Immune Signaling Gene ZAP70 Shows Reduced Activity in Colorectal Polyps

Colorectal polyps, the small growths that can precede colorectal cancer, appear to carry measurable molecular differences long before malignancy develops. A new exploratory study published in BMC Immunology reports that two molecules, the immune signaling gene ZAP70 and the long non-coding RNA lnc-FAHD2B-3, are significantly downregulated in polyp tissue compared with the healthy mucosa immediately adjacent to it. A third molecule examined in the same samples, the long non-coding RNA TRERNA1, showed no significant difference in expression at all.

The research team, led by Parasto Atri and Flora Forouzesh with colleagues including Claudia Cava, analyzed matched colorectal polyp and adjacent mucosal samples from 31 patients undergoing colonoscopy. Using reverse-transcription quantitative PCR, a sensitive laboratory technique that amplifies and quantifies specific RNA sequences, the researchers measured the expression levels of ZAP70, TRERNA1, and lnc-FAHD2B-3 in each paired tissue sample.

It has previously been found dysregulated in several malignancies, which is why the authors selected it for investigation in early colorectal neoplasia. TRERNA1 and lnc-FAHD2B-3 had been linked to cancer biology in prior work, but their involvement in colorectal polyps specifically remained largely unexplored before this study.

The finding that both ZAP70 and lnc-FAHD2B-3 were downregulated in polyps, while TRERNA1 was unchanged, suggests a selective molecular signature rather than a broad shutdown of these transcripts. However, the researchers also report that no significant correlation was detected between ZAP70 and either long non-coding RNA, meaning the coordinated behavior of these molecules in polyp tissue could not be demonstrated in this cohort.

To place their measurements in a wider context, the team turned to publicly available Gene Expression Omnibus datasets, a large repository of gene expression data. Their in silico analyses of these colorectal cancer datasets indicated that higher ZAP70 expression was associated with more favorable relapse-free survival. This is an association observed in retrospective dataset analysis, not a causal demonstration, and it concerns established colorectal cancer rather than the polyp stage examined in the qPCR experiments.

The study also tested whether expression levels differed between independently defined high- and low-risk groups of patients. No statistically significant expression differences were observed between these groups, so the measured molecular changes could not be tied to a clinical risk classification within this sample.

The authors are explicit about the limits of their work. In the study’s conclusions, they state that the small cohort and the exploratory design preclude clinical or mechanistic conclusions, and that the findings require validation in larger, independent cohorts.

What the study does establish is a concrete, testable observation: in this cohort, polyp tissue expressed less ZAP70 and less lnc-FAHD2B-3 than the matched adjacent mucosa, a pattern consistent with the idea that immune-related signaling and non-coding RNA regulation are altered at the earliest stages of colorectal neoplasia. Because colorectal cancer often develops from precursor lesions such as adenomatous polyps, identifying which molecular changes occur at this precancerous stage is a recognized priority in the field, and the authors note that the molecular alterations associated with early colorectal neoplasia remain incompletely understood.

For now, the appropriate reading of this study is cautious. It is an open-access, peer-reviewed exploratory molecular analysis, currently shared as an accepted manuscript that may undergo further edits before the final version of record. Its value lies in generating specific hypotheses, for example whether reduced ZAP70 expression in polyps relates to the local immune environment, or whether lnc-FAHD2B-3 downregulation marks a particular pathway of early tumor development. Confirming or refuting those hypotheses will require the larger, independent validation cohorts the authors themselves call for, and any clinical implications will have to wait for that evidence.

Subject of Research: Expression of the immune signaling gene ZAP70 and long non-coding RNAs in colorectal polyps

Article Title: Altered expression of ZAP70 and lnc-FAHD2B-3 in colorectal polyps: an exploratory molecular study

Article References: Atri, P., Forouzesh, F., Nazemalhosseini-Mojarad, E., Mirbahari, S. N., & Cava, C. (2026). Altered expression of ZAP70 and lnc-FAHD2B-3 in colorectal polyps: an exploratory molecular study. BMC Immunology. https://doi.org/10.1186/s12865-026-00905-w

Image Credits: AI Generated

DOI: 10.1186/s12865-026-00905-w

Keywords: colorectal polyps, ZAP70, lnc-FAHD2B-3, TRERNA1, long non-coding RNA, RT-qPCR, colorectal cancer, gene expression, early neoplasia, BMC Immunology, exploratory study, relapse-free survival