Two Transcriptomic Analyses Converge on a Five-Gene Core for Colorectal Cancer Discrimination: External Validation in Independent Tissue Cohorts.
7 affiliations
- 1División de Medicina Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico.
- 2Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
- 3División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico.
- 4Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
- 5Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico.
- 6Coordinador Auxiliar Médico de Investigación en Salud, Coordinación de Planeación y Enlace Institucional, OOAD Jalisco, Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico.
- 7Coordinador Clínico de Educación e Investigación en Salud, OOAD Jalisco, Instituto Mexicano del Seguro Social (IMSS) Guadalajara 44340, Jalisco, Mexico.
Abstract
Background/Objectives: Colorectal cancer (CRC) is a leading cause of neoplasia-related morbidity and mortality worldwide and the first cause of cancer death in Mexico, where early detection remains a challenge, and reliable molecular biomarkers could support earlier diagnosis. Transcriptomic signatures for CRC have been published, but different studies arrive at gene lists that barely overlap, and since each study differs in both cohort and analysis, the source of that disagreement cannot be identified. This study aimed to identify a gene set for CRC discrimination whose selection depends neither on how the batch effect is handled nor on the criterion by which candidates are chosen and to validate that set in repositories that took no part in its selection. Methods: The signature was identified in 104 public RNA-seq samples (79 tumor, 25 reference) obtained from six BioProjects of the NCBI Sequence Read Archive and analyzed twice. A functionally anchored route took one representative gene per enriched biological program, ranked by π-value, from a differential expression model including BioProject as a covariate; a regularization route selected genes by their stability under Elastic Net in nested cross-validation over a ComBat-Seq-adjusted matrix. The genes reached by both routes were corroborated in TCGA-COAD, TCGA-READ, and GTEx colon processed by recount3 (n = 1542), with every parameter held fixed, and in the GEO microarray series GSE37364 (the 65 carcinoma and normal-mucosa samples of a 94-sample series), where only the coefficient vector was transferred because the platform differs; they were further examined descriptively in a second adenoma series (GSE89076), published stool RNA-seq, and plasma cell-free RNA. Results: The two routes yielded a seven-gene and a five-gene signature sharing a single gene, RPGRIP1L. Five genes met both criteria: TRIP13, CEMIP, PUS7, RPGRIP1L, and SLC22A3. With every parameter held fixed, the five-gene core reached an AUC of 0.9993 in TCGA/GTEx (sensitivity 0.966, specificity 0.998); with its coefficients transferred and the intercept recalibrated, it reached 0.9737 in GSE37364 (sensitivity 0.926, specificity 0.974). All five were elevated in adenoma relative to normal mucosa in GSE37364, and three of the five reached significance in GSE89076, where only five adenomas were available; all five were overexpressed in published stool RNA-seq of CRC patients. Conclusions: A five-gene core, TRIP13, CEMIP, PUS7, RPGRIP1L, and SLC22A3, discriminates colorectal tumor tissue from non-tumor in repositories external to its selection, with elevation already present in premalignant adenoma. Having been reached by two routes that share neither criterion nor starting point, these five genes are candidates for experimental validation and for evaluation in material accessible without biopsy.
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BibTeX
@article{tovarjacome2026transcriptomic,
title = {{Two Transcriptomic Analyses Converge on a Five-Gene Core for Colorectal Cancer Discrimination: External Validation in Independent Tissue Cohorts.}},
author = {César de Jesús Tovar-Jácome and Luis Felipe Jave-Suárez and Jesús García-Gómez and Adriana Aguilar-Lemarroy and Augusto Sarralde-Delgado and Juan Manuel Carranza-Rosales and Jaime Patricio Barros-Núñez and Mónica Alejandra Rosales-Reynoso},
journal = {Genes},
year = {2026},
month = sep,
doi = {10.3390/genes17101177},
url = {https://europepmc.org/article/MED/42938293},
note = {CC BY},
}
RIS
TY - JOUR
TI - Two Transcriptomic Analyses Converge on a Five-Gene Core for Colorectal Cancer Discrimination: External Validation in Independent Tissue Cohorts.
AU - César de Jesús Tovar-Jácome
AU - Luis Felipe Jave-Suárez
AU - Jesús García-Gómez
AU - Adriana Aguilar-Lemarroy
AU - Augusto Sarralde-Delgado
AU - Juan Manuel Carranza-Rosales
AU - Jaime Patricio Barros-Núñez
AU - Mónica Alejandra Rosales-Reynoso
PY - 2026
DA - 2026/09/24
JO - Genes
DO - 10.3390/genes17101177
UR - https://europepmc.org/article/MED/42938293
AB - Background/Objectives: Colorectal cancer (CRC) is a leading cause of neoplasia-related morbidity and mortality worldwide and the first cause of cancer death in Mexico, where early detection remains a challenge, and reliable molecular biomarkers could support earlier diagnosis. Transcriptomic signatures for CRC have been published, but different studies arrive at gene lists that barely overlap, and since each study differs in both cohort and analysis, the source of that disagreement cannot be identified. This study aimed to identify a gene set for CRC discrimination whose selection depends neither on how the batch effect is handled nor on the criterion by which candidates are chosen and to validate that set in repositories that took no part in its selection. Methods: The signature was identified in 104 public RNA-seq samples (79 tumor, 25 reference) obtained from six BioProjects of the NCBI Sequence Read Archive and analyzed twice. A functionally anchored route took one representative gene per enriched biological program, ranked by π-value, from a differential expression model including BioProject as a covariate; a regularization route selected genes by their stability under Elastic Net in nested cross-validation over a ComBat-Seq-adjusted matrix. The genes reached by both routes were corroborated in TCGA-COAD, TCGA-READ, and GTEx colon processed by recount3 (n = 1542), with every parameter held fixed, and in the GEO microarray series GSE37364 (the 65 carcinoma and normal-mucosa samples of a 94-sample series), where only the coefficient vector was transferred because the platform differs; they were further examined descriptively in a second adenoma series (GSE89076), published stool RNA-seq, and plasma cell-free RNA. Results: The two routes yielded a seven-gene and a five-gene signature sharing a single gene, RPGRIP1L. Five genes met both criteria: TRIP13, CEMIP, PUS7, RPGRIP1L, and SLC22A3. With every parameter held fixed, the five-gene core reached an AUC of 0.9993 in TCGA/GTEx (sensitivity 0.966, specificity 0.998); with its coefficients transferred and the intercept recalibrated, it reached 0.9737 in GSE37364 (sensitivity 0.926, specificity 0.974). All five were elevated in adenoma relative to normal mucosa in GSE37364, and three of the five reached significance in GSE89076, where only five adenomas were available; all five were overexpressed in published stool RNA-seq of CRC patients. Conclusions: A five-gene core, TRIP13, CEMIP, PUS7, RPGRIP1L, and SLC22A3, discriminates colorectal tumor tissue from non-tumor in repositories external to its selection, with elevation already present in premalignant adenoma. Having been reached by two routes that share neither criterion nor starting point, these five genes are candidates for experimental validation and for evaluation in material accessible without biopsy.
SN - 2073-4425
ER -