CMTM1_v17 contributes to chemotherapy resistance and predicts poor prognosis in
PUBLISHED: 2015-11-26  406 total views, 1 today

Si Jiahui, Zhang Panpan, Tian Dan

Peking University Cancer Hospital & Institute, Beijing , China,

 

Objective:CMTM1_v17 is a member of CKLFs and is highly expressed in human testis tissues and many human tumortissues and cell lines but almost undetectable in human normal tissues. This study aims to investigate correlation between the expression level of CMTM1_v17 and response to chemotherapy and outcome in non-small cell lung cancer (NSCLC). Method: We used immunochemistry to determine the expression of CMTM1_v17 in NSCLC patients. And we used flow cytometry to investigate the change of CMTM1_v17 expression in PDX model after cis-platinum treatment. Real-time PCR was used to examine the expression level of CMTM1_v17 in different cell lines. The proliferation and the inhibition of cis-platinum of A549 cells were tested by CCK8. Result: The expression of CMTM1_v17 was significantly higher in neo-adjuvant chemotherapy group than the adjuvant chemotherapy group using immunochemical staining (P=0.047). Among patients who received neo-adjuvant chemotherapy, lower CMTM1_v17 expression was associated with better prognosis (5-year overall survival rate: 80.6 % vs 41.0%, P=0.003; 5-year disease free survival rate: 64.8% vs 33.4%, P=0.003) and higher objective remission rate (ORR). But the expression of CMTM1_v17 did not affect the prognosis of patients who received adjuvant chemotherapy (5-year overall survival rate: 56.2% vs 63.2%, P=0.327; 5-year disease free survival rate: 44.0% vs 40.6%, P=0.604). COX multivariate analysis indicated that CMTM1_v17 is an independent prognostic risk factor on patients who received neo-adjuvant chemotherapy (OS:HR=3.642, P=0.002; DFS:HR=2.892, P=0.003). Patients with increased expression of CMTM1_v17 after chemotherapy had poorer prognosis and lower ORR. Flow cytometry analysis revealed that the CMTM1_v17 expression in tumors from PDX models was up-regulated after cis-platinum treatment. Real-time PCR analysis suggested that the expression of CMTM1_v17 varied among different non-small cell lung cancer cell lines at mRNA level. We found that upregulation of CMTM1_v17 could promote A549 cell proliferation and decrease the inhibition of cis-platinum in A549 cell line. Conclusion: CMTM_v17 expression was significantly associated with the prognosis of patients who received neo-adjuvant chemotherapy. Upregulation of CMTM1_v17 could promote tumor cellproliferation and decrease the sensitivity to cis-platinum.

 

Key Words: non-small cell lung cancer  neo adjuvant chemotherapy


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