Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC

Abstract

Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic modification in human cancer. Thus, detection of aberrant gene promoter methylation as a tool for diagnosis of tumors or as a prognostic marker has been widely described for many types of cancers, including nonsmall cell lung cancer (NSCLC). Emerging evidence indicates that CDH13 is a candidate tumor suppressor in several types of human tumors, including NSCLC. However, the correlation between CDH13 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In the current study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 803 NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, with the pooled odds ratio (OR) from seven studies including 448 NSCLC and 345 normal lung tissue (OR, 7.85; 95% confidence interval, 5.12–12.03; P<0.00001). CDH13 hypermethylation was also associated with pathological types. The pooled OR was obtained from four studies, including 111 squamous cell carcinoma and 106 adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19–0.66; P=0.001), which indicated that CDH13 hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13 hypermethylation had a lower survival rate than those without CDH13 hypermethylation. In addition, CDH13 mRNA high expression was found to correlate with better overall survival for all NSCLC patients followed for 20 years (hazard ratio, 0.81; P=0.0056). Interestingly, CDH13 mRNA overexpression was found to correlate with better overall survival only in adenocarcinoma patients (hazard ratio, 0.42; P=9.6e–09), not in squamous cell carcinoma patients (hazard ratio, 0.93; P=0.59). The results of this meta-analysis suggest that CDH13 hypermethylation is associated with an increased risk and worse survival in NSCLC. CDH13 hypermethylation and mRNA expression play an important role in carcinogenesis, progression, and development, as well as clinical outcomes.

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene‐induced lung tumors in aged mice

“…One tumor suppressor that is shown to be downregulated and hypermethylated in many cancers (including lung cancer) is cadherin 13 ( CDH13 ). (Andreeva & Kutuzov, 2010; Xue et al ., 2014). Based on microarray data from Kras G12D mice derived lung lesions, validation by qRT–PCR showed twofold downregulation of Cdh13 in healthy lung and lung lesions from old mice (Fig.…”

Genome-wide association study identifies four SNPs associated with response to platinum-based neoadjuvant chemotherapy for cervical cancer

“…The methylation level of RASSF1A and CDH13 promoter regions can reflect the drug sensitivity of tumors to individual treatments25. CDH13 hypermethylation is associated with increased risk and poor survival in nonsmall cell lung cancer (NSCLC)26. The hypermethylation of the CDH13 promoter is an early event in the initiation and progression of cervical neoplasia27.…”

Distinguishing Lung Adenocarcinoma from Lung Squamous Cell Carcinoma by Two Hypomethylated and Three Hypermethylated Genes: A Meta-Analysis

“…CDH13 hypermethylation was observed at higher frequency in AC than in SCC [ 23 ]. Patients with CDH13 hypermethylation tended to have lower survival [ 58 ], suggesting that CDH13 hypermethylation could serve as a prognostic biomarker in NSCLC. The current meta-analysis also confirmed this observation.…”