title: CMTM1_v17 is associated with chemotherapy resistance and poor prognosis in non-small cell lung cancer.
abstract: BACKGROUND
  Considering neoadjuvant chemotherapy (NAC) prior to surgery could shrink and reduce the primary tumor and distant micro-metastases to reduce the high relapses rates, NAC has been an accepted therapeutic management for patients with non-small cell lung cancer (NSCLC). CMTM1_v17 is highly expressed in human testis tissues and solid tumor tissues but relatively low expression was obtained in the corresponding normal tissues. This study aims to investigate the significance of CMTM1_v17 in NSCLC and its association with platinum-based NAC efficacy.
  
  
  METHODS
  31 pairs of tumor tissues before and after NAC and 78 resected tumor tissues after NAC were utilized for immunohistochemistry (IHC) staining of CMTM1_v17 protein. The correlation between CMTM1_v17 expression and chemotherapy efficacy was analyzed. The prognostic value of CMTM1_v17 index for disease-free survival (DFS) and overall survival (OS) was analyzed using Kaplan-Meier survival and multivariable Cox regression.
  
  
  RESULTS
  CMTM1_v17 expression was related to treatment effect and outcome in tumor tissues after NAC not before NAC from 31 cases of NSCLC. We identified that high CMTM1_v17 expression was associated with low objective remission rate (ORR) (P = 0.008) and poor prognosis (the median OS: 35.1 months vs 65.6 months, P = 0.0045; the median DFS: 17.27 months vs 35.54 months, P = 0.0207) in the 31 patients. Next, we detected CMTM1_v17 expression to confirm correlation between this protein status and clinical characteristics in 78 NSCLC patients with NAC treatment. The upregulation of CMTM1_v17 had a higher SD rate (P = 0.007) and worse outcome (the median OS: 41.0 months vs 80.6 months, P = 0.0028; the median DFS: 33.4 vs 64.8 months, P = 0.0032). COX multivariate analysis indicated that CMTM1_v17 is an independent prognostic risk factor on patients who have received NAC (OS: HR = 3.642, P = 0.002; DFS:HR = 3.094, P = 0.002).
  
  
  CONCLUSIONS
  CMTM1_v17 expression is significantly associated with chemoresistance and poor prognosis of the early stage NSCLC patients who have received NAC.
authors.affiliation: Department of Thoracic Surgery II, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Si
authors.affiliation: Department of Thoracic Surgery II, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery II, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Thoracic Surgery II, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery II, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery II, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Science, Health Science Center, Peking University, Beijing, 100142, China. wanglu@bjmu.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery II, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China. zlyangyue@bjmu.edu.cn.
authors.forename: Yue
authors.identifier: http://orcid.org/0000-0002-8886-7682
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D062792:MARVEL Domain-Containing Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D062792:MARVEL Domain-Containing Proteins
keywords: CMTM1_v17; Chemoresistance; Neoadjuvant chemotherapy; Non-small cell lung cancer; Prognosis