Prognostic Roles of N6-Methyladenosine METTL3 in Different Cancers: A System Review and Meta-Analysis.

BACKGROUND: Recent studies have shown that methyltransferase-like 3, a catalytic enzyme that is predominant in the N6-methyladenosine methyltransferase system, is abnormally expressed in various types of carcinoma and is correlated with poorer prognosis. However, the clinical functions of methyltransferase-like 3 in the prognosis of tumors are not fully understood. METHODS: We identified studies by searching PubMed, Web of Science, and MedRvix for literature (up to June 30, 2020), and collected a total of 9 studies with 1257 patients for this meta-analysis. The cancer types included gastric cancer, breast cancer, non-small cell lung cancer, bladder cancer, colorectal cancer and ovarian. We further used The Cancer Genome Atlas dataset to validate the results. RESULTS: High methyltransferase-like 3 expression clearly predicted a worse outcome (high vs. low methyltransferase-like 3 expression group; hazard ratio = 2.09, 95% confidence interval 1.53-2.89, P = 0.0001). Moreover, methyltransferase-like 3 expression was associated with differentiation (moderate + poor vs. well, pooled odds ratio = 1.76, 95% confidence interval 1.32-2.35, P = 0.0001), and gender (male vs. female, pooled odds ratio = 0.73, 95% confidence interval 0.55-0.97, P = 0.029). CONCLUSION: Our results suggest that methyltransferase-like 3 upregulation is significantly associated with poor prognosis and could potentially function as a tumor biomarker in cancer prognosis.

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis.

OBJECTIVE: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in multiple malignancies and associated with patients' prognosis, but its role in bladder cancer (BCa) remains elusive. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in BCa. METHODS: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and BCa pathological features. TCGA was mined for the information regarding as well. RESULTS: Our study included 14 articles enrolling 1398 people. Expression of HER2 is higher in bladder cancer than in normal tissues. HER2 over-expression is associated with CIS, multifocal tumor, large tumor size, high tumor stage and grade, lymph node metastasis, progression, recurrence and papillary tumor. We could not find a significant association between HER2 expression and survival time in BCa patients. CONCLUSIONS: Our meta and bioinformatic analysis indicated that HER2 expression was related to pathological malignancy and poor prognosis in BCa.

SP1 Expression and the Clinicopathological Features of Tumors: A Meta-Analysis and Bioinformatics Analysis.

Objective: Specificity protein 1 (SP1) plays a vital role to promote carcinogenesis in a variety of tumors, and its up-regulated expression is reported to be a hinter of poor prognosis of patients. We conducted this meta-analysis to elucidate the clinical significance and prognostic value of SP1 in malignant tumors. Methods: PubMed and Cochrane Library were searched for studies published between January 1, 2000 and June 1, 2020. The combined odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to investigate the correlation of SP1 with clinical behaviors and prognosis in patients with solid tumors. UALCAN was used to conduct bioinformatics analysis. Results: A total of 24 documents involving 2,739 patients were enrolled in our review. The random-effect model was used to perform this analysis due to the high level of heterogeneity. SP1 low expression was not conducive to lymph node metastasis (OR = 0.42; 95% CI: 0.28-0.64; p < 0.05), progression of TNM stage (OR = 0.34; 95% CI: 0.20-0.57; p < 0.05) and tumor infiltration (OR = 0.33; 95% CI: 0.18-0.60; p < 0.05). Elevated SP1 expression was connected with shorter survival time of patients with hepatocellular carcinoma, pancreatic cancer, gastric cancer and esophageal cancer (HR = 1.95; 95% CI: 1.16-3.28; p < 0.05). According to UALCAN database, breast cancer, ovarian cancer, colon cancer and lung adenocarcinoma display an elevated SP1 expression in comparison with normal tissues. Kaplan-Meier survival plots indicate SP1 mRNA level has negative effects on prognosis of liver hepatocellular carcinoma and brain lower grade glioma. Conclusion: SP1 was associated with lymph node metastasis, TNM stage and depth of invasion, and indicated poor clinical outcome, which brought new insights on the potential candidacy of SP1 in clinical usage.

SARS-CoV-2 effects in the genitourinary system and prospects of sex hormone therapy.

OBJECT: Corona virus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to acute respiratory infection symptoms. SARS-CoV-2 infection is not always limited to the respiratory tract, and renal infection and dysfunction have been shown to be specific risk factors for death. In addition, COVID-19 has a higher incidence, severity and mortality in men than women. This disparity is due to biological rather than comorbid or behavioral sex differences. Because the male reproductive system is unique, the function of sex hormones in COVID-19 infection may explain the differences between males and females. Understanding these factors will provide appropriate prevention measures and adequate triage strategies and guide the drug discovery process. METHODS: An electronic search was completed in PubMed, ARXIV, MEDRXIV and BIORXIV. The most relevant articles were systematically reviewed. In addition, single cell RNA sequencing analysis of tissue samples from human cell landscape was conducted. RESULTS: The influence of SARS-CoV-2 on the urogenital system, the possibility of urinary tract transmission and the functions of sex hormones were discussed in this review. CONCLUSION: Corona viruses can invade the genitourinary system, causing urological symptoms. Identifying the potential genitourinary organ impairments and protecting them from damage are necessary. Since sex hormones have potential as specific drugs, the gonadal hormones substitution therapy should be considered in both sexes in the COVID-19 pandemic.

Factors Associated with Survival From Xp11.2 Translocation Renal Cell Carcinoma Diagnosis-A Systematic Review and Pooled Analysis.

Purpose: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a rare subtype of renal cell carcinoma (RCC), characterized by translocations of Xp11.2 breakpoints, involving of the transcription factor three gene (TFE3). The aim of our study was to comprehensively characterize the clinical characteristics and outcomes, and to identify risk factors associated with OS and PFS in Xp11.2 tRCC patients. Methods: Literature search on Xp11.2 tRCC was performed using databases such as pubmed EMBASE and Web of Science. Studies were eligible if outcomes data (OS and/or PFS) were reported for patients with a histopathologically confirmed Xp11.2 tRCC. PFS and OS were evaluated using the univariable and multivariable Cox regression model. Results: There were 80 eligible publications, contributing 415 patients. In multivariable analyses, the T stage at presentation was significantly associated with PFS (HR: 3.87; 95% CI: 1.70 to 8.84; p = 0.001). The median time of PFS was 72 months. In the multivariable analyses, age at diagnosis (HR: 2.16; 95% CI: 1.03 to 4.50; p = 0.041), T stage at presentation (HR: 4.44; 95% CI: 2.16 to 9.09; p < 0.001) and metastasis status at presentation (HR: 2.67; 95% CI: 1.12 to 6.41; p = 0.027) were all associated with OS, with a median follow-up time of 198 months. Conclusion: T stage at presentation is the only factor that is associated with both PFS and OS in patients with Xp11.2 tRCC. Also, patients over 45 or with metastases are more likely to have poorer OS.