Protein expression of close homologue of L1 (CHL1) is a marker for overall survival in non-small cell lung cancer (NSCLC)

J Cancer Res Clin Oncol. 2019 Sep;145(9):2285-2292. doi: 10.1007/s00432-019-02989-x. Epub 2019 Aug 1.

Abstract

Background: The cell adhesion molecule close homologue of L1 (CHL1) is a potential tumour suppressor and was recently detected in non-small cell lung cancer (NSCLC) specimens. The expression pattern, prognostic, and functional role of CHL1 in NSCLCs is unknown.

Methods: We evaluated the protein expression of CHL1 by immunohistochemistry in 2161 NSCLC patients based on a tissue microarray. The results were correlated with clinical, histopathological, and patient survival data (Chi square test, t test, and log-rank test, respectively). A multivariate analysis (Cox regression) was performed to validate its impact on patients' survival.

Results: CHL1 was expressed in NSCLC patients and was significantly overexpressed in lung adenocarcinomas and squamous cell carcinomas compared to neuroendocrine and large cell carcinomas of the lung (p < 0.001). CHL1 expression was associated with the T stage in adenocarcinomas (p = 0.011) and with metastatic lymph node status and UICC stage in squamous cell carcinomas (p = 0.034 and p = 0.035, respectively). Increased CHL1 expression was associated with improved survival in univariate (p = 0.031) and multivariate analyses (odds ratio 0.797, 95% confidence interval 0.677-0.939, p = 0.007).

Conclusion: The prognostic significance of CHL1 makes it a potential prognostic and therapeutic target and underlines its role as a tumour suppressor. Further validation studies and functional analyses are needed to investigate its potential role in tumourigenesis and dissemination.

Keywords: CHL1; L1; Lung cancer; NSCLC; Prognostic maker; Tumour marker.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion Molecules / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • CHL1 protein, human
  • Cell Adhesion Molecules