CMTM1_v17 is associated with chemotherapy resistance and poor prognosis in non-small cell lung cancer

Abstract

BackgroundConsidering 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.Methods31 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.ResultsCMTM1_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).ConclusionsCMTM1_v17 expression is significantly associated with chemoresistance and poor prognosis of the early stage NSCLC patients who have received NAC.

Chemokine-Like Factor-Like MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma: Latest Advances

“…The study demonstrated that CMTM1-v17 enhanced the cellular proliferation of breast cancer and prevented TNF-a-induced apoptosis by activating the NF-kB pathway. Si et al discovered that CMTM1-v17 levels in non-small cell lung carcinoma groups was much higher than in parocarcinoma tissue, which might promote the chemoresistance and lead to poor prognosis (45). Additionally, CMTM1 promoted glioblastoma cells (A172 and U251MG) proliferation and invasion which have already been verified through in vitro experiments (46).…”

CMTM family proteins 1–8: roles in cancer biological processes and potential clinical value

“…The effect of CMTM1_v17 on neoadjuvant chemotherapy (NAC) has been evaluated in a clinical study in a cohort of 78 patients with NSCLC previously treated with NAC and surgery. The expression level of CMTM1_v17 was positively correlated with higher pathological staging and lower partial response rates, thus suggesting that CMTM1_v17 expression may cause chemoresistance 15 . Moreover, Cox regression analysis indicated that expression of CMTM1_v17 in tumor tissue after NAC is an independent prognostic risk factor, and patients with high expression have poorer overall and disease-free survival outcomes than those with low expression 15 .…”

“…The CMTM family has been reported to have considerable clinical value for accessing pathological stages, determining therapeutic strategies, and predicting the outcomes of many cancer types, including breast cancer, NSCLC, and gastric cancer 15 , 16 , 42 .…”

“…The functions of CMTM family proteins in tumor growth, metastasis, and antitumor immunity are well recognized 11 – 14 . In addition, CMTM family proteins play crucial roles in mediating the clinical characteristics of tumors, including promoting chemotherapeutic resistance in non-small cell lung cancer (NSCLC) 15 , and have prognostic value in multiple cancers 15 – 18 . In this review, we focus on the CMTM family’s biological effects in tumors and potential clinical applications.…”

Research Advances in CKLF-like MARVEL Transmembrane Domain-containing Family in Non-small Cell Lung Cancer

“…Recent studies have shown that CMTM1_v17 is also highly expressed in a variety of solid tumors (breast cancer, kidney cancer, lung cancer, and ovarian cancer) and that it can activate nuclear factor-kappa B (NF-κB) signaling to promote cell proliferation and partially resist apoptosis induced by tumor necrosis factor-α [41]. Additionally, CMTM1_v17 expression is strongly linked with chemotherapy resistance and poor prognosis in early stage NSCLC patients who have received neoadjuvant chemotherapy [49]. Protein Atlas search found that lower CMTM1 expression was associated with a higher survival probability in both lung squamous cell carcinoma and adenocarcinoma (Figure 1).…”