title: Serum reactive oxygen species modulator 1 (Romo1) as a potential diagnostic biomarker for non-small cell lung cancer.
abstract: OBJECTIVE
  Reactive oxygen species modulator 1 (Romo1) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. Romo1 is increased in most cancer cell lines and is related with resistance to chemotherapy in vitro. However, data on its expression in patients with malignancy is very limited. We evaluated the usefulness of serum Romo1 as a potential diagnostic biomarker in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We initially assessed the expression of Romo1 using Western blotting and enzyme-linked immunosorbent assay in paired lung tissue and serum specimen from NSCLC patients who underwent surgical resection. Then we evaluated and compared serum Romo1 level in a healthy population (n=55), patients with benign lung diseases (n=63) and NSCLC patients (n=58). We explored the correlation between Romo1 expression and clinical parameters and assessed diagnostic performance of serum Romo1 for NSCLC using receiver operating characteristic (ROC) curve analysis.
  
  
  RESULTS
  Romo1 expression in lung cancer tissues was significantly increased compared with non-tumorous tissues (p<0.001). Romo1 expression in cancer tissues positively correlated with that in serum (r=0.68, p=0.009). Serum Romo1 level in NSCLC patients significantly increased compared with that of healthy population or patients with benign lung diseases (both p<0.001). ROC curve analysis using an optimal cutoff value of 329.7 pg/mL revealed sensitivity and specificity for the diagnosis of NSCLC of 81.9% and 89.8%, respectively, with an area under the curve of 0.847 (95% confidence interval: 0.789-0.892, p<0.001). Serum Romo1 level was not related with age, gender, smoking status, tumor differentiation, histological type or stage.
  
  
  CONCLUSIONS
  Serum Romo1 discriminated NSCLC patients from the population without cancer with considerable sensitivity and specificity. Serum Romo1 could be a potential diagnostic biomarker for NSCLC.
authors.affiliation: Department of Internal Medicine, KEPCO Medical Center, Seoul, Republic of Korea.
authors.forename: Seung Hyeun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Biostatistical Consulting Unit, Sunchunhyang University Medical Center, Seoul, Republic of Korea.
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Gyu Young
authors.initials: GY
authors.lastname: Hur
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea. Electronic address: khin@kumc.or.kr.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000097:blood*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012907:Smoking
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C513338:ROMO1 protein, human
keywords: Biomarker; Diagnosis; Non-small cell lung cancer; Oxidative stress; Reactive oxygen species; Serum