Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer

Abstract

Colorectal cancer is one of the malignant tumors with the highest mortality rate in the world. Survival rates vary significantly among patients at various stages of the disease. A biomarker capable of early diagnosis is required to facilitate the early detection and treatment of colorectal cancer. Human endogenous retroviruses (HERVs) are abnormally expressed in various diseases, including cancer, and have been involved in cancer development. Real-time quantitative PCR was used to detect the transcript levels of HERV-K(HML-2) gag, pol, and env in colorectal cancer to systematically investigate the connection between HERV-K(HML-2) and colorectal cancer. The results showed that HERV-K(HML-2) transcript expression was significantly higher than healthy controls and was consistent at the population and cell levels. We also used next-generation sequencing to identify and characterize HERV-K(HML-2) loci that were differentially expressed between colorectal cancer patients and healthy individuals. The analysis revealed that these loci were concentrated in immune response signaling pathways, implying that HERV-K impacts the tumor-associated immune response. Our results indicated that HERV-K might serve as a screening tumor marker and a target for tumor immunotherapy in colorectal cancer.

Human Endogenous Retrovirus-K (HML-2)-Related Genetic Variation: Human Genome Diversity and Disease

“…Consequently, such insertion polymorphism can affect phenotypic diversity and potentially influence the susceptibility of an individual to specific diseases [3]. In addition, SNP variants in HERV-K (HML-2) can affect the activity and function of host genes [94]. In particular, depending on where the SNP occurs, it can affect the structure and function of proteins in various ways, including altering the binding sites of transcription factors and microRNAs [95].…”

“…Additionally, these regions are present in the human genome either in heterozygous or homozygous states, indicating that they are not yet fixed [3,31]. Currently, these HERV-K (HML-2) loci are being reported to have associations in various cancer and disease studies [3,62,94,[97][98][99]. The diverse forms of variations, namely SNP, duplication, deletion, and insertion polymorphism, influence the activity, expression, and functional alterations of HERV-K (HML-2), ultimately impacting the host physiologically [3].…”

Exploring HERV-K (HML-2) Influence in Cancer and Prospects for Therapeutic Interventions

“…HERV envs could serve as targets for both passive and active immunotherapies against cancer. In certain cancers, such as melanoma and colorectal carcinoma, HERV-K (HML-2) envs have been investigated as tumor-associated antigens (TAAs) and tumor-specific antigens (TSAgs) for stimulating immune responses against cancer cells [147][148][149][150]. Moreover, combining HERV-based immunotherapy with demethylating agents has been proposed to enhance anticancer effects.…”