Keratin 6A (KRT6A) promotes radioresistance, invasion, and metastasis in lung cancer via p53 signaling pathway.

BACKGROUND: It is reported that the incidence rate and mortality of lung cancer are very high. Therefore, early diagnosis and identification of specific biomarkers are crucial for the clinical treatment of lung cancer. This study aims to comprehensively investigate the prognostic significance of KRT6A in human lung cancer. METHODS: The GEO2R online tool was utilized to analyze the differential expression of mRNA between lung carcinoma tissues and radioresistant tissues in the GSE73095 and GSE197236 datasets. DAVID database was used to perform GO and KEGG enrichment analyses on target genes. The Kaplan-Meier plotter tool was used to analyze the impact of key messenger ribonucleic acid on the survival status of lung cancer. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to investigate the impact of key genes on the phenotype of lung cancer cells. After the knockout, we conducted cell migration and CCK-8 experiments to detect their effects on cell proliferation and invasion. RESULTS: 40 differentially expressed genes (DEGs) were chosen from GSE73095 and 118 DEGs were chosen from GSE197236. Kaplan-Meier map analysis showed that the overall cancer survival rate of the high-expression KRT6A group was higher than that of the low-expression group (P < 0.05). Besides, cell experiments have shown that when the KRT6A gene is downregulated, the proliferation and invasion ability of lung cancer cells is weakened. CONCLUSIONS: Our research concluded that KRT6A may take part in the radioresistance and progression of lung cancer and can be a potential biomarker for lung cancer patients.

Causal Relationships of Chronic Constipation and Irritable Bowel Syndrome with Digestive Tract Cancers: A Mendelian Randomization Study.

BACKGROUND: Chronic constipation and irritable bowel syndrome (IBS) manifest as prevalent gastrointestinal disorders, while digestive tract cancers (DTCs) present formidable challenges to global well-being. However, extant observational studies proffer uncertain insights into potential causal relationships of constipation and IBS with susceptibility to DTCs. METHODS: We executed Mendelian randomization (MR) analysis to establish causal connections between these conditions and seven distinct categories of DTCs, including colorectal carcinoma (CRC), hepatocellular cancer (HCC), esophageal malignancy (ESCA), pancreatic adenocarcinoma (PAAD), biliary tract carcinoma (BTCs), gastric carcinoma (GC), and small intestine neoplasm (SIC). Leveraging instrumental variables (IVs) obtained from GWAS data of the FinnGen database, we employed a range of analytical methodologies, including inverse-variance weighting multiplicative random effects (IVW_MRE), inverse-variance weighting fixed effects (IVW_FE), maximum likelihood (ML), weighted median (WM), MR‒Egger regression, and the MR-PRESSO test. RESULTS: We observed a substantial linkage between genetically predicted constipation and increased vulnerability to PAAD (OR = 2.29, 95% CI: 1.422-3.69, P = 0.001) via the IVW method. Following the removal of outlier SNPs through MR-PRESSO, genetically predicted IBS was affiliated with an increased risk of CRC (OR = 1.17, 95% CI: 1-1.37, P = 0.05). Nonetheless, decisive causal correlations of constipation or IBS with other DTCs remain elusive. CONCLUSION: In summary, genetically predicted constipation was associated with an augmented PAAD risk, and IBS was associated with an increased CRC susceptibility within European cohorts, in agreement with some observational studies. Nevertheless, the causal associations of constipation and IBS with other DTCs remain inconclusive.

Identification of microRNA Signature and Key Genes Between Adenoma and Adenocarcinomas Using Bioinformatics Analysis.

BACKGROUND: In worldwide, colorectal cancer (CRC) is very common and the mechanisms remain unclear. This study aims to identify between adenomas with epithelial dislocation (false invasion) and adenomas with early adenocarcinoma (true invasion). METHODS: GSE41655 and GSE57965 datasets were obtained in the Gene Expression Omnibus (GEO) database. microRNA expression profiles and clinicopathological data from the TCGA (The Cancer Genome Atlas) database were downloaded to further validate the results in GEO. GEO software and the GEO2R calculation method were used to analyze two gene profiles. The co-expression of differentially expressed microRNAs (DEMs) and genes (DEGs) were identified and searched in the FunRich databases for pathway and ontology analysis. Cytoscape was utilized to construct the mRNA-microRNA network. Validation of gene expression levels was conducted by online databases and qRT-PCR and IHC experiments. RESULTS: In total, 6 DEMs and 34 DEGs are selected after calculating. KEGG results indicated that genes are enriched in certain tumor associated pathways. Four out of 6 microRNAs had a significant relationship with the overall survival (P < 0.05) and showed a good performance in predicting the survival risk of patients with colorectal carcinoma. Furthermore, expression levels of hsa-miR-455 and hsa-miR-125a were then verified by qRT-PCR which all target BCL2L12. IHC results showed that the expression level of BCL2L12 was higher in adenocarcinoma than in adenoma. Based on the selected gene, the top 10 small molecules were screened out as potential drugs. CONCLUSION: By using microarray and bioinformatics analyses, DEMs and DEGs were selected and a complete gene network was constructed. To our knowledge, BCL2L12 and related molecules including hsa-miR-455 and hsa-miR-125a were firstly identified as potential biomarkers in the progression from adenoma to adenocarcinoma.

HS3ST2 and Its Related Molecules as Potential Biomarkers for Predicting Lymph Node Metastasis in Patients with Colorectal Cancer.

BACKGROUND: Lymph node metastasis is a major cause of cancer-related death in patients with colorectal cancer (CRC), but current strategies are limited to predicting this clinical behavior. Our study aims to establish a lymph node metastasis prediction model based on miRNA and mRNA to improve the accuracy of prediction. METHODS: GSE56350, GSE70574, and GSE95109 were downloaded from the Gene Expression Omnibus (GEO) database and 569 colorectal cancer statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs were calculated by using R software. Besides, gene ontology and enriched pathway analysis of target mRNAs were analyzed by using FunRich. Furthermore, the mRNA-miRNA network was constructed using Cytoscape software. Gene expression level was also detected by performing qRT-PCR (quantitative real-time PCR) in colorectal cancer and lymph node tissues. RESULTS: In total, 5 differentially expressed miRNAs were selected, and 34 mRNAs were identified after filtering. The research of KEGG indicated that mRNAs are enriched in many cancer pathways. Differentially expressed miRNAs were most enriched in the cytoplasm, nucleoside, transcription factor activity, and RNA binding. KEGG pathway analysis of these target genes was mainly enriched in 5 pathways including fatty acid elongation, MAPK signaling pathway, autophagy, signaling pathways regulating pluripotency of stem cells, and Th17 cell differentiation. The results of qRT-PCR indicated that hsa-miR-100 and hsa-miR-99a were differentially expressed in lymph node metastatic colorectal cancer tissues and lymph node non-metastasis tissues which all target HS3ST2. Besides, we also found they have a significant difference in colorectal cancer tissues compared with normal tissues. CONCLUSION: By using microarray and bioinformatics analyses, differentially expressed miRNAs were identified and a complete gene network was constructed. To our knowledge, HS3ST2 and related molecules including hsa-miR-100 and hsa-miR-99a were firstly identified as potential biomarkers in the development of lymph node metastatic colorectal cancer.

Identification of Key miRNAs in the Treatment of Dabrafenib-Resistant Melanoma.

Dabrafenib resistance is a significant problem in melanoma, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism of drug resistance of dabrafenib and to explore the key genes and pathways that mediate drug resistance in melanoma. GSE117666 was downloaded from the Gene Expression Omnibus (GEO) database and 492 melanoma statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Besides, differentially expressed miRNAs (DEMs) were identified by taking advantage of the R software and GEO2R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and FunRich was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to identify potential pathways and functional annotations linked with melanoma chemoresistance. 9 DEMs and 872 mRNAs were selected after filtering. Then, target genes were uploaded to Metascape to construct protein-protein interaction (PPI) network. Also, 6 hub mRNAs were screened after performing the PPI network. Furthermore, a total of 4 out of 9 miRNAs had an obvious association with the survival rate (P < 0.05) and showed a good power of risk prediction model of over survival. The present research may provide a deeper understanding of regulatory genes of dabrafenib resistance in melanoma.

Identification of lymph node metastasis-related microRNAs in breast cancer using bioinformatics analysis.

BACKGROUND: Lymph node metastasis is a significant problem in breast cancer, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism and to explore the key RNAs and pathways that mediate lymph node metastasis in breast cancer. METHODS: GSE100453 and GSE38167 were downloaded from the Gene Expression Omnibus (GEO) database and 569 breast cancer statistics were also downloaded from the TCGA database. Differentially expressed miRNAs were calculated by using R software and GEO2R. Gene ontology and Enriched pathway analysis of target mRNAs were analyzed by using the Database for Database of Annotation Visualization and Integrated Discovery (DAVID) and R software. The protein-protein interaction (PPI) network was performed according to Metascape, String, and Cytoscape software. RESULTS: In total, 6 differentially expressed miRNAs were selected, and 499 mRNAs were identified after filtering. The research of the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that mRNAs enriched in certain tumor pathways. Also, certain hub mRNAs were highlighted after constructed and analyzed the PPI network. A total of 3 out of 6 miRNAs had a significant relationship with the overall survival (P < .05) and showed a good ability of risk prediction model of over survival. CONCLUSIONS: By utilizing bioinformatics analyses, differently expressed miRNAs were identified and constructed a complete gene network. Several potential mechanisms and therapeutic and prognostic targets of lymph node metastasis were also demonstrated in breast cancer.

The prognostic and clinicopathological significance of RBM3 in the survival of patients with tumor: A Prisma-compliant meta-analysis.

BACKGROUND: RNA-binding motif protein 3 (RBM3) plays an important role in carcinogenesis and tumor progression. However, the prognostic role of RBM3 in human carcinomas remains controversial. Therefore, we took a meta-analysis to research the association between the overall survival of patients with cancer and the expression of RBM3. METHODS: Systematic literature research identified 17 potentially eligible studies comprising 4976 patients in ten different cancer types. Two researchers independently screened the content and quality of studies and extracted data. Correlations of RBM3 expression and survival were analyzed and the hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: In the pooled analysis, overexpression of RBM3 was related to improved overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS) in patients with cancer having a pooled HR of 0.61 (HR = 0.61; 95% CI: 0.47-0.69), 0.57 (HR = 0.60; 95% CI: 0.50-0.71) and 0.54 (HR 0.54; 95% CI: 0.38-0.78). Besides, subgroup analysis proved that overexpression of RBM3 was related to improved OS in colorectal cancer (HR = 0.61, 95% CI: 0.43-0.86), melanoma (HR = 0.32, 95% CI: 0.20-0.52), and gastric cancer (HR = 0.51, 95% CI: 0.35-0.73). However, subgroup analysis according to tumor type revealed that overexpression of RBM3 was not related to better OS in breast carcinoma (HR = 0.52, 95% CI: 0.17-0.61). CONCLUSIONS: Our results indicated that RBM3 overexpression was significantly predictive of better prognosis in various human cancers. For certain tumors, overexpression RBM3 might be a marker of improved survival in humans with cancer, except for breast cancer.

Comparison between ultrasound-guided TIVAD via the right innominate vein and the right internal jugular vein approach.

BACKGROUND: To compare the efficacy and safety of right internal jugular vein (IJV) approach and right innominate vein (INV) approach for US-guided totally implantable venous access devices (TIVADs), and to explore the advantages and disadvantages of the two approaches. METHODS: Six hundred and nineteen adult patients had long-term infusion and chemotherapy needs and inconvenience of peripheral venous infusion. Right INV approach was used to implant 339 cases of TIVADs, and right IJV approach was used to implant 280 cases of TIVADs. The success rate of one-time catheterization and the incidence of complications in the two groups were retrospectively analyzed. RESULTS: All patients were successfully implanted in TIVAD. The success rates of one-time puncture in INV group and IJV approach group were 98.53% (334/339) and 95.36% (267/280), respectively. There was significant difference between the two groups (P = 0.020). The incidence of perioperative complications and long-term complications in the right INV group were 1.18% (4/339) and 3.54% (12/339), respectively, while those in the right IJV group were 1.43% (4280) and 3.93% (11280). There was no significant difference in the incidence of perioperative or long-term complications between the two groups (P = 0.785, P = 0.799, respectively). CONCLUSIONS: US-guided TIVADs via the right INV approach and the right IJV approach are both safe and reliable. The right INV approach improves the one-time puncture success rate, as long as the technique is properly operated, serious complications rarely occur.

Prognostic significance of CIP2A expression in solid tumors: A meta-analysis.

CIP2A, cancerous inhibitor of protein phosphatase 2A, was initially recognized as an oncoprotein. Recently several studies revealed that CIP2A could function as a prognosis biomarker, however, the result remained not comprehensive, partly due to small number of patients included individually. Here we carried out a meta-analysis of published studies to assess the prognostic significance of CIP2A in solid tumors. All eligible studies were identified through searching PubMed, Embase and Web of Science database. In this meta-analysis, 22 studies involving 4,579 participants were included, and we verified that CIP2A over-expression was significantly related with poor overall survival (pooled HR = 1.844, 95% CI = 1.528-2.225, P<0.001) and short disease free survival (pooled HR = 1.808, 95% CI = 1.591-2.055, P<0.001) in solid tumors. Additionally, subgroup analysis suggested that the trend of a poor overall survival with an increased CIP2A expression was present in East-Asian and European patients, as well as in lung cancer and colorectal cancer. To sum up, CIP2A over-expression was associated with poor survival in human solid tumors and might be a predictive factor of poor prognosis.