Decreased expression of MS4A12 inhibits differentiation and predicts early stage survival in colon cancer

Lack of normal differentiation was considered as a common defect in cancer cells. MS4A12, a colon-specific gene, belongs to MS4A family that plays an important role in differentiation, proliferation and cell cycle regulation. The aim of the study was to investigate MS4A12 role in colon cancer cell differentiation and its prognostic value in colon cancer. We used sodium butyrate (BS) to set up differentiated model of colon cancer cell line LoVo. Cell differentiation was evaluated with ALP activity and E-cadherin. We used BS (4 mmol/L) inducing differentiation of LoVo cell and found after BS treated over 48h MS4A12 variant-1 (one of MS4A12 gene transcripts) as well as ALP and E-cadherin of LoVo cells were all increased significantly. When silence MS4A12 variant-1, the elevation of ALP and E-cadherin in BS-treated cells were all inhibited. Besides, after silence MS4A12 variant-1, the cells showed significant resistances to BS function of induction cell cycle arrest and apoptosis. Survival analysis used GEO datasets GSE39582 and GSE38832 that include 681 distinct colon cancer samples. Log-rank test and Cox's proportional hazards regression were applied to analyzing single and multiple prognostic variables, respectively. In early stage colon cancer, the patients with low MS4A12 expression had a poor survival (HR=1.72; p=0.036), while in advanced stage colon cancer MS412 had little prognostic value (HR=0.89; p=0.601). These results indicated MS4A12 might relate to colon cancer cell differentiation and supposed to be a risk classification marker for early stage colon cancer.