학술논문
HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
Document Type
article
Author
Mahdi Golkaram; Michael L. Salmans; Shannon Kaplan; Raakhee Vijayaraghavan; Marta Martins; Nafeesa Khan; Cassandra Garbutt; Aaron Wise; Joyee Yao; Sandra Casimiro; Catarina Abreu; Daniela Macedo; Ana Lúcia Costa; Cecília Alvim; André Mansinho; Pedro Filipe; Pedro Marques da Costa; Afonso Fernandes; Paula Borralho; Cristina Ferreira; Fernando Aldeia; João Malaquias; Jim Godsey; Alex So; Traci Pawlowski; Luis Costa; Shile Zhang; Li Liu
Source
npj Genomic Medicine, Vol 6, Iss 1, Pp 1-11 (2021)
Subject
Language
English
ISSN
2056-7944
Abstract
Abstract Colorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P