Exploratory study on the correlation between 14 lung cancer-related gene expression and specific clinical characteristics of NSCLC patients

Han,Yi; Li,Guo; Su,Chongyu; Ren,Hua; Chu,Xiangyang; Zhao,Qiuyue; Zhu,Yanjun; Wang,Zitong; Hu,Bin; An,Guangyu; Kang,Jingbo; Wang,Wei; Yu,Daping; Song,Xiaoyun; Xiao,Ning; Li,Yunsong; Li,Xia; Yang,Huiyi; Yu,Gang; Liu,Zhidong

doi:10.3892/mco.2013.153

Exploratory study on the correlation between 14 lung cancer-related gene expression and specific clinical characteristics of NSCLC patients

Authors:
- Yi Han
- Guo Li
- Chongyu Su
- Hua Ren
- Xiangyang Chu
- Qiuyue Zhao
- Yanjun Zhu
- Zitong Wang
- Bin Hu
- Guangyu An
- Jingbo Kang
- Wei Wang
- Daping Yu
- Xiaoyun Song
- Ning Xiao
- Yunsong Li
- Xia Li
- Huiyi Yang
- Gang Yu
- Zhidong Liu
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Affiliations: Department of Thoracic Surgery, Beijing Chest Hospital, Beijing 101149, P.R. China, Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China, General Hospital of the Chinese Armed Police Forces, Beijing 100039, P.R. China, General Hospital of the Air Force, PLA, Beijing 100142, P.R. China, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China, Navy General Hospital, Beijing 100048, P.R. China, SurExam Bio‑Tech Co. Ltd., Guangzhou Technology Innovation Base, Science City, Guangzhou 510663, P.R. China
Published online on: July 23, 2013 https://doi.org/10.3892/mco.2013.153
Pages: 887-893

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Abstract

Personalized medicine has become essential in the treatment of lung cancer. However, the lung cancer-related gene expression profiles in non-small cell lung cancer (NSCLC) patients have not been elucidated. In this study, the correlation between gene expression profiles and clinicopathological characteristics was investigated in NSCLC patients. A total of 95 patients were enrolled in this study. The mRNA expression levels of 14 genes were assessed by multiplex branched DNA liquidchip (MBL) technology and data on 9 clinicopathological characteristics of patients were collected simultaneously. The correlation between gene expression and clinicopathological characteristics was investigated. Out of the 9 clinicopathological parameters, 6 were associated with several of the 14 genes analyzed. Patient gender was associated with TYMS and TOP2A. Clinical stage was associated with VEGFR2, KIT and HER2. there was weak correlation between primary tumor size of ≤3 cm and the expression level of KIT. The mRNA expression levels of VEGFR2 and HER2 correlated with distant metastasis. BRCA1, TYMS, TOP2A and HER2 were associated with histological type. Smoking correlated with higher expression levels of BRCA1, TYMS and TOP2A and lower expression levels of PDGFRβ. The results were suggestive of correlation between the clinicopathological parameters of the NSCLC patients and the mRNA expression levels of certain lung cancer-related genes, including BRCA1, TYMS, TOP2A, PDGFRβ, VEGFR2, KIT and HER2.

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1	Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol. 2:533–543. 2001.PubMed/NCBI
2	Reardon JT, Vaisman A, Chaney SG and Sancar A: Efficient nucleotide excision repair of cisplatin, oxaliplatin, and Bis-aceto-ammine-dichloro-cyclohexylamine-platinum (IV) (JM216) platinum intrastrand DNA diadducts. Cancer Res. 59:3968–3971. 1999.
3	Lord RV, Brabender J, Gandara D, et al: Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 8:2286–2291. 2002.PubMed/NCBI
4	Hallett RM, Pond G and Hassell JA: A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy. BMC Med Genomics. 5:162012. View Article : Google Scholar : PubMed/NCBI
5	Lynch TJ, Bell DW, Sordella R, et al: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI
6	De Roock W, Claes B, Bernasconi D, et al: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 11:753–762. 2010.PubMed/NCBI
7	Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al: Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 354:809–820. 2006. View Article : Google Scholar : PubMed/NCBI
8	Flagella M, Bui S, Zheng Z, et al: A multiplex branched DNA assay for parallel quantitative gene expression profiling. Anal Biochem. 352:50–60. 2006. View Article : Google Scholar : PubMed/NCBI
9	Ren GJ, Zhao YY, Zhu YJ, et al: Tumor gene mutations and messenger RNA expression: correlation with clinical response to icotinib hydrochloride in non-small cell lung cancer. Chin Med J (Engl). 124:19–25. 2011.PubMed/NCBI
10	Asahina H, Yamazaki K, Kinoshita I, Yokouchi H, Dosaka-Akita H and Nishimura M: Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S768I and V769L. Lung Cancer. 54:419–422. 2006. View Article : Google Scholar : PubMed/NCBI
11	Olaussen KA, Dunant A, Fouret P, et al: DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 355:983–991. 2006. View Article : Google Scholar : PubMed/NCBI
12	Rosell R, Skrzypski M, Jassem E, et al: BRCA1: a novel prognostic factor in resected non-small-cell lung cancer. PLoS One. 2:e11292007. View Article : Google Scholar : PubMed/NCBI
13	Joerger M, deJong D, Burylo A, et al: Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy. Lung Cancer. 74:310–317. 2011. View Article : Google Scholar : PubMed/NCBI
14	Johnston PG, Lenz HJ, Leichman CG, et al: Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res. 55:1407–1412. 1995.PubMed/NCBI
15	Ceppi P, Volante M, Saviozzi S, et al: Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer. 107:1589–1596. 2006. View Article : Google Scholar : PubMed/NCBI
16	Nakagawa T, Otake Y, Yanagihara K, et al: Expression of thymidylate synthase is correlated with proliferative activity in non-small cell lung cancer (NSCLC). Lung Cancer. 43:145–149. 2004. View Article : Google Scholar : PubMed/NCBI
17	Bepler G, Kusmartseva I, Sharma S, et al: RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 24:4731–4737. 2006. View Article : Google Scholar : PubMed/NCBI
18	Seve P, Isaac S, Tredan O, et al: Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res. 11:5481–5486. 2005.
19	Franklin WA, Veve R, Hirsch FR, Helfrich BA and Bunn PA Jr: Epidermal growth factor receptor family in lung cancer and premalignancy. Semin Oncol. 29:3–14. 2002. View Article : Google Scholar : PubMed/NCBI
20	Jourdain L, Curmi P, Sobel A, Pantaloni D and Carlier MF: Stathmin: a tubulin-sequestering protein which forms a ternary T2S complex with two tubulin molecules. Biochemistry. 36:10817–10821. 1997. View Article : Google Scholar : PubMed/NCBI
21	Knoop AS, Knudsen H, Balslev E, et al: Retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol. 23:7483–7490. 2005.
22	Nielsen KV, Ejlertsen B, Moller S, et al: The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D. Acta Oncol. 47:725–734. 2008. View Article : Google Scholar : PubMed/NCBI
23	Lewis SJ, Cherry NM, Niven RM, Barber PV and Povey AC: Associations between smoking, GST genotypes and N7-methylguanine levels in DNA extracted from bronchial lavage cells. Mutat Res. 559:11–18. 2004. View Article : Google Scholar : PubMed/NCBI
24	Sorensen M, Autrup H, Tjonneland A, Overvad K and Raaschou-Nielsen O: Glutathione S-transferase T1 null-genotype is associated with an increased risk of lung cancer. Int J Cancer. 110:219–224. 2004. View Article : Google Scholar : PubMed/NCBI
25	Woenckhaus M, Merk J, Stoehr R, et al: Prognostic value of FHIT, CTNNB1, and MUC1 expression in non-small cell lung cancer. Hum Pathol. 39:126–136. 2008. View Article : Google Scholar : PubMed/NCBI
26	Barberis M, Pellegrini C, Cannone M, Arizzi C, Coggi G and Bosari S: Quantitative PCR and HER2 testing in breast cancer: a technical and cost-effectiveness analysis. Am J Clin Pathol. 129:563–570. 2008. View Article : Google Scholar : PubMed/NCBI
27	Nakamura H, Saji H, Ogata A, et al: Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non-small cell lung cancer. Int J Cancer. 103:61–66. 2003. View Article : Google Scholar : PubMed/NCBI
28	Cox G, Vyberg M, Melgaard B, Askaa J, Oster A and O’Byrne KJ: Herceptest: HER2 expression and gene amplification in non-small cell lung cancer. Int J Cancer. 92:480–483. 2001. View Article : Google Scholar : PubMed/NCBI
29	Nakamura H, Kawasaki N, Taguchi M and Kabasawa K: Association of HER-2 overexpression with prognosis in nonsmall cell lung carcinoma: a metaanalysis. Cancer. 103:1865–1873. 2005. View Article : Google Scholar : PubMed/NCBI
30	Sarlomo-Rikala M, Kovatich AJ, Barusevicius A and Miettinen M: CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol. 11:728–734. 1998.PubMed/NCBI
31	Heinrich MC, Corless CL, Duensing A, et al: PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 299:708–710. 2003. View Article : Google Scholar : PubMed/NCBI
32	Yamamoto H, Oda Y, Kawaguchi K, et al: c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol. 28:479–488. 2004. View Article : Google Scholar : PubMed/NCBI
33	Vlahovic G, Rabbani ZN, Herndon JE II, Dewhirst MW and Vujaskovic Z: Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR-beta and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation. Br J Cancer. 95:1013–1019. 2006. View Article : Google Scholar : PubMed/NCBI
34	Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR and Albelda SM: Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 11:3974–3986. 2005. View Article : Google Scholar : PubMed/NCBI
35	Yang JC, Haworth L, Sherry RM, et al: A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 349:427–434. 2003. View Article : Google Scholar : PubMed/NCBI
36	Paik S, Kim C and Wolmark N: HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med. 358:1409–1411. 2008. View Article : Google Scholar : PubMed/NCBI
37	Zhang YK, Yeager RL and Klaassen CD: Circadian expression profiles of drug-processing genes and transcription factors in mouse liver. Drug Metab Dispos. 37:106–115. 2009. View Article : Google Scholar : PubMed/NCBI