High Level of ASXL1 Protein Is Associated With Better Disease-Free Survival in Colorectal Cancer

Abstract

Background: ASXL1 gene is on chromosome region 20q11.21. Either amplification in cervical cancer or truncation mutations in colorectal cancers with microsatellite instability (MSI), malignant myeloid diseases, chronic lymphocytic leukemia, liver, prostate and breast cancers occurred. The functional and the prognostic roles of ASXL1 mutations and the expression of protein in colorectal cancer are still unknown. Aim: The aim of this study is to investigate the functional roles of ASXL1 mutations and the expression of protein in colorectal cancer. Methods: We performed NGS of 10 colorectal cancer with peritoneal seeding to find genetic markers for aggressive phenotype. All showed a frameshift deletion at codon 1934delG. To clinically validate the functional and the prognostic roles of the mutations, we performed an immunohistochemical staining (IHC) on tissue microarrays of 414 consecutive colorectal cancers. Results: The ASXL1 protein expression was strong positive in 5.8% (24 patients), moderate positive in 38.5% (157 patients) and negative in 55.6% (227 patients). The patients with negative ASXL1 expression had more lymph node metastasis than the patients with strong positive expression [59.0% (134/227 patients) vs 33.3% (8/24 patients), P = 0.038]. None of the patients with strong positive expression had recurrent disease in the stage I-III cancers [0% (0/21 patients) vs 19.4% (27/139 patients) vs 18.9% (34/180 patients)] and the disease-free survival rate of the patients with strong positive expression was significantly better than that of the patients with moderate positive or negative expression ( P = 0.037; P = 0.031). Conclusion: The decreased level of the expression of the ASXL1 protein was associated with lymph node metastasis in its progression of cancer. Strong positive ASXL1 protein expression was a 'good' prognostic factor of colorectal cancers. The ASXL1 protein might be tumor suppressive in colorectal cancer.