A novel tumor cell origin-based risk score (TCOMRS) to predict liver metastasis and guide treatment in colon adenocarcinoma.
5 affiliations
- 1Department of Oncology, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- 2Department of Gastroenterology, Jiujiang University Affiliated Hospital, Jiujiang, China.
- 3Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
- 4Department of Integrated Traditional Chinese and Western Medicine Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.
- 5Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Abstract
Liver metastasis (LM) is a major determinant of poor prognosis in colon adenocarcinoma (COAD), yet reliable biomarkers for identifying patients at high metastatic risk remain limited. This study aimed to develop and validate a tumor cell origin-based metastasis risk score (TCOMRS) for characterizing LM-associated transcriptional features in COAD and to identify key molecular regulators involved in liver metastatic progression. Single-cell RNA sequencing (scRNA-seq) profiles from primary tumors and LM were integrated to identify distinct malignant-cell subpopulations and delineate their cellular origins. TCOMRS was constructed based on a one-class logistic regression (OCLR) algorithm trained with 4,512 malignant cells derived from LM, enabling assessment of the similarity between primary tumor cells and LM-associated malignant phenotypes. The clinical relevance of TCOMRS was validated across multiple independent cohorts, including The Cancer Genome Atlas (TCGA)-COAD, GSE39582, GSE38832, and GSE161158. Elevated TCOMRS was consistently associated with unfavorable overall survival, increased tumor stemness, and the presence of LM. Moreover, patients with low TCOMRS demonstrated improved responsiveness to immune checkpoint blockade therapy, suggesting potential utility in therapeutic decision-making. Mechanistically, fatty acid-binding protein 1 (FABP1) was identified as a key driver of LM, facilitating epithelial-mesenchymal transition and metastatic colonization. FABP1 expression correlated strongly with TCOMRS and metastatic propensity. Our findings establish TCOMRS as a robust biomarker for risk stratification and FABP1 as a promising therapeutic target, offering valuable insights for personalized treatment strategies in COAD.
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BibTeX
@article{gao2026novel,
title = {{A novel tumor cell origin-based risk score (TCOMRS) to predict liver metastasis and guide treatment in colon adenocarcinoma.}},
author = {Liping Gao and Lingxiu Zeng and Yabing Huo and Hao Liu and Jing Liu and Yong Li},
journal = {Translational cancer research},
year = {2026},
month = sep,
doi = {10.21037/tcr-2026-1049},
url = {https://europepmc.org/article/MED/42997878},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A novel tumor cell origin-based risk score (TCOMRS) to predict liver metastasis and guide treatment in colon adenocarcinoma.
AU - Liping Gao
AU - Lingxiu Zeng
AU - Yabing Huo
AU - Hao Liu
AU - Jing Liu
AU - Yong Li
PY - 2026
DA - 2026/09/28
JO - Translational cancer research
DO - 10.21037/tcr-2026-1049
UR - https://europepmc.org/article/MED/42997878
AB - Liver metastasis (LM) is a major determinant of poor prognosis in colon adenocarcinoma (COAD), yet reliable biomarkers for identifying patients at high metastatic risk remain limited. This study aimed to develop and validate a tumor cell origin-based metastasis risk score (TCOMRS) for characterizing LM-associated transcriptional features in COAD and to identify key molecular regulators involved in liver metastatic progression. Single-cell RNA sequencing (scRNA-seq) profiles from primary tumors and LM were integrated to identify distinct malignant-cell subpopulations and delineate their cellular origins. TCOMRS was constructed based on a one-class logistic regression (OCLR) algorithm trained with 4,512 malignant cells derived from LM, enabling assessment of the similarity between primary tumor cells and LM-associated malignant phenotypes. The clinical relevance of TCOMRS was validated across multiple independent cohorts, including The Cancer Genome Atlas (TCGA)-COAD, GSE39582, GSE38832, and GSE161158. Elevated TCOMRS was consistently associated with unfavorable overall survival, increased tumor stemness, and the presence of LM. Moreover, patients with low TCOMRS demonstrated improved responsiveness to immune checkpoint blockade therapy, suggesting potential utility in therapeutic decision-making. Mechanistically, fatty acid-binding protein 1 (FABP1) was identified as a key driver of LM, facilitating epithelial-mesenchymal transition and metastatic colonization. FABP1 expression correlated strongly with TCOMRS and metastatic propensity. Our findings establish TCOMRS as a robust biomarker for risk stratification and FABP1 as a promising therapeutic target, offering valuable insights for personalized treatment strategies in COAD.
SN - 2218-676X
SN - 2219-6803
ER -