Prognostic value of ribonucleotide reductase subunit M1 (RRM1) in non-small cell lung cancer: A meta-analysis

Abstract

Background: Ribonucleotide reductase subunit 1 (RRM1) is a potential prognostic factor for non-small cell lung cancer (NSCLC). This study evaluates prognostic value of RRM1 in NSCLC patients by meta-analyzing outcomes reported in literature.

Method: Data were acquired from research articles retrieved after literature search in online databases. Random effects meta-analyses were conducted by pooling hazard ratios (HR). Meta-analyses of standardized mean differences (SMD) were used to evaluate overall survival (OS) and progression-free survival (PFS) between low and high RRM1 expression groups. Metaregression analyses were conducted to evaluate the factors that could affect prognostic relationship of RRM1 with treatment and survival outcomes.

Results: 23 studies (3148 patients) were included. RRM1 expression was not meaningfully associated with prognosis of NSCLC even when the reference (HR = 1) was either low RRM1 expression (0.918 [95% CI 0.833, 1.003]) or high RRM1 expression (0.834 [0.625, 1.043]). OS was significantly longer in low RRM1 expression group compared to high RRM1 expression group (SMD 0.73 [0.36, 1.09]; P < 0.0001). PFS was not significantly different between low and high RRM1 expression groups (SMD 0.08 [-0.29, 0.45]; p = 0.68). Age was inversely associated with HR (p = 0.001) even when reference was low RRMI (p = 0.027) or high RRM1 (p = 0.006). Age was positively associated with OS in both low and high RRM1 groups.

Conclusion: In meta-analysis of studies which used gemcitabine-based therapies, higher RRM1 expression is found to associated with shorter OS but not PFS. HR depicting relationship between RRM1 expression and OS/PFS/treatment response could not demonstrate a prognostic role of RRM1 in NSCLC patients.

Keywords: Hazard; Non-small cell lung cancer; Prognosis; Ribonucleotide reductase subunit M1; Survival.