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

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    https://www.riss.kr/link?id=A103570362

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    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.
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    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 expr...

    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.

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    참고문헌 (Reference)

    1 Lee SH, "Serum reactive oxygen species modulator 1(Romo1)as a potential diagnostic biomarker for non-small cell lung cancer" 85 : 175-181, 2014

    2 Chung YM, "Replicative senescence induced by Romo1-derived reactive oxygen species" 283 : 33763-33771, 2008

    3 Lee SH, "Reactive oxygen species modulator 1(Romo1)overexpression is an independent predictor of poor survival in NSCLC patients who undergo surgical resection" 87 : 45-52, 2015

    4 Pelicano H, "ROS stress in cancer cells and therapeutic implications" 7 : 97-110, 2004

    5 Tsao MS, "Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer" 25 : 5240-5247, 2007

    6 Sosa V, "Oxidative stress and cancer : an overview" 12 : 376-390, 2013

    7 Chung JS, "Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells" 143 : 1084-1094, 2012

    8 Eisenhauer EA, "New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)" 45 : 228-247, 2009

    9 Miller VA, "Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib" 26 : 1472-1478, 2008

    10 Chung JS, "Mitochondrial reactive oxygen species originating from Romo1 exert an important role in normal cell cycle progression by regulating p27(Kip1)expression" 43 : 729-737, 2009

    1 Lee SH, "Serum reactive oxygen species modulator 1(Romo1)as a potential diagnostic biomarker for non-small cell lung cancer" 85 : 175-181, 2014

    2 Chung YM, "Replicative senescence induced by Romo1-derived reactive oxygen species" 283 : 33763-33771, 2008

    3 Lee SH, "Reactive oxygen species modulator 1(Romo1)overexpression is an independent predictor of poor survival in NSCLC patients who undergo surgical resection" 87 : 45-52, 2015

    4 Pelicano H, "ROS stress in cancer cells and therapeutic implications" 7 : 97-110, 2004

    5 Tsao MS, "Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer" 25 : 5240-5247, 2007

    6 Sosa V, "Oxidative stress and cancer : an overview" 12 : 376-390, 2013

    7 Chung JS, "Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells" 143 : 1084-1094, 2012

    8 Eisenhauer EA, "New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)" 45 : 228-247, 2009

    9 Miller VA, "Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib" 26 : 1472-1478, 2008

    10 Chung JS, "Mitochondrial reactive oxygen species originating from Romo1 exert an important role in normal cell cycle progression by regulating p27(Kip1)expression" 43 : 729-737, 2009

    11 Lord RV, "Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer" 8 : 2286-2291, 2002

    12 Roberts PJ, "KRAS mutation: should we test for it, and does it matter" 31 : 1112-1121, 2013

    13 Slebos RJ, "K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung" 323 : 561-565, 1990

    14 Jemal A, "Global burden of cancer : opportunities for prevention" 380 : 1797-1799, 2012

    15 Mok TS, "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma" 361 : 947-957, 2009

    16 Altaha R, "Excision repair cross complementing-group 1 : gene expression and platinum resistance" 14 : 959-970, 2004

    17 Simon GR, "ERCC1expression is a predictor of survival in resected patients with non-small cell lung cancer" 127 : 978-983, 2005

    18 Hwang IT, "Drug resistance to 5-FU linked to reactive oxygen species modulator 1" 359 : 304-310, 2007

    19 Olaussen KA, "DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy" 355 : 983-991, 2006

    20 Rosell R, "DNA repair and cisplatin resistance in non-small-cell lung cancer" 38 : 217-227, 2002

    21 Cobo M, "Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression : a phase III trial in non-small-cell lung cancer" 25 : 2747-2754, 2007

    22 Schiller JH, "Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer" 346 : 92-98, 2002

    23 DeSantis CE, "Cancer treatment and survivorship statistics, 2014" 64 : 252-271, 2014

    24 Chung YM, "A novel protein, Romo1, induces ROS production in the mitochondria" 347 : 649-655, 2006

    25 Na AR, "A critical role for Romo1-derived ROS in cell proliferation" 369 : 672-678, 2008

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