Immune and Stromal Related Genes in Colon Cancer: Analysis of Tumor Microenvironment Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) Databases

Author(s):  
Yue Wu ◽  
Haowei Jia ◽  
Hangyuan Zhou ◽  
Xinyu Liu ◽  
Junfeng Sun ◽  
...  
2018 ◽  
Vol 33 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Min-hang Zhou ◽  
Hong-wei Zhou ◽  
Mo Liu ◽  
Jun-zhong Sun

Purpose: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. Methods: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan–Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. Results: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.


2021 ◽  
Vol 15 (1) ◽  
pp. 29-41
Author(s):  
Peng Qiao ◽  
Di Zhang ◽  
Song Zeng ◽  
Yicun Wang ◽  
Biao Wang ◽  
...  

Aim: This study aims to identify novel marker to predict biochemical recurrence (BCR) in prostate cancer patients after radical prostatectomy with negative surgical margin. Materials & methods: The Cancer Genome Atlas database, Gene Expression Omnibus database and Cancer Cell Line Encyclopedia database were employed. The ensemble support vector machine-recursive feature elimination method was performed to select crucial gene for BCR. Results: We identified MYLK as a novel and independent biomarker for BCR in The Cancer Genome Atlas training cohort and confirmed in four independent Gene Expression Omnibus validation cohorts. Multi-omic analysis suggested that MYLK was a DNA methylation-driven gene. Additionally, MYLK had significant positive correlations with immune infiltrations. Conclusion: MYLK was identified and validated as a novel, robust and independent biomarker for BCR in prostate cancer.


2017 ◽  
pp. 1-12
Author(s):  
Manish R. Sharma ◽  
James T. Auman ◽  
Nirali M. Patel ◽  
Juneko E. Grilley-Olson ◽  
Xiaobei Zhao ◽  
...  

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.


2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Wei Han ◽  
Biao Huang ◽  
Xiao-Yu Zhao ◽  
Guo-Liang Shen

Abstract Skin cutaneous melanoma (SKCM) is one of the most deadly malignancies. Although immunotherapies showed the potential to improve the prognosis for metastatic melanoma patients, only a small group of patients can benefit from it. Therefore, it is urgent to investigate the tumor microenvironment in melanoma as well as to identify efficient biomarkers in the diagnosis and treatments of SKCM patients. A comprehensive analysis was performed based on metastatic melanoma samples from the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm, including gene expression, immune and stromal scores, prognostic immune-related genes, infiltrating immune cells analysis and immune subtype identification. Then, the differentially expressed genes (DEGs) were obtained based on the immune and stromal scores, and a list of prognostic immune-related genes was identified. Functional analysis and the protein–protein interaction network revealed that these genes enriched in multiple immune-related biological processes. Furthermore, prognostic genes were verified in the Gene Expression Omnibus (GEO) databases and used to predict immune infiltrating cells component. Our study revealed seven immune subtypes with different risk values and identified T cells as the most abundant cells in the immune microenvironment and closely associated with prognostic outcomes. In conclusion, the present study thoroughly analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for metastatic melanoma.


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