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Exp. Mol. Med., 07 January 2026 | https://doi.org/10.1038/s12276-025-01599-7 Colorectal microenvironment determines the prognosis of colorectal cancer

Yeong Hak Bang ^1,2,20, Ji Hye Choi ^1,3,20, Kyunghee Park ¹, Boram Lee ⁴, Kyung Yeon Han ¹, Dae Hee Pyo ^5,6, Yong Beom Cho ⁵, Tae-You Kim ^7,8,9,10, Kyu Joo Park ¹¹, Seung-Bum Ryoo ¹¹, Sung-Bum Kang ¹², Chang Sik Yu ¹³, Jaeim Lee¹⁴, Kil yong Lee ¹⁴, Kyu-Tae Kim ¹⁵, Jin-Young Lee ¹⁶, Hoang Bao Khanh Chu ¹⁶, Nameeta Shah ^1,17, Shashank Gupta ¹⁷, Pranali Sonpatki ¹⁷, Young-Joon Kim ^16,18 and Woong-Yang Park ^1,3,19,*

¹Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea.
²Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Republic of Korea.
³Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
⁴Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
⁵Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
⁶Department of Colorectal and Anal Surgery, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University, Seoul, Republic of Korea.
⁷Division of Hematooncology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁸Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁹IMBdx Inc., Seoul, Republic of Korea.
¹⁰Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
¹¹Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
¹²Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
¹³Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
¹⁴Department of Surgery, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University, Uijeongbu, Republic of Korea.
¹⁵Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.
¹⁶Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
¹⁷Amaranth Medical Analytics, Bengaluru, India.
¹⁸LepiDyne Co. Ltd., Seoul, Republic of Korea.
¹⁹Geninus, Seoul, Republic of Korea.
²⁰These authors contributed equally: Yeong Hak Bang, Ji Hye Choi.

^*Corresponding author: correspondence to Woong-Yang Park

Abstract

Here we aimed to evaluate the feasibility of distinguishing colorectal microenvironments that support cancer cell growth from those that do not. We hypothesized that patients whose non-tumor-bearing tissue (NBT) obtained from the furthest margins of resected cancer specimens resembled the tumor had a poorer prognosis. Patients with colorectal cancer were divided into groups with tumor-supportive (TSM) or healthy microenvironments using bulk RNA sequencing data from 273 paired NBT and tumor samples. Patients in the TSM group exhibited significantly poorer 5-year recurrence-free survival and overall survival compared with those in the healthy microenvironment group. Pathway and 16S rRNA sequencing analyses revealed that NBT and tumors from the TSM group shared a microbiome composition, along with decreased pathway activity related to microvilli maintenance and flavonoid or vitamin metabolic processes. Single-cell RNA sequencing uncovered upregulated interactions between IL1B^high neutrophils and OLFM4⁺ epithelial cells in NBTs from the TSM group, as well as organized microniches in TSM tumors, featuring interactions between EMP1^high epithelial cells, IL1B^high neutrophils and GZMK^high CD8⁺ T cells. Collectively, the colorectal microenvironment can serve as a prognostic biomarker to effectively predict cancer invasiveness and tumor-promoting inflammation. Maintaining a healthy colorectal mucosal microenvironment, potentially through dietary intervention, is crucial.

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