Reactive oxygen species modulator 1 expression predicts lymph node metastasis and survival in early-stage non-small cell lung cancer.

Taehee Kim,Yong Jun Choi,Yoon Jin Cha,Arum Kim,Ji Hyun Park,Hye Jung Park,Jung Weon Lee

doi:10.1371/journal.pone.0239670

Abstract

Reactive oxygen species modulator 1 (romo1) causes cell hyperplasia and promotes cancer cell invasion. Based recent studies, the overexpression of romo1 is associated with lymphatic metastasis and poor prognosis in lung cancer. We aimed to evaluate associations between romo1 expression and lymph node metastasis in non-small cell lung cancer (NSCLC). Clinical data and pathological results were retrospectively reviewed for 98 subjects diagnosed with NSCLC and who underwent surgical biopsy between 1994 and 2009. A total 98 tumor specimens were analyzed. The romo1 H score was correlated with stage and was significantly higher in subjects with lymph node metastasis than in those without metastasis (173 vs 116; P < 0.05). The area (%) of grade 1 expression was significantly smaller (19.5 vs 37.0; P = 0.005) and the area of grade 3 expression was significantly larger (27.9 vs 6.00; P < 0.001) in subjects with lymph node metastasis than in those without metastasis. In stage I patients, disease free survival (DFS) (191 ± 18.8 vs. 75.6 ± 22.4 months, P = 0.004) was significantly longer in the low romo1 group than in the high romo1 group. A multivariate analysis showed a significant association between high romo1 expression and poor DFS (hazard ratio 5.59, 95 confidence interval, 1.54–20.3, P = 0.009). These findings support the prognostic value of romo1 in NSCLC, especially in stage I.

Highlights

Reactive oxygen species modulator 1 is a non-selective cation channel present on the surface of mitochondria and it produces reactive oxygen species (ROS) by oxidative stress [1, 2]
Romo1 was primarily localized to the cytoplasm of cancer cells, regardless of type of non-small cell lung cancer (NSCLC)
Using data from NSCLC subjects who underwent surgical biopsy, we demonstrated that the expression of romo1 increases according to stage, especially in the presence of lymph node metastasis

Summary

Introduction

Reactive oxygen species modulator 1 (romo1) is a non-selective cation channel present on the surface of mitochondria and it produces reactive oxygen species (ROS) by oxidative stress [1, 2]. Increased ROS production by romo alters intracellular oxidative stress homeostasis, thereby inducing DNA damage and genomic instability [1]. Romo expression predicts LN metastasis in early NSCLC minimize toxicity induced by ROS. ROS production often exceeds the antioxidant capacity, leading to cell death, inflammation, or cancer cell production [3]. The overexpression of romo is frequently observed in various cancer cell lines. Increased ROS production induced by romo overexpression can cause persistent oxidative stress, increase malignancy, and promote cancer development and progression [4]

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