Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy

Abstract

PurposeReactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.Materials and MethodsRomo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated.ResultsA total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology.ConclusionRomo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

<p>Reactive Oxygen Species Modulator 1 is Associated with Poor Survival in Patients with Non-Small Cell Lung Cancer After Stereotactic Fractionated Radiosurgery: A Retrospective Pilot Study</p>

“…10,11 Based on these preclinical studies, clinical studies have been conducted to evaluate the clinical usefulness of Romo1 protein and it was reported that Romo1 overexpression is associated with poor survival in patients with hepatocellular carcinoma and colorectal cancer. 12,13 In addition, Romo1 overexpression was significantly associated with poor survival outcomes in patients with nonsmall cell lung cancer who received surgical resection, 14 chemotherapy, 15 and definitive radiotherapy, 16 in our previous studies. However, the clinical usefulness of Romo1 expression as a prognostic marker in patients with earlystage lung cancer who received radiosurgery has not yet been investigated.…”

“…The clinical data of 88 patients with non-small cell lung cancer who received chemotherapy were evaluated, and Romo1 overexpression was found to be associated with poor response to treatment as well as poor disease-free and overall survival. 15 In 2019, Kong et al reported that the overall, loco-regional recurrence-free and disease progression-free survival rates of the Romo1 overexpression group were significantly lower than the low Romo1 expression group in patients with stage III non-small cell lung cancer who were treated with conventional fractionated radiotherapy.…”

Overexpression of Romo1 is an unfavorable prognostic biomarker and a predictor of lymphatic metastasis in non-small cell lung cancer patients

“…Since Romo1 was first found a decade ago, there have been studies demonstrating Romo1 as a prognostic biomarker in HCC, CRC, and NSCLC, 11 , 13 , 14 but no study has investigated the mechanism by which Romo1 adversely affects prognosis of cancer patients. We have shown here that Romo1 expression is correlated with lymphatic invasion of the primary tumor, but not vascular or neural invasion; whether it is invasion of the primary tumor into lymphatics or vasculature currently depends on the lymphangiogenic or angiogenic vessels rather than the dormant vessels, 17 and the progression to lymphangiogenesis or angiogenesis depends on specific and different pro-angiogenic factors.…”

“… 10 A few studies have demonstrated the clinical application of Romo1 as a prognostic marker in NSCLC. 11 , 12 In another study, upregulated Romo1 was shown to be associated with poorer survival rate of patients with hepatocellular carcinoma (HCC) and the authors suggested that cancer invasiveness induced by Romo1 was the reason for poor survival. 13 Romo1 was also shown to have potential as an adverse prognostic marker in patients with colorectal cancer (CRC), and was reported to be associated with high lymphatic metastatic tendency.…”

Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion

“…However, we have recently demonstrated that tissue Romo1 expression was related to both poor response and prognosis in lung cancer patients who received platinum-based chemotherapy. [ 21 ]…”