title: Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance.
abstract: OBJECTIVE
  The assessment of single gene such as ERCC1, TYMS, RRM1, TUBB3, EGFR, KRAS, BRAF, PIK3CA, ALK, and ROS1 is now widely applied in therapeutic decisions of non-small cell lung cancer (NSCLC). The aim of our study was to concurrently analyze these genes and evaluate their clinical significance in patients with NSCLC.
  
  
  METHODS
  Rearrangement of ALK and ROS1 was analyzed in 120 patients using FISH assays. Somatic mutation of EGFR, KRAS, BRAF, PIK3CA and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR were examined by liquidchip platform in 350 patients . Data on clinical features were obtained from medical records of 119 patients, and the follow-up was conducted in 106 patients who received platinum-based adjuvant chemotherapy.
  
  
  RESULTS
  We identified 5.0% ALK rearrangements, 1.7% ROS1 rearrangements, 36.6% EGFR mutations, 8.9% KRAS mutations, 0% BRAF mutations, and 4.0% PIK3CA mutations. Double or coexisting mutations were identified in 13 patients. Significant correlations were observed among EGFR, KRAS mutation, ERCC1, TYMS, RRM1, TUBB3, EGFR expression, and clinical features, especially histology (P < 0.05). Significant cross-correlations were observed in some pairs of genes (P < 0.05). Patients with low RRM1 expression had a better progression-free survival (PFS) (P < 0.05). Furthermore, EGFR-mutated patients with low RRM1 expression or patients with both ERCC1 and RRM1 low expression had a better PFS (P < 0.05).
  
  
  CONCLUSIONS
  Combined analysis of these commonly studied genes may promote the individual treatment in NSCLC. RRM1 may be a prognostic and predictive biomarker for PFS in patients with NSCLC who received platinum-based adjuvant chemotherapy, and combining EGFR mutation and RRM1 expression or combining ERCC1 and RRM1 expression can enhance prognostic and predictive power for PFS.
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Quan
authors: Q
authors: Zhang
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Tianyu
authors: T
authors: Sun
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Poming
authors: P
authors: Kang
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Kai
authors: K
authors: Qian
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Bo
authors: B
authors: Deng
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Jinghai
authors: J
authors: Zhou
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Ruwen
authors: R
authors: Wang
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Bin
authors: B
authors: Jiang
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors: Kun
authors: K
authors: Li
authors: SurExam Bio-Tech, Guangzhou Technology Innovation Base, 80 Lan Yue Road, Science City, Guangzhou, People's Republic of China.
authors: Fang
authors: F
authors: Liu
authors: SurExam Bio-Tech, Guangzhou Technology Innovation Base, 80 Lan Yue Road, Science City, Guangzhou, People's Republic of China.
authors: Shiyang
authors: S
authors: Wu
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China. qunyoutan@sina.com.
authors: Qunyou
authors: Q
authors: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017671:Platinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D017671:Platinum Compounds; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: ALK; EGFR; ERCC1; Non-small cell lung cancer; Progression-free survival; RRM1