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Copyright ©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Feb 24, 2026; 17(2): 113428
Published online Feb 24, 2026. doi: 10.5306/wjco.v17.i2.113428
Gene and cytokine expression profiles of metastatic colorectal cancer patients post reovirus administration
Vivian Zweig, Sanjay Goel, Radhashree Maitra
Vivian Zweig, Department of Biology, Washington University, Saint Louis, MO 63130, United States
Sanjay Goel, Division of Medical Oncology, RJW Barnabas Health, Rutgers Cancer Institute, New Brunswick, NJ 08901, United States
Radhashree Maitra, Department of Biology, Yeshiva University, New York, NY 10033, United States
Author contributions: Zweig V performed all the pathway analysis and comparison with the cytokine expression; Maitra R conceptualized and performed the RNA sequencing; Goel S evaluated the analysis, drafting, and revising of the article; and all authors thoroughly reviewed and endorsed the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Albert Einstein College of Medicine, No. 10-02-037.
Informed consent statement: All patient blood samples were drawn with informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The authors have shared individual deidentified participant data in the public domain to be available indefinitely. These raw data include peripheral mononuclear cell samples at four timepoints (pre-treatment, 48 hours, day 8 and day 15) for each individual involved in the clinical trial. This data can be accessed through the NCBI GEO Accession Viewer (Series GSE173636) using the following URL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173636.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Radhashree Maitra, Full Professor, Department of Biology, Yeshiva University, 500 W 185th Street, New York, NY 10033, United States. radhashree.maitra@yu.edu
Received: August 28, 2025
Revised: October 14, 2025
Accepted: January 4, 2026
Published online: February 24, 2026
Processing time: 165 Days and 4 Hours
Abstract
BACKGROUND

Colorectal cancer (CRC), encompassing both colon and rectal carcinogenesis, is a major health concern. Metastatic CRC (mCRC) is the third most common cancer and the second leading cause of cancer-related death in United States adults. Despite advances in therapy, the 5-year survival rate remains low at 15%. KRAS mutations contribute to treatment resistance by altering the tumor microenvironment, necessitating novel therapeutic approaches.

AIM

To evaluate immunomodulatory and cytotoxic potential of reovirus as an adjuvant therapy in KRAS-mutant-mCRC patients by analyzing gene and cytokine expression.

METHODS

Five KRAS-mutant mCRC patients were treated with reovirus. Serum samples were collected at five time points over 15 days. Cytokine levels were measured using enzyme-linked immunosorbent assay, and transcriptomic profiling was performed to assess gene expression. Data were analyzed using the 2-ΔΔCt method, and statistical significance was determined via two-tailed t-tests (P < 0.05).

RESULTS

Out of 271 genes associated with Janus kinase/signal transducer and activator of transcription, Ras, Wnt, and phosphoinositide 3-kinase- alpha serine/threonine-protein kinase pathways, 85 showed significant modulation. Additionally, 17 of 25 cytokines were significantly altered. Reovirus induced changes in both gene and cytokine expression, suggesting activation of a complex intracellular signaling network.

CONCLUSION

Reovirus demonstrates potential as an immunomodulatory and cytotoxic adjuvant in KRAS-mutant mCRC by altering key signaling pathways and cytokine profiles. These findings support further investigation into its potential therapeutic contributions.

Keywords: Metastatic colorectal cancer; Oncolytic reovirus; KRAS; Cytokine signaling; Janus kinase/signal transducer and activator of transcription; Phosphoinositide 3-kinase-alpha serine/threonine-protein kinase

Core Tip: This study highlights the prospective of reovirus as both an immunomodulatory agent and a cytotoxic adjuvant to chemotherapy in patients with KRAS-mutant metastatic colorectal cancer. Reovirus induces anti-tumor immunity by modulating cytokine expression - reducing interleukin-8 and vascular endothelial growth factor to inhibit angiogenesis, while elevating interleukin-6, interferon-gamma and regulated upon activation, normal T-cell expressed and secreted to stimulate inflammation. These findings support further investigation into reovirus’s role in reshaping the immune landscape and enhancing therapeutic outcomes in metastatic colorectal cancer.