Expression of Human Endogenous Retrovirus Env Gene Product Is a Hallmark of Sidedness in Operable Colorectal Cancer

Introduction: Human endogenous retroviruses (HERVs) account for approximately 8% of the human genome, where they are integrated and typically remain silent. Despite their inactivation, numerous retroviral sequences retain intact open reading frames capable of producing retroviral transcripts and/or proteins, which have been detected in colon cancer. Methods: Three different cohorts of patients who underwent surgery at three different hospitals, comprising 167 Italian and Tunisian colon cancer patients, were analyzed. The expression levels of HERV-H, -K, -P env genes and HERV-K pol gene were assessed in tumor and adjacent healthy tissues using quantitative polymerase chain reaction. Correlative analysis was conducted to investigate associations between clinicopathological factors, including tumor location, stage, patient age, lymphocyte infiltration, and vascular/perineural invasion, and HERV gene expression levels. Results: HERV gene expression level was similar among samples from tumor and from adjacent healthy tissues. Significant (p < 0.05) higher expression of HERV-P and -R env was observed in tumor tissues arising from right colon than from left colon, while HERV-H env was more (p < 0.05) expressed in the left colon than in the right colon. A significant increase in the expression of HERV-H and -K env, following the increasing severity of tumor grade, was observed in the tumor tissue. HERV-H and -P env genes were more expressed in patients under 73 and over 73 years old, respectively, in the tumor tissue. Conclusion: In colorectal cancer, HERV env gene expression seems to represent a specific signature in tumor and/or adjacent healthy tissues, based on tumor location and patients' age. Analyzing differential HERV expression and its correlation with clinicopathological patient characteristics could be valuable for identifying novel biomarkers and exploring potential therapeutic targets in colon cancer.