The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma

Abstract

Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. However, the prognostic role of concordant overexpression of synthetic lethality genes in protein level rather than a combination of mutations is not clear. In this study, we explore the prognostic role of combined overexpression of paired genes in lung adenocarcinoma. We used immunohistochemical staining to investigate 24 paired genes in 93 lung adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis (HR = 2.35, P = 0.0230). These results suggest that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B.

Fig 1. Representative IHC staining of FEN1 and RAD54B in lung adenocarcinoma tissues.

(a) and (b): Both positive FEN-1 and RAD54B nuclear staining; (c)and (d): Both negative FEN-1 and RAD54B nuclear staining; (e)and (f): Negative FEN-1 and positive RAD54B nuclear staining.

Fig 2. Overall survival of lung adenocarcinoma patients based on expression or lack of expression of FEN1 and RAD54B expressions.

Blue line: FEN1(-) and RAD54B(-); Green line: FEN1(+) and RAD54B(-); Red line: FEN1(-) and RAD54B(+); Black line: FEN1(+)and RAD54B(+).