Objective Prostate cancer (PCa) is a malignant neoplasm of the urinary system. This study aimed to use bioinformatics to screen for core genes and biological pathways related to PCa. Methods The GSE5957 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were constructed by R language. Furthermore, protein–protein interaction (PPI) networks were generated to predict core genes. The expression levels of core genes were examined in the Tumor Immune Estimation Resource (TIMER) and Oncomine databases. The cBioPortal tool was used to study the co-expression and prognostic factors of the core genes. Finally, the core genes of signaling pathways were determined using gene set enrichment analysis (GSEA). Results Overall, 874 DEGs were identified. Hierarchical clustering analysis revealed that these 24 core genes have significant association with carcinogenesis and development . LONRF1, CDK1, RPS18, GNB2L1 ( RACK1), RPL30, and SEC61A1 directly related to the recurrence and prognosis of PCa. Conclusions This study identified the core genes and pathways in PCa and provides candidate targets for diagnosis, prognosis, and treatment.
Background Long non-coding RNAs (lncRNAs) have become potential therapeutic targets or promising prognostic biomarkers in cancers. However, individual gene does not show sufficient prognostic value for clear cell renal cell carcinoma (ccRCC). Therefore, this study aims to develop a combined prognostic lncRNA signature to the prognosis of ccRCC. Methods The transcriptome profiling data for confirmed ccRCC cases were obtained from The Cancer Genome Atlas (TCGA; https://portal.gdc.cancer.gov/ ). The prognostic significance, survival time and diagnostic effectiveness of the lncRNAs in ccRCC was evaluated using Kaplan-Meier method, the log-rank test and receiver operating characteristic (ROC) curves, respectively. The area under the ROC curve (AUC) of the 4 lncRNAs was also performed. The expression of mitotically-associated lncRNA (MANCR) was measured in ccRCC cells or tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Both Colony formation assays and Cell Counting Kit-8 (CCK-8) assay was conducted to detect the proliferation of both 786-O and SN12C cells. For apoptosis detection, flow cytometry in both 786-O and SN12C cells was performed. For migration of 786-O and SN12C cells detection, wound healing and transwell assays were performed. Results A total of 1,567 differentially expressed lncRNAs in ccRCC were discerned with 1,340 upregulation and 227 downregulation. Furthermore, a 4-lncRNA signature ( FIRRE , MANCR , AC103706.1 , and AC018648.1 ) model was obtained that showed good performance in the prognosis of ccRCC. Gene Ontology (GO) analysis showed that these protein-coding genes (PCGs) were mainly enriched in ATPase activity, catalytic activity, and acting on RNA protein serine/threonine kinase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that PCGs were mainly involved in endocytosis, oocyte meiosis and spliceosome. In addition, we revealed that MANCR was highly expressed in ccRCC cells and tissues and downregulation of MANCR inhibited cell proliferation and migration. In contrast, apoptosis of 786-O and SN12C cells was promoted with MANCR suppression. Conclusions A 4-lncRNA prognostic model that presented good performance for prognosis of ccRCC patients was established. Knockdown of MANCR inhibited cell proliferation and migration, and promoted apoptosis of 786-O and SN12C cells, suggesting that a 4-lncRNA signature model might be an essential for ccRCC prognosis.
Background miR-92a is believed to have a significant role in the diagnosis and prognosis of different types of tumors, but the potential impact of its expression is still controversial due to the sample size. We conducted the meta-analysis to figure out whether miR-92a could be used as a detecting tool for assessing the prognosis of gastric cancer. Method A literature search was conducted by retrieving the Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure, VIP (Technology of Chongqing databases), and Wanfang databases (last updated by February 2020). The sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the ROC curve (AUC) were pooled to explore the diagnostic performance of miR-92a. The pooled hazard ratios (HRs) and 95% CIs of miR-92a for overall survival (OS) were calculated to explore the prognostic performance of miR-92a. Results Nine articles containing 11 studies were included. The pooled SEN and SPE were 0.76 and 0.79. Besides, the pooled PLR and NLR were 3.7 and 0.30, and the pooled DOR was 12. AUC was 0.84, indicating a significant value of miR-92a in gastric cancer detection. For the prognostic analysis of miR-92a in gastric cancer, the univariate and multivariate data’s poor OS were 1.37 and 2.01. Conclusion The present meta-analysis demonstrated that miR-92a could be a potential biomarker for the detection of gastric cancer. miR-92a could also be used as a valuable indicator for predicting the prognosis of gastric cancer patients.
BackgroundUpper tract urothelial carcinoma (UTUC) is a rare malignancy. The management of metastatic or unresectable UTUC is mainly based on evidence extrapolated from histologically homologous bladder cancer, including platinum-based chemotherapy and immune checkpoint inhibitor alone, whereas UTUC exhibits more invasiveness, worse prognosis, and comparatively inferior response to treatments. First-line immunochemotherapy regimens have been attempted in clinical trials for unselected naïve-treated cases, but their efficacies relative to standard chemo- or immuno-monotherapy still remain controversial. Here, we present a case of highly aggressive UTUC for whom comprehensive genetic and phenotypic signatures predicted sustained complete response to first-line immunochemotherapy.Case presentationA 50-year-old man received retroperitoneoscopic nephroureterectomy and regional lymphadenectomy for high-risk locally advanced UTUC. Postoperatively, he developed rapid progression of residual unresectable metastatic lymph nodes. Pathologic analysis and next-generation sequencing classified the tumor as highly aggressive TP53/MDM2-mutated subtype with features more than expression of programmed death ligand-1, including ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state. Immunochemotherapy combining gemcitabine, carboplatin, and off-label programmed death-1 inhibitor sintilimab was initiated, and sintilimab monotherapy was maintained up to 1 year. Retroperitoneal lymphatic metastases gradually regressed to complete response. Blood-based analyses were performed longitudinally for serum tumor markers, inflammatory parameters, peripheral immune cells, and circulating tumor DNA (ctDNA) profiling. The ctDNA kinetics of tumor mutation burden and mean variant allele frequency accurately predicted postoperative progression and sustained response to the following immunochemotherapy, which were mirrored by dynamic changes in abundances of ctDNA mutations from UTUC-typical variant genes. The patient remained free of recurrence or metastasis as of this publishing, over 2 years after the initial surgical treatment.ConclusionImmunochemotherapy may be a promising first-line option for advanced or metastatic UTUC selected with specific genomic or phenotypic signatures, and blood-based analyses incorporating ctDNA profiling provide precise longitudinal monitoring.
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