Gene Expression Profiling for Cancer Targeted Therapy
Abstract
Background: Lung cancer is still the leading cause of cancer- related deaths and most of them are normally diagnosed in late stages, So there is an urgent need to establish reliable tools for the identification at early stages of the disease. In this study, we use an eleven gene signature test to examine lung biopsy specimens for diagnostic, prognostic & therapeutic purposes.Methods: Bronchoscopy was performed to collect 102 fresh frozen specimens from 51 patients. 32 lung tumors & their adjacent normal tissues were examined along with biopsy specimens. In all specimens, total RNAs were isolated & after generating cDNA, were used for qRT-PCR analysis.Results: The results indicate that the expressions of 3 oncogenes Bcl-2, k-ras & h-ras were significantly high (p<0.05) in surgically removed tumors as well as biopsy specimens compare to adjacent normal tissues. The differential expressions of these 3 genes were strikingly higher in cigarette using patients than nonsmokers.Conclusion: Considering the overall results of this study, it can be concluded that, lung tissue abnormalities other than cancer could cause the elevation of some oncogene expression. This study also verifies that smoking can definitely cause oncogenic mutation, activation &/or amplification; which is now a globally proven fact.Spiro SG, Silvestri GA. One hundred years of lung cancer. Am JRespir Crit Care Med.2005; 172: 523–529.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer.CA Cancer J Clin. 2008; 58:71–96.
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell. N Engl J Med. 2006; 355:2542–50.
Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP,Miettinen OS. Survival of patients with stage I lung cancer detected onCT screening. N Engl J Med. 2006;355:1763–71.
Bach PB, Silvestri GA, Hanger M, Jett JR. Screening for lung cancer:ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132:69S-77S.
Roland R R. Population genetics meets cancer genomics. PNAS. 2010; 107 (43): 18241-1824.
Sager R, Sheng S, Anisowicz A, Sotiropoulou G, Zou Z, Stenman G, Swisshelm K, Chen Z, Hendrix M J C, PembertonP, Rafid K,Ryan K.Cold Spring Harbor Symp. Quant. Biol. 1994; 59, 537–546.
Cooper GM. Oncogenes 2nd edition (Jones & Bartlett, publishers). 1995.
Weinberg RA. How Cancer arises. Sci. Am. 1996; 275, 62–70.
Bishop J M.Molecular themes in oncogenesis. Cell. 1991; 64, 235– 248.
Erika Check Hayden. Personalized Cancer Therapy. Nature. 2009;458: 131-132.
Ken Carber. ALK Lung cancer and Personalized Therapy. JNCI. 2010; 102: 672-675.
Roberts PJ, Stinchcombe TE, Der CJ, Socinski MA.Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in se- lecting patients for epidermal growth factor receptor-targeted therapy.J Clin Oncol. 2010; 1: 28(31):4769-77.
DaltonWS, Friend SH. Cancer biomarkers-an invitation to the table. Science. 2006; 312:1165-1168.
Beer DG, Kardia SL, Huang CC, et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. NatMed. 2002; 8:816-824.
BhattacharjeeA, RichardsWG, StauntonJ, et al. Classification of hu- man lung carcinomas by mRNAexpression profiling reveals distinct ad- enocarcinoma subclasses. Proc Natl Acad Sci U S A. 2001;98:13790-5.
Larsen JE, Pavey SJ, Passmore LH, Bowman RV,Hayward NK, Fong KM. Gene expression signature predicts recurrence in lung ad- enocarcinoma. Clin Cancer Res. 2007;13:2946-54.
Chen HY, Yu SL, Chen CH, et al. A five-gene signature and clini- cal outcome in non-small-cell lung cancer. NEngl JMed.2007;356:1120.
Potti A, Mukherjee S, Petersen R, et al. A genomic strategy to refine prognosis in early-stage non-smallcell lung cancer. NEngl JMed.2006;355:570-8.
Hayes DN, Monti S, Parmigiani G, et al. Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts. J Clin Oncol. 2006;24:5079-90.
Von Hoff DD, et al. Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol, 2010 Nov; 28(33):4877-83.
Suzuki Y, Orita M, Shiraishi M, Hayashi K, Sekiya T. Detection of ras gene mutations in human lung cancers by single-strand confor- mation polymorphism analysis of polymerase chain reaction products. Oncogene.1990; 5: 1037-1043.
Mitsudomi T, Viallet J, Mulshine JL, Linnoila RI, Minna JD, Gaz- dar AF. Mutations of ras genes distinguish a subset of non-small-cell lung cancer cell lines from small-cell lung cancer cell lines. Onco- gene.1991;6: 1353-1362.
Alemany R, Ruan S, Kataoka M, Koch PE, Mukhopadhyay T, Cris- tiano RJ. Growth inhibitory effect of anti-K-ras adenovirus on lung can- cer cells. Cancer Gene Therapy. 1996; 3: 296-301.
Yoshimoto K, Shiraishi M, Hirohashi S, Morinaga S, Shimosato Y, Sugimura T, Sekiya T, Rearrangement of the c-myc gene in two giant cell carcinomas of the lung. Jpn J Cancer Res. 1986; 77: 731-735.
Usuda J, Ichinose S, Ishizumi T, Ohtani K, Inoue T, Maehara S, Imai K, Shima K, Ohira T, Kato H, Ikeda N. Molecular determinants of photodynamic therapy for lung cancers. Lasers Surg Med. 2011 Sep;43(7):591-9.
Lara PN JR, Laptalo L, Longmate J, Lau DH, Gandour-Edwards R, Gumerlock PH, Doroshow JH, Gandara DR.Trastuzumab plus docetax- el in HER2/neu-positive non-small-cell lung cancer: a California Can- cer Consortium screening and phase II trial. Clin Lung Cancer.2004 Jan;5(4):231-6.
Samanthi A. Pereraa,b, Danan Lia,b, Takeshi Shimamuraa, Maria G. Rasoc, Hongbin Jid, Liang Chena,b, Christa L. Borgmana,Sara Za- ghlula, Kathleyn A. Brandstettera, Shigeto Kuboe, Masaya Takahashie, Lucian R. Chirieacf, Robert F. Paderaf, Roderick T.Bronsong, Geoffrey I. Shapiroa, Heidi Greulicha,h, Matthew Meyersona,h, Ulri Guertleri, Pilar Garin Chesai,Flavio Solca, Ignacio I. Wistuba, and Kwok-Kin Wong. HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combi- nation therapy. PNAS. 2009; 106 (2): 474-479
Wenjuan Wu, Michael S. O’Reilly, Robert R. Langley, Rachel Z. Tsan, Cheryl H. Baker, Neby Bekele, Xi Ming Tang, Amir Onn, Isaiah J. Fidler and Roy S. Herbst. Expression of epidermal growth factor (EGF)/ transforming growth factor-α by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice. Molecular Cancer Therapeutics.2007;6:2652-2663.
Kishimoto Y, Murakami Y, Shiraishi M, Hayashi K, Sekiya T. Ab- errations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung. Cancer Res. 1992;52: 4799-4804.
Hollstein M,Sidransky D, Vogelstein B,Harris CC. p53 mutations in human cancers, Science.1991; 253: 49-53.
Reiss M,. Brash DE, Munoz-Antonia T,. Simon JA,Ziegler A,Vellucci VF, Zhou ZL. Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines. Oncol Res. 1992; 4: 349-357.
Leach FS, Tokino T, Meltzer P, Burrell M, Oliner MJD, Smith S,Hill DE, Sidransky D,. Kinzler KW, Vogelstein B, p53 Mutation and MDM2 amplification in human soft tissue sarcomas,.Cancer Res. 1993; 53: 2231-2234.
Sauter W, Rosenberger A, Beckmann L, Kropp S, Mittelstrass K, Timofeeva M, Wölke G, Steinwachs A, Scheiner D, Meese E, Sybrecht G, Kronenberg F, Dienemann H; LUCY-Consortium, Chang-Claude J, Illig T, Wichmann HE, Bickeböller H, Risch A.Matrix metalloprotein- ase 1 (MMP1) is associated with early-onset lung cancer.Cancer Epide- miol Biomarkers Prev. 2008 May;17(5):1127-35.
Deshmukh HS, McLachlan A, Atkinson JJ, Hardie WD, Korfhagen TR, Dietsch M, Liu Y, Di PY, Wesselkamper SC, Borchers MT, Leikauf GD.Matrix metalloproteinase-14 mediates a phenotypic shift in the air- ways to increase mucin production.Am J Respir Crit Care Med. 2009 Nov 1;180(9):834-45.
Wang YL, Yan YL, Zhou NJ, Han S, Zhao JX, Cao CL, Lü YH. Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP. Chin Med J (Engl). 2010 Nov;123(22):3299-303.
Takakuwa O, Oguri T, Ozasa H, Uemura T, Kasai D, Miyazaki M, Maeno K, Sato S. Over-expression of MDR1 in amrubicinol-resistant lung cancer cells. Cancer Chemother Pharmacol. 2011 Sep;68(3):669- 76.
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Issue | Vol 4 No 3&4 (2012) | |
Section | Original Articles | |
Keywords | ||
Lung biopsy specimen Gene expressionprofiling |
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