RESUMO
BACKGROUND: Mitochondrial RNA polymerase (POLRMT) is essential for the expression of mitochondrial genes. In recent studies, POLRMT expression promoted non-small cell cancer cell proliferation in cell lines and xenografts. The present study investigated the impact of POLRMT expression and function on lung adenocarcinoma (LUAD) patients. METHOD: Multi-omics data (genomics, transcriptomics, and proteomics) from publicly available databases were used to assess the role of POLRMT expression and function in LUAD. These findings were further verified using cancer tissues from clinical samples. RESULTS: POLRMT was over-expressed in LUADs, with mutation frequencies ranging from 1.30% to 5.71%. Over-expression of POLRMT was associated with an abnormal clinicopathological condition resulting in a decreased lifespan. Furthermore, gene sets enrich analysis revealed that POLRMT expression was linked to WNT/beta-catenin signaling; the expression of downstream target genes was positively correlated with POLRMT expression. Also, POLRMT expression was positively correlated with immunosuppressive genes, thereby affecting immune infiltration. CONCLUSION: POLRMT is over-expressed in LUAD, thereby impacting patient survival. It is also involved in WNT/beta-catenin signaling and may affect tumor infiltration.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/patologia , Via de Sinalização Wnt/genética , RNA Polimerases Dirigidas por DNA/metabolismoRESUMO
Background: Colorectal cancer (CRC), one of the main causes of death, remains a leading cause of mortality in gastrointestinal cancer and tends to affect the younger generation. However, the pathological process of colorectal cancer is unclear. Exploring potential pathogenesis and therapeutic targets of CRC is significant as its high prevalence and high mortality. Nowadays, the rapid development of bioinformatics provides us an opportunity to explore potential molecular markers of CRC. Materials and Methods: First, three CRC gene chips with paracancerous controls were downloaded from the Gene Expression Omnibus (GEO) database. Second, after combining and batch correcting the three chips using the R language and Perl language, the differentially expressed genes (DEGs) were selected to investigate how they affect the CRC occurrence and development by GO and KEGG enrichment analysis. Third, based on the STRING website and the Cytoscape software, the protein-protein interaction (PPI) network was constructed and the core genes were screened out. Finally, through polymerase chain reaction (PCR) and immunohistochemistry (IHC), the expression and function of the core gene CXCL8 in CRC were explored. Results: GSE10950, GSE44076, and GSE75970, including 126 intestinal cancer samples and 126 paracancer samples, were screened as the datasets. 192 DEGs were screened, including 43 upregulated genes and 149 downregulated genes. Through the DEGs screened out, GO enrichment analysis, KEGG enrichment analysis, and the construction of PPI interaction network were carried out. Finally, according to the nodes and edges in the PPI network, the DEGs were sorted and the core genes were selected. Through basic experiments, the first ranked CXCL8 was further studied, and the results suggest that the expression of CXCL8 is related to the proliferation, migration, invasion, and even distant metastasis of CRC. Conclusion: The present study showed that DEGs of CRC are associated with multiple tumor-related biological processes and signaling pathways. The core gene CXCL8 has the potential to be a new therapeutic target for CRC.
Assuntos
Neoplasias Colorretais , Biologia Computacional , Neoplasias Colorretais/patologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Humanos , Prognóstico , Mapas de Interação de Proteínas/genéticaRESUMO
Background: Serine hydroxymethyltransferase (SHMT) is critical for one-carbon unit metabolism and is increasingly reported to be associated with tumor patients' outcomes. Thus, we designed and performed this meta-analysis to reveal its prognostic role and relationship with clinicopathological characteristics in human cancer. Methods: A systematic search of PubMed, Embase, Web of Science and Cochrane Library (CENTRAL) was carried out. Two reviewers independently screened all references for eligibility according to the inclusion criteria. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality and data was extracted for the meta-analysis. Results: Ten studies, composed of 1,942 patients in total, were included in this meta-analysis. Higher expression of SHMT2 means an unfavorable prognosis [overall survival: hazard ratio (HR) =2.14, 95% confidence interval (CI): 1.53 to 2.99; progression-free survival (PFS)/disease-free survival (DFS)/recurrence-free survival (RFS): HR =1.90, 95% CI: 1.31 to 2.76]. Furthermore, higher SHMT2 expression is associated with larger tumor size [odds ratio (OR) =2.09, 95% CI: 1.58 to 2.77], more lymph node invasions [OR =2.67, 95% CI: 1.78 to 4.00), and higher tumor node metastasis classification (TNM) stage (OR =2.23, 95% CI: 1.55 to 3.21). Higher expression of SHMT2 is also related to higher histopathological grade (OR =3.46, 95% CI: 1.46 to 8.27) and distant metastasis (OR =1.25, 95% CI: 0.32 to 4.90), however, with significant heterogeneity (I2=61%, P=0.08 for distant metastasis; I2=82%, P<0.001 for histopathological grade). The prognostic clinical role of SHMT1 in clinical patients has not been directly investigated yet. Discussion: SHMT2 may serve as a promising prognostic biomarker in various cancer, especially in the alimentary system. Further large-scale studies are warranted to verify the possible effect.