TCGA database analysis of the tumor mutation burden and its clinical significance in colon cancer

Chen, Junjie; Apizi, Anwaier; Wang, Lin; Wu, Guanting; Zhu, Zheng; Yao, Heng‐Chen; Chen, Guoliang; Shi, Xinyu; Shi, Bo; Tai, Qingliang; Shen, Cunsi; Wu, Lingzhi; He, Songbing

doi:10.21037/jgo-21-661

Cited by 7 publications

(4 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In KEGG pathway analyses, these common DEGs were found to be enriched in the Neuroactive ligandreceptor interaction,cell adhesion molecules and protein digestion and absorption pathways. There's a strong possibility that the Neuroactive ligand-receptor interaction pathway is a key regulator of metastatic progression and chemoresistance in colorectal cancer [49].The neuroactive ligand receptor interaction pathway may be participated in the regulation of tumor mutational burden(TMB) characterized by microsatellite instability. Since TMB has become a impactful predictor of tumor transformation and immunotherapeutic response, the regulatory pathway of neuroactive ligand receptor interaction may exert an meaningful effection.…”

Section: Discussionmentioning

confidence: 99%

A novel N7-methylguanosine(m7G) methylation-associated miRNA signature for prognostic value in patient with carcinoma of colon

Wang¹,

Liu²

2022

Preprint

View full text Add to dashboard Cite

Background:m7G methylation-associated genes were selected as the main research perspectives in this study, establishing a novel m7G methylation-associated miRNA risk signature for prognostic value in patient with carcinoma of colon. Methods:We identified two genes that are m7G methylation-associated and have been validated by searching in the PubMed database.The m7G methylation-associated miRNAs were screened via estimating the differentially expressed of miRNAs in 457 carcinoma of colon patient samples and 8 matched samples from a database named The Cancer Genome Atlas (TCGA). SelectingSingle-factor Cox analyses as well as multi-factor Cox analyses constructed the risk signature of 12 m7G methylation-associated miRNAs.Nomograms was adopted to predict the potential impact of m7G methylation-associated miRNAs on occurrence, development.The functions of DEGs that deserving to be noticed were classified and analyzed by functional enrichment analysis.Disease ontology analysis was used to explore the potential connection various diseases and carcinoma of colon.The outcome of associated analysis about immunocyte or immunological functioning revealed that what role does immunocyte or immunological functioning play in the development of carcinoma of colon.Finally, the relationship between high or low expression of significantly DEGs and immune cells and immune function was analyzed. Results:The results of nomogram analysis were as follows that the risk signature might predict the prognosis and the overall cumulative probability of survival（1-,3-,5-year） effectively about patients with carcinoma of colon. Through the analysis of Kaplan-Meier curve outcomes, we can draw a conclusion that depressedly expressed of hsa-miR-21-3p might be significantly relevant with decreased survival of patients.What the analyses of Gene ontology (GO) , Kyoto Encyclopedia of Genes and Genomes (KEGG) and Disease ontology（DO）,taking advantage of the common DEGs about risk score and immune score,demonstrated that these common DEGs play a partial role in the occurrence and development of tumors.Through disease ontology analysis,we found that eating disorder might be associated with carcinoma of colon. Conclusions: m7G methylation-associated miRNAs were related to the prognosis of patients with carcinoma of colon. A risk signature established based on these miRNAs could effectively predict the survival rate of later period in patients with carcinoma of colon.According to the displayed outcom from Our research that m7G methylation-associated miRNA regulators can serve as reliable prognostic biomarkers of carcinoma of colon, which might Greater probably be applyed as potential targets of therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel N7-methylguanosine(m7G) methylation-associated miRNA signature for prognostic value in patient with carcinoma of colon

Wang¹,

Liu²

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In KEGG pathway analyses, these common DEGs were found to be enriched in the Neuroactive ligand-receptor interaction, cell adhesion molecules and protein digestion and absorption pathways. There is a strong possibility that the Neuroactive ligand-receptor interaction pathway is a key regulator of metastatic progression and chemo resistance in colorectal cancer [49].…”

Section: Discussionmentioning

confidence: 99%

A Novel N7-Methylguanosine (M7g) Methylation-Associated Mirna Signature for Prognostic Value in Patient with Carcinoma of Colon

2022

JGEBR

View full text Add to dashboard Cite

Background M7G methylation-associated genes were selected as the main research perspectives in this study, establishing a novel m7G methylation-associated miRNA risk signature for prognostic value in-patient with carcinoma of colon. Methods We identified two genes that are m7G methylation-associated and have been validated by searching in the PubMed database. The m7G methylation-associated miRNAs were screened via estimating the differentially expressed of miRNAs in 457 carcinoma of colon patient samples and 8 matched samples from a database named The Cancer Genome Atlas (TCGA). Selecting Single-factor Cox analyses as well as multi-factor Cox analyses constructed the risk signature of 12 m7G methylation-associated miRNAs. Nomograms was adopted to predict the potential impact of m7G methylation-associated miRNAs on occurrence, development. The functions of DEGs that deserving to be noticed were classified and analyzed by functional enrichment analysis. Disease ontology analysis was used to explore the potential connection various diseases and carcinoma of colon. The outcome of associated analysis about immunocyte or immunological functioning revealed that what role does immunocyte or immunological functioning play in the development of carcinoma of colon. Finally, the relationship between high or low expression of significantly DEGs and immune cells and immune function was analyzed. Results The results of nomogram analysis were as follows that the risk signature might predict the prognosis and the overall cumulative probability of survival (1-,3-,5-year) effectively about patients with carcinoma of colon. Through the analysis of Kaplan-Meier curve outcomes, we can draw a conclusion that depressed expressed of hsa-miR-21-3p might be significantly relevant with decreased survival of patients. What the analyses of Gene ontology (GO) , Kyoto Encyclopedia of Genes and Genomes (KEGG) and Disease ontology(DO),taking advantage of the common DEGs about risk score and immune score, demonstrated that these common DEGs play a partial role in the occurrence and development of tumors. Through disease ontology analysis, we found that eating disorder might be associated with carcinoma of colon. Conclusions M7G methylation-associated miRNAs were related to the prognosis of patients with carcinoma of colon. A risk signature established based on these miRNAs could effectively predict the survival rate of later period in patients with carcinoma of colon .According to the displayed outcome from Our research that m7G methylation-associated miRNA regulators can serve as reliable prognostic biomarkers of carcinoma of colon, which might Greater probably be applied as potential targets of therapeutic strategies.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Gene mutation is frequently observed in tumor development and is one of the most common reasons for tumor aggressiveness and poor prognosis ( Chen et al, 2021 ), which is also known as tumor mutation burden (TMB). High TMB tumors are usually correlated with the deficiency of DNA repair, microsatellite instability, and a high possibility of drug resistance though they may attract more immune cell infiltration ( Chen et al, 2021 ; Xiao et al, 2021 ). K-Ras gene is one of the most popular and well-defined oncogene that mutates in a broad range of solid tumors ( Der et al, 1982 ), including lung adenocarcinoma (∼30%) ( Siegfried et al, 1997 ), pancreatic adenocarcinoma (∼70%–90%) ( Visani et al, 2013 ), stomach cancer (∼10%) ( Lee et al, 2003 ), and colorectal cancer (∼30%–50%) ( Andreyev et al, 1998 ; Downward, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of colon cancer K-RasG13D mutation reduces cancer cell proliferation but promotes stemness and inflammation via RAS/ERK pathway

Yan

Zou²,

Zhao³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

K-Ras is a well-studied oncogene, and its mutation is frequently found in epithelial cancers like pancreas, lung, and colorectal cancers. Cancer cells harboring K-Ras mutations are difficult to treat due to the drug resistance and metastasis properties. Cancer stem cells (CSCs) are believed the major cause of chemotherapeutic resistance and responsible for tumor recurrence and metastasis. But how K-Ras mutation affects CSCs and inflammation is not clear. Here, we compared two colon cancer cell lines, HCT-116 and HT-29, with the former being K-RasG13D mutant and the latter being wildtype. We found that HCT-116 cells treated with a K-Ras mutation inhibitor S7333 formed significantly more tumor spheroids than the untreated control, while the wild type of HT-29 cells remained unchanged. However, the size of tumor spheroids was smaller than the untreated controls, indicating their proliferation was suppressed after S7333 treatment. Consistent with this, the expressions of stem genes Lgr5 and CD133 significantly increased and the expression of self-renewal gene TGF-β1 also increased. The flow cytometry analysis indicated that the expression of stem surface marker CD133 increased in the treated HCT-116 cells. To understand the pathway through which the G13D mutation induced the effects, we studied both RAS/ERK and PI3K/Akt pathways using specific inhibitors SCH772984 and BEZ235. The results indicated that RAS/ERK rather than PI3K/Akt pathway was involved. As CSCs play the initial role in cancer development and the inflammation is a vital step during tumor initiation, we analyzed the correlation between increased stemness and inflammation. We found a close correlation of increased Lgr5 and CD133 with proinflammatory factors like IL-17, IL-22, and IL-23. Together, our findings suggest that K-RasG13D mutation promotes cancer cell growth but decreases cancer stemness and inflammation thus tumorigenesis and metastasis potential in colon cancer. Inhibition of this mutation reverses the process. Therefore, care needs be taken when employing targeted therapies to K-RasG13D mutations in clinics.

show abstract

TCGA database analysis of the tumor mutation burden and its clinical significance in colon cancer

Cited by 7 publications

References 52 publications

A novel N7-methylguanosine(m7G) methylation-associated miRNA signature for prognostic value in patient with carcinoma of colon

A novel N7-methylguanosine(m7G) methylation-associated miRNA signature for prognostic value in patient with carcinoma of colon

A Novel N7-Methylguanosine (M7g) Methylation-Associated Mirna Signature for Prognostic Value in Patient with Carcinoma of Colon

Inhibition of colon cancer K-RasG13D mutation reduces cancer cell proliferation but promotes stemness and inflammation via RAS/ERK pathway

Contact Info

Product

Resources

About