Abstract
PurposeReactive oxygen species modulator 1 (Romo1) is a novel protein that regulates the production of intracellular reactive oxygen species. Romo1 has been shown to be associated with poor survival in various clinical settings for the treatment of lung cancer. In this study, we evaluated whether tissue Romo1 expression was associated with clinical outcomes in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs).MethodRomo1 expression in tumor tissues was examined by immunohistochemistry and evaluated by histologic score. Univariate and multivariate analyses were performed to identify the clinicopathologic parameters, including Romo1 expression, which may be associated with progression-free survival (PFS), overall survival (OS), and incidence of secondary T790M mutation.ResultsA total of 96 tumor specimens were analyzed. With the cut-off value of 200, 71 (74.0%) and 25 (26.0%) patients were classified into low and high Romo1 groups, respectively. The median PFS of the high Romo1 group was significantly shorter than that of the low Romo1 group (13.1 vs 19.9 months, p = 0.0165). The median OS of the high Romo1 group was also significantly shorter than that of the low Romo1 group (19.8 vs 37.0 months, p = 0.0006). Multivariate analyses showed that high Romo1 expression was independently associated with both poor PFS (hazard ratio [HR] = 2.48, 95% confidence interval [CI]: 1.35–4.56, p = 0.0034) and poor OS (HR = 3.17, 95% CI: 1.57–6.41, p = 0.0013). In addition, the rate of secondary T790M mutation after TKI failure was significantly lower in the high Romo1 group than the low Romo1 group (16.7% vs. 38.3%, p = 0.0369).ConclusionsRomo1 overexpression was associated with poor response to treatment and short survival in patients treated with EGFR-TKIs, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach. In addition, our data highlight that Romo1 could be a potential predictive and prognostic biomarker for this patient population.
Highlights
Lung cancer has been the leading cause of cancer-related deaths worldwide
Located in the mitochondrial membrane, this novel protein is a major regulator of the production of intracellular reactive oxygen species (ROS), and Reactive oxygen species modulator 1 (Romo1)-induced ROS play a significant role in cell proliferation in both cancer and normal cells [6, 7]
We investigated whether Romo1 expression is related with the response to treatment, survival rate, and the development of secondary T790M mutations after tyrosine kinase inhibitors (TKIs) failure
Summary
Lung cancer has been the leading cause of cancer-related deaths worldwide. Globally, it accounted for 2.2 million new cases and 1.8 million deaths in 2020 [1]. Romo1-induced ROS are related to the drug resistance of 5-fluorouracil (5-FU), and Romo overexpression induces invasive activity in various cancer cells [8,9,10] These findings suggest that Romo may be involved in carcinogenesis but may influence the response to anticancer treatment. Kim et al reported that elevated Romo expression in curatively resected colorectal cancer was significantly associated with poor survival outcomes and frequent lymph node metastasis [13]. These data suggest that Romo is a promising biomarker for malignancies. The clinical usefulness of this protein has never been explored in patients with cancer harboring driver genetic alterations
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