OBJECTIVE: We hypothesized that clinical outcome of resected early-stage adenocarcinoma of the lung can be predicted by the expression of a few critically important genes as measured by quantitative real-time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary tumors. METHODS: Twenty-two prognostic genes for the metastatic phenotype were identified through complementary DNA microarray analysis of 4 cancer cell lines and bioinformatics analysis. Expression levels of a subset of these genes (n = 13) were measured by real-time time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary adenocarcinoma from patients whose disease recurred within 2 years (n = 9) and in patients who did not have a recurrence (n = 11). Receiver operating characteristic curves were analyzed to establish prognostic values of single genes. The most informative gene was combined with the remaining genes to determine whether there was a particular pair(s) that yielded high diagnostic accuracy. A small validation study was performed. RESULTS: Receiver operating characteristic curve analysis of the single genes revealed that high expression of CK19 was associated with nonrecurrence (area under the curve = 0.859, confidence interval = 0.651-0.970). The CK19/EpCAM2 gene ratio had the most reproducible prognostic accuracy, followed by the CK19/P-cadherin ratio. A Kaplan-Meier survival analysis generated from the CK19/EpCAM2 ratio resulted in highly significant curves as a function of marker positivity (P = .0007; hazard ratio = 10.7). Significance declined but was maintained in the validation study. CONCLUSIONS: This preliminary study provides evidence that the CK19/EpCAM2 and/or CK19/P-cadherin ratio(s) may be a simple and accurate prognostic indicator of clinical outcome in early-stage adenocarcinoma of the lung. If further validation studies from large patient cohorts confirm the results, adjuvant therapy could be targeted to this high-risk group.
OBJECTIVE: We hypothesized that clinical outcome of resected early-stage adenocarcinoma of the lung can be predicted by the expression of a few critically important genes as measured by quantitative real-time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary tumors. METHODS: Twenty-two prognostic genes for the metastatic phenotype were identified through complementary DNA microarray analysis of 4 cancer cell lines and bioinformatics analysis. Expression levels of a subset of these genes (n = 13) were measured by real-time time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary adenocarcinoma from patients whose disease recurred within 2 years (n = 9) and in patients who did not have a recurrence (n = 11). Receiver operating characteristic curves were analyzed to establish prognostic values of single genes. The most informative gene was combined with the remaining genes to determine whether there was a particular pair(s) that yielded high diagnostic accuracy. A small validation study was performed. RESULTS: Receiver operating characteristic curve analysis of the single genes revealed that high expression of CK19 was associated with nonrecurrence (area under the curve = 0.859, confidence interval = 0.651-0.970). The CK19/EpCAM2 gene ratio had the most reproducible prognostic accuracy, followed by the CK19/P-cadherin ratio. A Kaplan-Meier survival analysis generated from the CK19/EpCAM2 ratio resulted in highly significant curves as a function of marker positivity (P = .0007; hazard ratio = 10.7). Significance declined but was maintained in the validation study. CONCLUSIONS: This preliminary study provides evidence that the CK19/EpCAM2 and/or CK19/P-cadherin ratio(s) may be a simple and accurate prognostic indicator of clinical outcome in early-stage adenocarcinoma of the lung. If further validation studies from large patient cohorts confirm the results, adjuvant therapy could be targeted to this high-risk group.
Authors: Gavin J Gordon; Roderick V Jensen; Li-Li Hsiao; Steven R Gullans; Joshua E Blumenstock; Sridhar Ramaswamy; William G Richards; David J Sugarbaker; Raphael Bueno Journal: Cancer Res Date: 2002-09-01 Impact factor: 12.701
Authors: Anil Potti; Sayan Mukherjee; Rebecca Petersen; Holly K Dressman; Andrea Bild; Jason Koontz; Robert Kratzke; Mark A Watson; Michael Kelley; Geoffrey S Ginsburg; Mike West; David H Harpole; Joseph R Nevins Journal: N Engl J Med Date: 2006-08-10 Impact factor: 91.245
Authors: Dennis A Wigle; Igor Jurisica; Niki Radulovich; Melania Pintilie; Janet Rossant; Ni Liu; Chao Lu; James Woodgett; Isolde Seiden; Michael Johnston; Shaf Keshavjee; Gail Darling; Timothy Winton; Bobby-Joe Breitkreutz; Paul Jorgenson; Mike Tyers; Frances A Shepherd; Ming Sound Tsao Journal: Cancer Res Date: 2002-06-01 Impact factor: 12.701
Authors: A Bhattacharjee; W G Richards; J Staunton; C Li; S Monti; P Vasa; C Ladd; J Beheshti; R Bueno; M Gillette; M Loda; G Weber; E J Mark; E S Lander; W Wong; B E Johnson; T R Golub; D J Sugarbaker; M Meyerson Journal: Proc Natl Acad Sci U S A Date: 2001-11-13 Impact factor: 11.205
Authors: M E Garber; O G Troyanskaya; K Schluens; S Petersen; Z Thaesler; M Pacyna-Gengelbach; M van de Rijn; G D Rosen; C M Perou; R I Whyte; R B Altman; P O Brown; D Botstein; I Petersen Journal: Proc Natl Acad Sci U S A Date: 2001-11-13 Impact factor: 11.205
Authors: Junichi Okamoto; Johannes R Kratz; Tomomi Hirata; Iwao Mikami; Dan Raz; Mark Segal; Zhao Chen; Hai-Meng Zhou; Patrick Pham; Hui Li; Adam Yagui-Beltran; Adam Beltran; M Roshni Ray; Kiyoshi Koizumi; Kazuo Shimizu; David Jablons; Biao He Journal: Clin Lung Cancer Date: 2011-04-24 Impact factor: 4.785
Authors: J Shrout; M Yousefzadeh; A Dodd; K Kirven; C Blum; A Graham; K Benjamin; R Hoda; M Krishna; M Romano; M Wallace; E Garrett-Mayer; M Mitas Journal: Br J Cancer Date: 2008-05-27 Impact factor: 7.640