Supplementary Material for: Prognostic Impact of Reactive Oxygen Species Modulator 1 in Surgically Resected Epidermal Growth Factor Receptor-mutant Lung Adenocarcinomas

Introduction: Reactive oxygen species modulator 1 (Romo1) is a novel protein that is critically involved in intracellular production of reactive oxygen species. Evidence revealed that Romo1 is related with treatment outcomes of various human malignancies including lung cancer. However, clinical implication of this protein in surgically-resected lung cancer harboring the epidermal growth factor receptor (EGFR) mutation has not been investigated.
Methods: Data were collected from the patients who underwent curative resection for EGFR-mutant lung adenocarcinoma. Romo1 protein expression level was measured in the resected tumor tissue using immunohitochemical staining and evaluated semiquantatively using histochemical score (H score). Univariate and multivariate analyses were performed to identify clinicopathological parameters that may be associated with clinical outcomes.
Results: A total of 98 samples were analyzed. Using the cutoff H score 150, the population was classified into low (n=73) and high (n=25) Romo1 groups. Romo1 expression was significantly higher in smokers, patients with stage III disease, and patient who experienced recurrence after surgery (all p<0.05). In the multivariate analyses, advanced stage and poorly differentiated cancer were associated with shorter disease-free survival (DFS). In addition, high Romo1 expression was independently associated with poor DFS (hazard ratio [HR] = 2.20, 95% confidence interval [CI]:1.10–5.42, p = 0.0324).
Conclusions: Our data showed that Romo1 overexpression was significantly associated with early recurrence in patients with resected, EGFR-mutant lung adenocarcinoma. Although large-scaled data are needed, Romo1 may have prognostic role for this patient population.

引言：活性氧调控蛋白1（Romo1）是一种新型蛋白，在细胞内活性氧（Reactive oxygen species）的生成过程中发挥关键调控作用。现有研究表明，Romo1与包括肺癌在内的多种人类恶性肿瘤的治疗结局密切相关。然而，该蛋白在表皮生长因子受体（epidermal growth factor receptor, EGFR）突变型手术切除肺癌中的临床意义尚未得到深入研究。
方法：本研究收集了接受根治性切除术的EGFR突变型肺腺癌患者的临床资料。采用免疫组化染色法检测手术切除的肿瘤组织中Romo1蛋白的表达水平，并通过组织化学评分（H score）进行半定量评估。采用单因素及多因素分析，筛选可能与临床结局相关的临床病理参数。
结果：本研究共纳入98例样本进行分析。以H评分临界值150为界，将研究对象分为Romo1低表达组（n=73）和高表达组（n=25）。Romo1表达水平在吸烟者、Ⅲ期疾病患者以及术后复发患者中显著升高（所有p<0.05）。多因素分析结果显示，临床分期较晚及肿瘤低分化与更短的无病生存期（disease-free survival, DFS）相关。此外，Romo1高表达是无病生存期较差的独立危险因素（风险比[HR]=2.20，95%置信区间[CI]：1.10~5.42，p=0.0324）。
结论：本研究数据显示，Romo1过表达与接受手术切除的EGFR突变型肺腺癌患者的早期复发显著相关。尽管仍需开展大样本量研究进一步验证，但Romo1有望成为该患者群体的潜在预后标志物。