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Colon Cancer Combined with Obesity Indicates Improved Survival - Research on Relevant Mechanism
32 Pages Posted: 8 Jul 2020
More...Abstract
Background: Obesity contributes to the incidence of various tumors, including colon cancer. However, the impact of obesity on patients’ survival and related mechanisms remain unclear.
Methods: Multi-omics research data of 227 cases colon cancer patients combined with clinical characteristics data were acquired from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier method and Cox regression model were used for analysis the relationship of obesity and Overall Survival (OS). Transcriptome data were normalized to gene expression data through the R software package “Limma”. Somatic mutations data were analyzed and visualized through the R software package “maftools”. CIBERSORT algorithm was used to estimate the relative proportion of 22 infiltrating immune cell types.
Findings: We confirmed obesity as an independent prognostic factor for improved Overall Survival (OS) of colon cancer patients. We demonstrated that hypoxia pathways were repressed in obesity patients through regulating miR-210. Immune checkpoints PD-1 and LAG3 were also downregulated in obesity patients, which indicated enhanced immune surveillance. Meanwhile, gama delta T cells (γδT) was decreased in obesity patients, who reduced expression of IFN-γ. The frequency of PIK3CA and KRAS mutations was decreased in obesity patients. The sites and types of TP53 mutation were alternated in obesity patients.
Interpretation: Our research demonstrated the potential mechanisms of prolonged survival in colon cancer patients combined with obesity and may provide potential value for improving prognosis of colon cancer through obesity-linked mechanisms.
Funding Statement: The present study was funded by Outstanding Clinical Discipline Project of Shanghai Pudong and Program for Medical Key Departments of Shanghai.
Declaration of Interests: The authors declare no potential conflicts of interest.
Ethics Approval Statement: All procedures involving human participants were performed in accordance with Shanghai Pudong Hospital ethical committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All patients provided their written informed consent. The study protocol was approved by the Pudong Hospital Committee on human research.
Keywords: Obesity, Colon cancer, Hypoxia, Immune checkpoints, TP53
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