Decreased expression of EFCC1 and its prognostic value in lung adenocarcinoma

Background: So far, there is a lack of reliable prognostic biomarkers for lung adenocarcinoma (ADC). Initially, we found that EF-hand and coiled-coil domain containing 1 (EFCC1) was a novel gene which was downregulated consistently with the progression of lung ADC in The Cancer Genome Atlas (TCGA) data through bioinformatics analysis. In this study, we aimed to evaluate the prognostic significance of EFCC1 in lung ADC in both TCGA data and clinical samples.

Methods: Firstly, the expression level and prognostic significance of EFCC1 in lung ADC were investigated in TCGA data. Then, the expression level of EFCC1 was validated by qPCR, Western blot, and immunohistochemistry (IHC) in five clinical lung ADC and matched adjacent non-tumor tissues. Finally, the association of EFCC1 expression with clinicopathological characteristics and overall survival (OS) in lung ADC patients was further evaluated in 130 clinical lung ADC samples with tissue microarray (TMA).

Results: In TCGA data, we found that decreased mRNA expression (P<0.001), elevated DNA methylation (P<0.001) of EFCC1 in lung ADC samples compared with normal lung samples, and low EFCC1 mRNA expression was associated with poor OS in lung ADC patients (HR =0.856, 95% CI: 0.754-0.970, P=0.015). In five clinical lung ADC and matched adjacent non-tumor tissues, both mRNA and protein levels of EFCC1 were lower in all lung ADC tissues than in their adjacent non-tumor counterparts. In 130 clinical lung ADC samples with TMA, EFCC1 expression was correlated with tumor-node-metastasis (TNM) stages (P=0.040) and lymph node metastasis status (P=0.001). The Kaplan-Meier survival curve revealed that low EFCC1 expression was significantly associated with poor OS in lung ADC patients (P=0.001) and multivariate Cox regression hazard model demonstrated that EFCC1 expression level was an independent prognostic factor for lung ADC patients (HR =0.557, 95% CI: 0.351-0.883, P=0.013).

Conclusions: Our findings suggested that decreased expression of EFCC1 was significantly associated with progression of lung ADC and could serve as a novel prognostic biomarker for lung ADC patients.