Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity.

Renal cell carcinoma (RCC) is a common urologic disease. Currently, surgery is the primary treatment for renal cancer; immunotherapy is not as effective a treatment strategy as expected. Hence, understanding the mechanism in the tumor immune microenvironment (TME) and exploring novel immunotherapeutic targets are considered important. Recent studies have demonstrated that autophagy could affect the immune environment of renal cell carcinoma and induce proliferation and apoptosis of cancer cells. By comparing lysosomal genes and regulating autophagy genes, we identified the LAPTM4B gene to be related to RCC autophagy. By analyzing the TCGA-KIRC cohort using bioinformatics, we found M2 macrophages associated with tumor metastasis to be significantly increased in the immune microenvironment of patients with high expression of LAPTM4B. GO/KEGG/GSEA/GSVA results showed significant differences in tumor autophagy- and metastasis-related pathways. Single-cell sequencing was used to compare the expression of LAPTM4B in different cell types and obtain the differences in lysosomal and autophagy pathway activities in different ccRCC cells. Subsequently, we confirmed the differential expression of LAPTM4B in renal cell carcinoma of different Fuhrman grades using western blotting. Downregulation of LAPTM4B expression significantly reduced the proliferation of renal cell carcinoma cells and promoted cell apoptosis through cell experiments. Overall, our study demonstrated that the autophagy-related gene LAPTM4B plays a critical role in the TME of RCC, and suggested that LAPTM4B is a potential therapeutic target for RCC immunotherapy.

A comprehensive analysis of renal cell carcinoma as first and second primary cancers.

OBJECTIVE: Second primary renal cell carcinoma (2nd RCC) refers to renal cell carcinoma (RCC) diagnosed after another unrelated malignancy. This study aims to compare the clinical manifestation, pathology, treatment, and prognostic features of patients with 2nd RCC and first primary renal cell carcinoma (1st RCC). MATERIALS AND METHODS: Data of the patients with localized RCC were retrospectively collected. They were classified as 2nd RCC or 1st RCC according to a previously diagnosed cancer, including 113 cases of 2nd RCC and 749 cases of 1st RCC. RESULTS: The most common types of extrarenal malignancies in patients with 2nd RCC include lung, colorectal, breast, gynecological, and gastric cancers. The age and smoking rate of 2nd RCC patients were significantly higher than in those of 1st RCC patients. For 2nd RCC patients, fewer had clinical symptoms and renal masses tend to be smaller. One hundred and eight (95.6%) patients with 2nd RCC received surgical interventions. All patients with 1st RCC underwent renal surgery. More patients with 2nd RCC underwent a partial nephrectomy. Pathologically, there was no significant difference in postoperative pathological types between the 2nd and 1st RCCs. However, the 2nd RCCs were commonly identified in the early stages. The median overall survival (OS) of 2nd RCC patients was 117 months, which was shorter than that of 1st RCC patients. CONCLUSIONS: Second RCC is not uncommon. More attention should be paid to screening for 2nd RCC in cancer survivors. There are some differences between patients with 2nd and 1st RCCs that should be viewed separately.

Urinary Exosomes Diagnosis of Urological Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: Exosomes could be released directly into the urine by the urological tumoral cells, so testing urinary exosomes has great potential for non-invasive diagnosis and monitor of urological tumors. The objective of this study is to systematically review and meta-analysis of urinary exosome for urological tumors diagnosis. MATERIALS AND METHODS: A systematic review of the recent English-language literature was conducted according to the PRISMA statement recommendations (CRD42021250613) using PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases up to April 30, 2021. Risk-of-bias assessment was performed according to the QUADAS 2 tool. The true diagnostic value of urinary exosomes by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature. RESULTS: Sixteen eligible studies enrolling 3224 patients were identified. The pooled sensitivity and specificity of urinary exosomes as a diagnostic tool in urological tumors were 83% and 88%, respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89-0.94). Further subgroup analyses showed that our results were stable irrespective of the urinary exosome content type and tumor type. CONCLUSION: Urinary exosomes may serve as novel non-invasive biomarkers for urological cancer detection. Future clinical trial designs must validate and explore their utility in treatment decision-making. SYSTEMATIC REVIEW REGISTRATION: [ https://www.crd.york.ac.uk/prospero/], identifier [CRD42021250613].

Meta-Analysis of the Diagnostic Value of Cell-free DNA for Renal Cancer.

Cell-free DNA (cf-DNA) has been reported to represent a suitable material for liquid biopsy in the diagnosis and prognosis of various cancers. We performed a meta-analysis of published data to investigate the diagnostic value of cf-DNA for renal cancer (RCa). Systematic searches were conducted using Pubmed, Embase databases, Web of Science, Medline and Cochrane Library to identify relevant publications until the 31st March 2021. For all patients, we evaluated the true diagnostic value of cf-DNA by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature. In total, 8 studies, featuring 754 RCa patients, and 355 healthy controls, met our inclusion criteria. The overall diagnostic sensitivity and specificity for cf-DNA was 0.71 (95% confidence interval (CI), 0.55-0.83) and 0.79 (95% CI, 0.66-0.88), respectively. The pooled positive likelihood ratio and pooled negative likelihood ratio were 3.42 (95% CI, 2.04-5.72) and 0.36 (95% CI, 0.23-0.58), respectively. The area under the summary receiver operating characteristic curve was 0.82 (95% CI, 0.79-0.85), and the diagnostic odds ratio was 7.80 (95% CI, 4.40-13.85). Collectively, our data demonstrate that cf-DNA has high specificity and sensitivity for diagnosing RCa. Therefore, cf-DNA is a useful biomarker for the diagnosis of RCa.