Abstract
BACKGROUND: Colorectal cancer (CRC) is a highly aggressive, high-incidence malignancy. Several biomarkers associated with the prognosis and metastasis of CRC have been identified. Our study aimed to evaluate the value of ATG16L2 protein as a new biomarker to predict the prognosis of patients with CRC. METHODS: One hundred and fifty-two pairs of paraffin-embedded tissue samples and 19 fresh tissue samples were collected from the Department of Pathology of Renji Hospital, Shanghai Jiao Tong University School of Medicine. All the patients had undergone surgery in the hospital's Department of Gastrointestinal Surgery between 2013 and 2014. The samples were arranged on two tissue microarrays of normal (n=152) and tumor (n=152) tissue. The tissues were immunostained and graded as low (<50%) or high (≥50%) according to the proportion of ATG16L2-positive cells. An overexpression plasmid was constructed and transfected into RKO cells, and the cell proliferation and migration ability were detected. Finally, Flag-ATG16L2 RKO cells subcutaneous injection into the skin of BALB/c nude mice to determine the effects of ATG16L2 on the growth of subcutaneously transplanted tumors. RESULTS: ATG16L2 expression was negatively correlated with lymph node metastasis (P<0.05) and tumor-node-metastasis stage (P<0.05). High ATG16L2 expression in tumor tissues was related to a good prognosis, with patients with a high expression of ATG16L2 displaying longer overall survival. In vitro, overexpression of ATG16L2 in a CRC cell line RKO cell led to a decrease in cell proliferation but had no obvious influence on cell migration. In vivo, the mice in the Flag-NC (as control) group exhibited faster tumor growth than those in the experiment group. CONCLUSIONS: ATG16L2 expression is positively associated with patient prognosis in CRC. Further, ATG16L2 can negatively affect CRC cell proliferation in vitro and in vivo.