Charting the metabolic biogeography of the colorectum in cancer - challenging the right sided versus left sided classification

Sep 21, 2026

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Objective: Colorectal cancer (CRC) is conventionally divided into right-sided, left-sided, and rectal cancer, yet clinicopathological, molecular features, and risk factors change gradually along the colorectum and even vary within refined subsites. Design: Using 372 patient-matched tumor and normal mucosa samples, liquid chromatography-mass spectrometry mapped metabolomic profiles across seven colorectal subsites. Results: Metabolite abundances showed inter-subsitemetabolic heterogeneity and linear concentration gradients, with subsite-specific survival-associated metabolites. Conclusions: The findings support reevaluating CRC subsite classification and provide an interactive CRC metabolome database for biomarker discovery.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Jain et al. Molecular Cancer (2024) 23:211 Molecular Cancer [https://doi.org/10.1186/s12943-024-02133-5](https://doi.org/10.1186/s12943-024-02133-5) CORRESPONDENCE Open Access Charting the metabolic biogeography of the colorectum in cancer: challenging the right sided versus left sided classification Abhishek Jain 1, Montana T. Morris2, Domenica Berardi 1, Trisha Arora3, Xavier Domingo-Almenara3, Philip B. Paty4, Nicholas J. W. Rattray5, Daniel Kerekes2, Lingeng Lu6, Sajid A. Khan2* and Caroline H. Johnson 1* Abstract Objective Colorectal cancer (CRC) is conventionally classified as right sided, left sided, and rectal cancer. Clinicopathological, molecular features and risk factors do not change abruptly along the colorectum, and variations exist even within the refined subsites, which may contribute to inconsistencies in the identification of clinically relevant CRC biomarkers. We generated a CRC metabolome map to describe the association between metabolites, diagnostic and survival heterogeneity in cancers of different subsites of the colorectum. Design Utilizing 372 patient-matched tumor and normal mucosa tissues, liquid chromatography-mass spectrometry was applied to examine metabolomic profiles along seven subsites of the colorectum: cecum (n = 63), ascending colon (n = 44), transverse colon (n = 32), descending colon (n = 28), sigmoid colon (n = 75), rectosigmoid colon (n = 38), and rectum (n = 92) . Results 39 and 70 significantly altered metabolites (including bile acids, lysophosphatidylcholines and lysophosphatidylethanolamines) among tumors and normal mucosa, respectively, showed inter-subsite metabolic heterogeneity between CRC subsites. Gradual changes in metabolite abundances with significantly linear trends from cecum to rectum were observed: 23 tumor-specific metabolites, 30 normal mucosa-specific metabolites, and 15 metabolites in both tumor and normal mucosa, had concentration gradients across the colorectum, and is disease status dependent. The metabolites that showed a linear trend included bile acids, amino acids, lysophosphatidylcholines, and lysophosphatidylethanolamines. Comparison of tumors to patient-matched normal mucosa revealed metabolite changes exclusive to each subsite, thereby further highlighting differences in cancer metabolism across the 7 subsites of the colorectum. Furthermore, metabolites associated with survival were different and unique to each subsite. Finally, an interactive and publicly accessible CRC metabolome database was designed to enable access and utilization of this rich data resource ( [https://colorectal-cancer-metabolome.com/yale-university](https://colorectal-cancer-metabolome.com/yale-university)) . Conclusions Gradual changes exist in metabolite abundances from the cecum to the rectum. The association between patient survival and distinct metabolites with anatomic subsite of the colorectum, reveals differences *Correspondence: Sajid A. Khan[sajid.khan@yale.edu](sajid.khan@yale.edu)[ ](sajid.khan@yale.edu)Caroline H. Johnson [caroline.johnson@yale.edu](caroline.johnson@yale.edu) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended u

FAQs

What problem does the study address in colorectal cancer classification?

It addresses that CRC does not change abruptly from right-sided to left-sided to rectal cancer, and that refined subsite differences may cause inconsistency in identifying clinically relevant CRC biomarkers.

How was the metabolome map for CRC generated?

Researchers used 372 patient-matched tumor and normal mucosa tissues and applied liquid chromatography-mass spectrometry to profile metabolites across seven colorectal subsites.

What major metabolomic patterns were observed across the colorectum?

The study found inter-subsitemetabolic heterogeneity and gradual linear changes in metabolite abundances from the cecum to the rectum, including bile acids, amino acids, lysophosphatidylcholines, and lysophosphatidylethanolamines.

Sep 21, 2026

Upload by Miles