Although accumulating data have suggested the development of cancer in systemic lupus erythematosus (SLE) patients, these results remain inconsistent. To examine such a putative association, this analysis reports the association between SLE and the risks of 24 cancer types. Online databases PubMed, EMBASE, and Web of Science were searched comprehensively for eligible studies, published up to 15 May 2018. Pooled standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were utilized to reveal their associations. A total of 24 eligible studies were ultimately enrolled. Our results indicated that SLE was associated with increased risk of overall cancers, cancer risk in both genders, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, leukemia, multiple myeloma, cervix, vagina/vulva, renal, bladder, esophagus, gastric, hepatobiliary, lung, oropharynx, larynx, non-melanoma skin, and thyroid cancers. Additionally, SLE could reduce the risk of prostate cancer and cutaneous melanoma; however, it was not significantly associated with breast, uterus, ovarian, pancreatic, colorectal, or brain cancers. Our results shed light SLE being correlated with increased risk for 16 involved cancers and decreased risk for prostate cancer and cutaneous melanoma. This comprehensive meta-analysis provides epidemiological evidence supporting the associations between SLE and cancer risk. This evidence could be utilized to drive public policies and to help guide personalized medicine to better manage SLE and reduce associated cancer morbidity and mortality.

Background: It is well known that chronic inflammation can promote the occurrence and progression of cancer. As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in clear cell renal cell carcinoma (ccRCC) remains unclear.Methods: The transcriptome expression profile and mutation profile data of ccRCC with clinical characteristics included in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus clustering was used for clustering. Gene set enrichment analysis (GSEA) analysis were applied to evaluate the biological mechanisms. Single sample gene set enrichment analysis (ssGSEA) was applied for evaluating the proportion of various immune infiltrating cells. The ESTIMATE algorithm was involved to compute the immune microenvironment scores.Results: Among the 17 pyroptosis regulators, a total of 15 pyroptosis regulators were differential expressed between tumor and normal tissues, in which 12 of them emerged strong correlations with prognoses. According to the pyroptosis components, the ccRCC patients were divided into four pyroptosis subtypes with different clinical, molecular, and pathway characteristics. Compared with other clusters, cluster B showed the pyroptosis heat phenotype, while cluster D represented the pyroptosis cold phenotype with poor overall survival. In addition, we performed principal component analysis (PCA) on the differential genes between clusters to construct the pyroptosis index. Furthermore, the pyroptosis index was significantly correlated with survival in different tumor mutation statuses and different grades and stages. Besides, the expression of pyroptosis-related regulators was related to the infiltration of immune cells and the expression of immune checkpoints, among which AIM2 was considered as the most significant immune-related pyroptosis regulator. Ultimately, we found that AIM2 was related to the immune activation pathway and was significantly overexpressed in tumor tissues.Conclusion: This study revealed that pyroptosis regulators and pyroptosis index played an important role in the development and prognoses of ccRCC. Moreover, AIM2 can be used as a predictor of the response of immunotherapy. Assessing the pyroptosis patterns may help evaluate the tumor status and guide immunotherapy strategies.

Background: Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. Methods: According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. Results: Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. Conclusions: Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCA patients.

Galectin-3 as a β-galactoside-binding protein, has been found to be involved in tumor cell growth, anti-apoptosis, adhesion, angiogenesis, invasion, and distant metastases, indicating that it may play a pivotal role in cancer development and progression. However, their results remain debatable and inconclusive. Hence, this meta-analysis was performed to clarify the precise predictive value of galectin-3 in various cancers. PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wanfang databases were searched comprehensively for eligible studies up to July 15, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated to demonstrate their associations. A total of 36 relevant studies were ultimately enrolled in this meta-analysis. Our results shed light on the significant association of elevated galectin-3 expression with reduced OS or DFS/RFS/PFS in overall cancer patients (pooled HR = 1.79, 95% CI 1.42–2.27, I²= 67.3%, p < 0.01; pooled HR = 1.57, 95% CI 1.04–2.37, I²= 67.1%, p = 0.001). In tumor type subgroup analysis, we found high expression of galectin-3 was correlated with shorter OS or DFS/RFS/PFS in colorectal cancer (pooled HR = 3.05, 95% CI 2.13–4.35, I²= 0.0%, p = 0.734; pooled HR = 2.49, 95% CI 1.82–3.41, I² = 0.0%, p = 0.738; respectively) and meanwhile it merely associated with reduced OS in ovarian cancer or non-small cell lung cancer (pooled HR = 2.24, 95% CI 1.38–3.64, I²= 0.0%, p = 0.910; pooled HR = 2.07, 95% CI 1.48–2.88, I²= 0.0%, p = 0.563; separately). Taken together, our results suggested that galectin-3 played an oncogenic role in colorectal cancer, ovarian cancer and non-small cell lung cancer, indicating it could be a promising biomarker and a novel therapeutic target for them. Further studies were warranted to validate our findings.

Background: Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Also, increased expression of pro-inflammatory cytokines, or a “cytokine storm,” is associated with multiple organ dysfunction syndrome often observed in critically ill patients. Methods: We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially in specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2-specific signature. Results: Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were notably concentrated in endothelial cells, macrophages, spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging autoimmune mechanisms. Conclusion: This study provided new insights into the pathogenic mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.

STUDY QUESTION: Do testis-derived circular RNAs (circRNAs) in seminal plasma have potential as biomarkers to predict the outcome of microdissection testicular sperm extraction (micro-TESE) in patients with idiopathic non-obstructive azoospermia (NOA)?SUMMARY ANSWER: Testis-derived circRNAs in the seminal plasma can indeed be used for predicting the outcome of micro-TESE in patients with idiopathic NOA.WHAT IS KNOWN ALREADY: Micro-TESE is an effective method to obtain sperm samples from patients with idiopathic NOA. However, its success rate is only 40–50% in such patients.STUDY DESIGN, SIZE, DURATION: Six idiopathic NOA patients with different micro-TESE results were included as the discovery cohort. Their testicular tissues were used for extracting and sequencing circRNAs. Five circRNAs with the most significantly different expression levels were selected for further verification.PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifty-two patients with idiopathic NOA were included as the validation cohort. Preoperative seminal plasma samples of 52 patients with idiopathic NOA and 25 intraoperative testicular tissues were collected and divided into ‘success’ and ‘failure’ groups according to the results of micro-TESE. Quantitative real-time polymerase chain reaction was performed to verify differences in the expression levels of the selected circRNAs between the two groups in the testicular tissues and seminal plasma.MAIN RESULTS AND THE ROLE OF CHANCE: Whether at the seminal plasma or testicular tissue level, the differences in the expression levels of the three circRNAs (hsa_circ_0000277, hsa_circ_0060394 and hsa_circ_0007773) between the success and failure groups were consistent with the sequencing results. A diagnostic receiver operating curve (ROC) analysis of the AUC indicated excellent diagnostic performance of these circRNAs in seminal plasma in predicting the outcome of micro-TESE (AUC values: 0.920, 0.928 and 0.891, respectively). On the basis of least absolute shrinkage and selection operator (LASSO) logistic regression, the three circRNAs were combined to construct a new prediction model. The diagnostic ROC curve analysis of the model showed an AUC value of 0.958. The expression levels of these circRNAs in seminal plasma using three normospermic volunteer samples remained stable after 48 h at room temperature.LARGE SCALE DATA: NA.LIMITATIONS, REASONS FOR CAUTION: This was a single-center retrospective study with relatively few cases. The functions of these circRNAs, as well as their relationship with spermatogenesis, have not yet been established.WIDER IMPLICATIONS OF THE FINDINGS: Testis-derived circRNAs in seminal plasma can reflect the microenvironment of the testis and can be used as reliable biomarkers to screen patients with idiopathic NOA who might be suitable for micro-TESE.STUDY FUNDING/COMPETING INTEREST(S): This article was funded by the National Natural Science Foundation of China (Grant no. 81871151). There were no competing interests.