Identification of shared genetic features and molecular mechanisms of metabolic syndrome and colorectal cancer based on transcriptomic data

Deng Jielian; Li Kangjie; Zhang Cong; Zhang Yuan; Xie Biao; Zhong Xiaoni; Zheng Wei

doi:10.13406/j.cnki.cyxb.003389

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Identification of shared genetic features and molecular mechanisms of metabolic syndrome and colorectal cancer based on transcriptomic data

Bioinformatics analysis | 更新时间：2025-10-22

- Identification of shared genetic features and molecular mechanisms of metabolic syndrome and colorectal cancer based on transcriptomic data
- Journal of Chongqing Medical University Vol. 48, Issue 12, Pages: 1514-1519(2023)
- 作者机构：
  
  1.重庆医科大学公共卫生学院流行病与卫生统计教研室,重庆 401331
  2.重庆医科大学附属第一医院心内科,重庆　400016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003389
  CLC： R735.3
- Received：28 September 2023，
  
  Revised：2023-11-05，
  
  Accepted：19 November 2023，
  
  Published：28 December 2023
- 稿件说明：
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邓洁莲,李康杰,张聪,等.基于转录组数据识别代谢综合征与结直肠癌的共同基因特征和分子机制[J].重庆医科大学学报,2023,48(12):1514-1519.

Deng Jielian,Li Kangjie,Zhang Cong,et al.Identification of shared genetic features and molecular mechanisms of metabolic syndrome and colorectal cancer based on transcriptomic data[J].Journal of Chongqing Medical University,2023,48(12):1514-1519.
邓洁莲,李康杰,张聪,等.基于转录组数据识别代谢综合征与结直肠癌的共同基因特征和分子机制[J].重庆医科大学学报,2023,48(12):1514-1519. DOI： 10.13406/j.cnki.cyxb.003389.

Deng Jielian,Li Kangjie,Zhang Cong,et al.Identification of shared genetic features and molecular mechanisms of metabolic syndrome and colorectal cancer based on transcriptomic data[J].Journal of Chongqing Medical University,2023,48(12):1514-1519. DOI： 10.13406/j.cnki.cyxb.003389.

摘要

目的

识别代谢综合征（metabolic syndrome，MetS）与结直肠癌（colorectal cancer，CRC）共同的基因特征和生物学通路，并筛选与MetS相关的CRC预后生物标志物。

方法

对MetS、CRC和相应的对照样本进行差异分析，以识别表达差异的基因作为与疾病相关的基因。根据这些基因的表达特征进行功能富集分析，以识别受调控的生物学功能。利用单因素Cox回归鉴定与CRC预后相关的MetS基因，并使用LASSO和多因素Cox回归分析构建CRC的预后预测模型。基于汇总数据的孟德尔随机化分析（Summary-data-based Mendelian Randomization，SMR）进一步确认MetS基因与CRC预后的因果关系。

结果

325个基因在MetS和CRC中表达上调，281个基因表达下调。研究还发现，Apelin信号和胞吐等通路在2种疾病中被抑制，而核酸修复通路则被激活。其中，有60个与MetS和CRC共享的基因与CRC的预后相关。18个基因被用于构建预测模型，在TCGA数据库的CRC队列中，模型在1~5年的曲线下面积（area under the curve，AUC）值均大于0.75，表现出良好的预测性能。通过SMR分析进一步确定，P4HA1和LARS2与CRC预后具有因果关系。

结论

MetS和CRC具有共同的基因特征和通路，炎症可能为2种疾病相关的基础，共享基因对CRC的预后有影响。

Abstract

Objective

To identify shared genetic features and biological pathways between metabolic syndrome（MetS） and colorectal cancer（CRC），and to screen for prognostic biomarkers associated with MetS in CRC.

Methods

First，differential analysis was performed on MetS，CRC，and their corresponding control samples to identify genes with differential expression，which were used as disease-related genes. Subsequently，functional enrichment analysis was performed based on the expression characteristics of these genes to identify the regulated biological functions. Then，single-factor Cox regression was used to identify MetS genes associated with CRC prognosis，and LASSO and multivariate Cox regression analysis were used to construct a model for prediction of CRC prognosis. Finally，the causal relationship between MetS genes and CRC prognosis was further confirmed through Summary-data-based Mendelian Randomization.

Results

A total of 325 genes were upregulated and 281 genes were downregulated in both MetS and CRC. Apelin signaling and endocytosis pathways were inhibited and the nucleotide excision repair pathway was activated in both diseases. Among them，60 genes shared between MetS and CRC were associated with CRC prognosis. Eighteen genes were employed to construct a prediction model. In the CRC cohort of the TCGA database，the model demonstrated robust prediction performance with the area under the curve exceeding 0.75 for the 1-5 year period. Summary-data-based Mendelian Randomization analysis confirmed the causal relationship of P4HA1 and LARS2 with CRC prognosis.

Conclusion

MetS and CRC share genetic features and pathways，with inflammation as a possible link between these two diseases. Shared genes can influence the prognosis of CRC.

关键词

Keywords

references

Song MY ， Bretthauer M . Interpreting epidemiologic studies of colonoscopy screening for colorectal cancer prevention：understanding the mechanisms of action is key [J ] . Eur J Epidemiol ， 2023 ， 38 （ 9 ）： 929 - 931 ．

Sung H ， Ferlay J ， Siegel RL ， et al . Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin ， 2021 ， 71 （ 3 ）： 209 - 249 ．

Norris P ， Gow J ， Arthur T ， et al . Metabolic syndrome and surgical complications：a systematic review and meta-analysis of 13 million individuals [J ] . Int J Surg ， 2023 ： 201 - 213 ．

Zhang CC ， Zhang LT ， Tian Y ， et al . Association between metabolic syndrome and early-stage colorectal cancer [J ] . BMC Cancer ， 2023 ， 23 （ 1 ）： 1020 ．

Han F ， Wu GH ， Zhang S ， et al . The association of metabolic syndrome and its components with the incidence and survival of colorectal cancer：a systematic review and meta-analysis [J ] . Int J Biol Sci ， 2021 ， 17 （ 2 ）： 487 - 497 ．

Rahman MR ， Islam T ， Shahjaman M ， et al . Discovering common pathogenetic processes between COVID-19 and diabetes mellitus by differential gene expression pattern analysis [J ] . Brief Bioinform ， 2021 ， 22 （ 6 ）： bbab262 ．

Gallon J ， Coto-Llerena M ， Ercan CE ， et al . Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma [J ] . Mol Oncol ， 2022 ， 16 （ 3 ）： 665 - 682 ．

Ritchie ME ， Phipson B ， Wu D ， et al . Limma powers differential expression analyses for RNA-sequencing and microarray studies [J ] . Nucleic Acids Res ， 2015 ， 43 （ 7 ）： e47 ．

Wu TZ ， Hu EQ ， Xu SB ， et al . clusterProfiler 4.0：a universal enrichment tool for interpreting omics data [J ] . Innovation （Camb）， 2021 ， 2 （ 3 ）： 100141 ．

Langfelder P ， Horvath S . WGCNA：an R package for weighted correlation network analysis [J ] . BMC Bioinformatics ， 2008 ， 9 ： 559 ．

Zhu ZH ， Zhang FT ， Hu H ， et al . Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets [J ] . Nat Genet ， 2016 ， 48 （ 5 ）： 481 - 487 ．

Sawane M ， Kidoya H ， Muramatsu F ， et al . Apelin attenuates UVB-induced edema and inflammation by promoting vessel function [J ] . Am J Pathol ， 2011 ， 179 （ 6 ）： 2691 - 2697 ．

Weimershaus M ， Carvalho C ， Rignault R ， et al . Mast cell-mediated inflammation relies on insulin-regulated aminopeptidase controlling cytokine export from the Golgi [J ] . J Allergy Clin Immunol ， 2023 ， 151 （ 6 ）： 1595 - 1608 ．

Šebeková K ， Staruchová M ， Mišľanová C ， et al . Association of inflammatory and oxidative status markers with metabolic syndrome and its components in 40-to-45-year-old females：a cross-sectional study [J ] . Antioxidants ， 2023 ， 12 （ 6 ）： 1221 ．

Greten FR ， Grivennikov SI . Inflammation and cancer：triggers，mechanisms，and consequences [J ] . Immunity ， 2019 ， 51 （ 1 ）： 27 - 41 ．

Milanese C ， Bombardieri CR ， Sepe S ， et al . DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering [J ] . Nat Commun ， 2019 ， 10 （ 1 ）： 4887 ．

Liu Y ， Gu YJ ， Ng S ， et al . Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression [J ] . Sci Bull ， 2020 ， 65 （ 18 ）： 1570 - 1579 ．

Li ZJ ， Bao HY . Comparative transcriptome and proteome analysis explores the antitumor key regulators of ergosterone in H22 tumor-bearing mice [J ] . Eur J Pharmacol ， 2023 ， 953 ： 175831 ．

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