppressor role in OC progression. Moreover, FSTL1 knockdown reversed the action of OSR1 overexpression in OC progression, including cell viability, migration, invasion, and apoptosis. In conclusion, these results indicated that OSR1 may function as a tumor suppressor through augmenting FSTL1 transcription in OC progression, suggesting that the OSR1/ FSTL1 axis may exhibit potential as a therapeutic target for OC therapy.

Anti-Angiogenesis Maintenance Therapy in Newly Diagnosed and Relapsed Ovarian Cancer: A Meta-analysis of Phase III Randomized Controlled Trials.

Aim: Anti-angiogenesis agents have been added as maintenance therapy in ovarian cancer over the past decade. The aim of this meta-analysis was to analyze the efficacy of anti-angiogenesis therapy in newly diagnosed and relapsed ovarian cancer. Methods: PubMed, Embase, and Cochrane databases were searched for all phase III randomized controlled trials (RCTs) that assessed the efficacy and toxicity of anti-angiogenesis agents in ovarian cancer. Overall survival (OS) and progression-free survival (PFS) were used to evaluate the effectiveness of anti-angiogenesis therapy in ovarian cancer. Results: A total of 6097 patients with newly diagnosed ovarian cancer from 5 phase III RCTs and 2943 patients with relapsed ovarian cancer from 6 phase III RCTs were included in this meta-analysis. The pooled results showed that anti-angiogenesis maintenance therapy significantly improved PFS (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.76-0.93; p = 0.001), but not OS (HR, 0.98; 95% CI, 0.91-1.05; p = 0.49) compared with placebo in patients with newly diagnosed ovarian cancer. In patients with relapsed ovarian cancer, the pooled results showed a significant improvement on OS (HR, 0.89; 95% CI, 0.82-0.98; p = 0.02) and PFS (HR, 0.61; 95% CI, 0.52-0.72; p < 0.001). The pooled results also showed that the anti-angiogenesis agents were associated with an increase in the occurrence of severe hypertension, neutropenia, diarrhea, thrombocytopenia, headache, and bleeding in ovarian cancer. However, infrequent fatal adverse events occurred in the anti-angiogenesis groups. Conclusions: Study results suggest that anti-angiogenesis agents were an effective therapy for newly diagnosed and relapsed ovarian cancer, especially for relapsed ovarian cancer. Anti-angiogenesis agents may be associated with some severe but not fatal adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021283647.

Effects of methylenetetrahydrofolate reductase single-nucleotide polymorphisms on breast, cervical, ovarian, and endometrial cancer susceptibilities.

BACKGROUND: Recent studies identifying methylenetetrahydrofolate reductase (MTHFR) polymorphisms associated with breast cancer (BC), ovarian cancer (OC), cervical cancer, and endometrial cancer (EC) have reported conflicting results and been underpowered. To clarify the correlation between MTHFR mutations and these common female malignancies, we conducted a comprehensive meta-analysis incorporating all eligible publications. METHODS: Relevant reports published before January 20, 2020, were retrieved from PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure databases. The odds ratio and 95% confidence interval summaries for the MTHFR 677C/T and 1298A/C polymorphisms in BC, OC, cervical cancer, and EC were estimated. RESULTS: A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included. The results showed a markedly elevated risk of cancer susceptibility related to MTHFR 677C/T based on all genetic models. Similarly, we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models, except the heterozygous model. Moreover, subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models. Based on ethnicity, significant associations were observed between Asian, African, and mixed populations for 677C/T and the Asian population for 1298A/C. With regard to the sample type used for analysis, we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models. Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method, as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C, respectively. CONCLUSION: This meta-analysis suggests that MTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers, with these findings potentially applicable for overall comparisons of related data.

Identification of Claudin-6 as a Molecular Biomarker in Pan-Cancer Through Multiple Omics Integrative Analysis.

Claudin-6 (CLDN6) is one of the 27 family members of claudins and majorly involved in the tight junction and cell-to-cell adhesion of epithelial cell sheets, playing a significant role in cancer initiation and progression. To provide a more systematic and comprehensive dimension of identifying the diverse significance of CLDN6 in a variety of malignant tumors, we explored CLDN6 through multiple omics data integrative analysis, including gene expression level in pan-cancer and comparison of CLDN6 expression in different molecular subtypes and immune subtypes of pan-cancer, targeted protein, biological functions, molecular signatures, diagnostic value, and prognostic value in pan-cancer. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and further investigated CLDN6 from the perspective of the correlations with clinical characteristics, prognosis in different clinical subgroups, co-expression genes, and differentially expressed genes (DEGs), basing on discussing the validation of its established monoclonal antibody by immunohistochemical staining and semi-quantification reported in the previous study. As a result, CLDN6 expression differs significantly not only in most cancers but also in different molecular and immune subtypes of cancers. Besides, high accuracy in predicting cancers and notable correlations with prognosis of certain cancers suggest that CLDN6 might be a potential diagnostic and prognostic biomarker of cancers. Additionally, CLDN6 is identified to be significantly correlated with age, stage, weight, histological type, histologic grade, and menopause status in UCEC. Moreover, CLDN6 high expression can lead to a worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in UCEC, especially in different clinical subgroups of UCEC. Taken together, CLDN6 may be a remarkable molecular biomarker for diagnosis and prognosis in pan-cancer and an independent prognostic risk factor of UCEC, presenting to be a promising molecular target for cancer therapy.

Predictive Value of HE4 in Platinum-Based Chemotherapy for Ovarian Cancer: A Systematic Review.

OBJECTIVE: To evaluate the value of serum Human epididymis protein 4 (HE4) for predicting the resistance of ovarian cancer (OS) to platinum chemotherapy. METHOD: We searched the MEDLINE (PubMed), EMBASE, Cochrane Central, Web of Science, SCOPUS, and CNKI databases and screened all studies evaluating serum HE4 for predicting OC resistance to treatment with platinum. Two researchers independently evaluated the quality of all eligible original studies using QUADAS-2. RevMan 5.4 was used to compile the quality evaluation form. We also performed a meta-analysis with STATA15.1, and Deek's funnel plots were used to detect any publication bias. RESULTS: Eight studies were included in the final meta-analysis. Our results showed that the sensitivity and specificity of preoperative serum HE4 in predicting the resistance of OC to platinum chemotherapy was 80% and 67%, respectively. The diagnostic odds ratio was 8, and the AUC was 0.78 (95% CI: 0.75-0.82), whereas the pooled sensitivity and specificity of serum HE4 after the third-cycle of chemotherapies for predicting chemoresistance in OC was 86% and 85%, respectively, with a diagnostic odds ratio of 33 and AUC = 0.92 (95% CI: 0.89 - 0.94). CONCLUSION: HE4 may be an effective predictor of platinum-based chemotherapeutic resistance of OC. Serum HE4 levels after the third chemotherapy cycle may be indicative for clinical practice. Further research is needed to validate the significance of HE4 in the long-term management of OC. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021220099).

The role of YTH domain containing 2 in epigenetic modification and immune infiltration of pan-cancer.

YTH domain containing 2 (YTHDC2) is the largest N6-Methyladenosine (m6 A) binding protein of the YTH protein family and the only member containing ATP-dependent RNA helicase activity. For further analysing its biological role in epigenetic modification, we comprehensively explored YTHDC2 from gene expression, genetic alteration, protein-protein interaction (PPI) network, immune infiltration, diagnostic value and prognostic value in pan-cancer, using a series of databases and bioinformatic tools. We found that YTHDC2 with Missense mutation could cause a different prognosis in uterine corpus endometrial carcinoma (UCEC), and its different methylation level could lead to a totally various prognosis in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), lung squamous cell carcinoma (LUSC) and UCEC. The main molecular mechanisms of YTHDC2 focused on catalytic activity, helicase activity, snRNA binding, spliceosome and mRNA surveillance. Additionally, YTHDC2 was notably correlated with tumour immune infiltration. Moreover, YTHDC2 had a high diagnostic value for seven cancer types and a prognostic value for brain lower grade glioma (LGG), rectum adenocarcinoma (READ) and skin cutaneous melanoma (SKCM). Collectively, YTHDC2 plays a significant role in epigenetic modification and immune infiltration and maybe a potential biomarker for diagnosis and prognosis in certain cancers.