Si Jiahui, Zhang Panpan, Tian Dan, Wang Xing, Ma Yuanyuan, Zhang Jianzhi, Wang Lu, Yang Yue
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.
Department of Immunology, School of Basic Medical Science, Health Science Center, Peking University, Beijing, 100142, China.
World J Surg Oncol. 2017 Jan 28;15(1):34. doi: 10.1186/s12957-016-1094-z.
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.
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.
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).
CMTM1_v17 expression is significantly associated with chemoresistance and poor prognosis of the early stage NSCLC patients who have received NAC.
考虑到术前新辅助化疗（NAC）可缩小并减少原发性肿瘤及远处微转移灶，从而降低高复发率，NAC已成为非小细胞肺癌（NSCLC）患者公认的治疗手段。CMTM1_v17在人类睾丸组织和实体瘤组织中高表达，但在相应正常组织中表达相对较低。本研究旨在探讨CMTM1_v17在NSCLC中的意义及其与铂类NAC疗效的关系。
利用31对NAC前后的肿瘤组织以及78例NAC后切除的肿瘤组织进行CMTM1_v17蛋白的免疫组织化学（IHC）染色。分析CMTM1_v17表达与化疗疗效之间的相关性。采用Kaplan-Meier生存分析和多变量Cox回归分析CMTM1_v17指标对无病生存期（DFS）和总生存期（OS）的预后价值。
在31例NSCLC患者中，CMTM1_v17表达与NAC后而非NAC前的肿瘤组织治疗效果及预后相关。我们发现，在这31例患者中，CMTM1_v17高表达与低客观缓解率（ORR）相关（P = 0.008）且预后较差（中位OS：35.1个月对65.6个月，P = 0.0045；中位DFS：17.27个月对35.54个月，P = 0.0207）。接下来，我们检测了78例接受NAC治疗的NSCLC患者中CMTM1_v17的表达，以证实该蛋白状态与临床特征之间的相关性。CMTM1_v17上调具有更高的疾病稳定率（P = 0.007）且预后更差（中位OS：41.0个月对80.6个月，P = 0.0028；中位DFS：33.4个月对64.8个月，P = 0.0032）。COX多变量分析表明，CMTM1_v17是接受NAC治疗患者的独立预后危险因素（OS：HR = 3.642，P = 0.002；DFS：HR = 3.094，P = 0.002）。
CMTM1_v17表达与接受NAC治疗的早期NSCLC患者的化疗耐药性及不良预后显著相关。
