A distance-related model identified PDCD6IP as a local host protective factor in colorectal cancer

Tumor-host interactions play an important role in cancer initiation and progression. To investigate changes in local host factors associated with proximity to the tumor, the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients were used to establish a distance-related model. Two distance-related expression patterns were considered, one with a trend toward gradual down-regulation and one with a trend toward gradual up-regulation as the distance from the tumor decreased. Gene Ontology (GO) analysis highlighted 7 genes enriched in the endosomal sorting complex required for transport (ESCRT) machinery in the group with a pattern of gradual down-regulation. Survival analysis of patients in the TCGA colorectal cancer (CRC) dataset revealed that higher expression of two of these genes (PDCD6IP and CHMP2B) was associated with a better prognosis (p = 0.021, p = 0.031). A tissue array confirmed that patients with up-regulated PDCD6IP expression in cancer tissue compared with normal tissue had better prognoses (p = 0.04). In conclusion, we built a distance-related model to study the local tumor-host interactions and identified PDCD6IP as a local host protective factor in CRC. The samples were collected from 32 rectal cancer patients who underwent surgical resection at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences from 2014 to 2015. We collected rectal cancer tissue samples (T) and histologically normal tissue samples located at varying distances from the tumors, including 1 cm away from the tumor (N1), 5 cm away from the tumor (N5) and as far as possible away from the tumor (N15).