Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose Reactive 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 platinumbased chemotherapy. Materials and Methods Romo1 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. Results A 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. Conclusion Romo1 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.
Abstract
Purpose Reactive 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 platinumbased chemotherapy. Materials and Methods Romo1 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. Results A 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. Conclusion Romo1 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.
참고문헌 (25)
- Jemal A, "Global burden of cancer : opportunities for prevention", Lancet, 380, pp.1797~1799 (2012)
- DeSantis CE, "Cancer treatment and survivorship statistics, 2014", CA Cancer J Clin, 64, pp.252~271 (2014)
- Schiller JH, "Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer", N Engl J Med, 346, pp.92~98 (2002)
- Slebos RJ, "K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung", N Engl J Med, 323, pp.561~565 (1990)
- Tsao MS, "Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer", J Clin Oncol, 25, pp.5240~5247 (2007)
- Miller VA, "Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib", J Clin Oncol, 26, pp.1472~1478 (2008)
- Roberts PJ, "KRAS mutation: should we test for it, and does it matter", J Clin Oncol, 31, pp.1112~1121 (2013)
- Altaha R, "Excision repair cross complementing-group 1 : gene expression and platinum resistance", Int J Mol Med, 14, pp.959~970 (2004)
- Rosell R, "DNA repair and cisplatin resistance in non-small-cell lung cancer", Lung Cancer, 38, pp.217~227 (2002)
- Lord RV, "Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer", Clin Cancer Res, 8, pp.2286~2291 (2002)
- Olaussen KA, "DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy", N Engl J Med, 355, pp.983~991 (2006)
- Simon GR, "ERCC1expression is a predictor of survival in resected patients with non-small cell lung cancer", Chest, 127, pp.978~983 (2005)
- Cobo M, "Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression : a phase III trial in non-small-cell lung cancer", J Clin Oncol, 25, pp.2747~2754 (2007)
- Chung YM, "A novel protein, Romo1, induces ROS production in the mitochondria", Biochem Biophys Res Commun, 347, pp.649~655 (2006)
- Na AR, "A critical role for Romo1-derived ROS in cell proliferation", Biochem Biophys Res Commun, 369, pp.672~678 (2008)
- Hwang IT, "Drug resistance to 5-FU linked to reactive oxygen species modulator 1", Biochem Biophys Res Commun, 359, pp.304~310 (2007)
- Lee SH, "Serum reactive oxygen species modulator 1(Romo1)as a potential diagnostic biomarker for non-small cell lung cancer", Lung Cancer, 85, pp.175~181 (2014)
- Lee SH, "Reactive oxygen species modulator 1(Romo1)overexpression is an independent predictor of poor survival in NSCLC patients who undergo surgical resection", Lung Cancer, 87, pp.45~52 (2015)
- Eisenhauer EA, "New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)", Eur J Cancer, 45, pp.228~247 (2009)
- Chung YM, "Replicative senescence induced by Romo1-derived reactive oxygen species", J Biol Chem, 283, pp.33763~33771 (2008)
- Chung JS, "Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells", Gastroenterology, 143, pp.1084~1094 (2012)
- Sosa V, "Oxidative stress and cancer : an overview", Ageing Res Rev, 12, pp.376~390 (2013)
- Pelicano H, "ROS stress in cancer cells and therapeutic implications", Drug Resist Updat, 7, pp.97~110 (2004)
- Chung JS, "Mitochondrial reactive oxygen species originating from Romo1 exert an important role in normal cell cycle progression by regulating p27(Kip1)expression", Free Radic Res, 43, pp.729~737 (2009)
- Mok TS, "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma", N Engl J Med, 361, pp.947~957 (2009)
