This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, J. Articles by Mao, L. Search for Related Content PubMed PubMed Citation Articles by Wang, J. Articles by Mao, L.

Value of p16^INK4a and RASSF1A Promoter Hypermethylation in Prognosis of Patients with Resectable Non–Small Cell Lung Cancer

¹ Department of Thoracic/Head and Neck Medical Oncology, and the ² Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and ³ Department of Oncology, Beijing University School of Oncology, Beijing Cancer Hospital, Beijing Institution of Cancer Research, Beijing, China

The p16^INK4a and RASSF1A are tumor suppressor genes frequently inactivated by de novo promoter hypermethylation in non-small cell lung cancer. We studied 119 patients with non-small cell lung cancer (70 stage I/II and 49 stage IIIA) who had undergone surgery with curative intent. The p16^INK4a and RASSF1A promoter methylation statuses were determined by methylation-specific PCR. Statistical analyses, all two-sided, were performed to determine the prognostic effect of hypermethylation on various clinical parameters. Hypermethylation of the p16^INK4a and RASSF1A promoters was found in 58 (49%) and 46 (39%) tumors, respectively, and 30 tumors (25%) exhibited hypermethylation of both gene promoters. In patients with stage I/II tumors, only p16^INK4a promoter hypermethylation was associated with a poor 5-year overall survival rate (P = 0.002). In patients with stage IIIA disease, however, RASSF1A promoter hypermethylation was a stronger predictor of a poor 5-year overall survival rate (P < 0.0001) than p16^INK4a promoter hypermethylation. Among the 49 patients with stage IIIA tumors, 16 (89%) of the 18 patients whose tumors showed RASSF1A promoter hypermethylation died within 3 years after surgery, as compared with only 12 (39%) of the 31 patients whose tumors had no RASSF1A promoter hypermethylation (P < 0.0001). Multivariate analysis indicated that RASSF1A promoter hypermethylation was the stronger independent predictor for survival in patients with locally advanced non-small cell lung cancer. Our results indicate that p16^INK4a promoter hypermethylation predicts a poor 5-year survival rates for patients with resectable non-small cell lung cancer, particularly for those with early stage tumors, whereas RASSF1A promoter hypermethylation is a profound prognostic predictor for patients with locally advanced non-small cell lung cancer, suggesting an important role of RASSF1A in non-small cell lung cancer progression.

This article has been cited by other articles:

				K. Amara, M. Trimeche, S. Ziadi, A. Laatiri, M. Hachana, and S. Korbi Prognostic significance of aberrant promoter hypermethylation of CpG islands in patients with diffuse large B-cell lymphomas Ann. Onc., October 1, 2008; 19(10): 1774 - 1786. [Abstract] [Full Text] [PDF]

				M. V. Brock, C. M. Hooker, E. Ota-Machida, Y. Han, M. Guo, S. Ames, S. Glockner, S. Piantadosi, E. Gabrielson, G. Pridham, et al. DNA Methylation Markers and Early Recurrence in Stage I Lung Cancer N. Engl. J. Med., March 13, 2008; 358(11): 1118 - 1128. [Abstract] [Full Text] [PDF]

				J. Gu, D. Berman, C. Lu, I. I. Wistuba, J. A. Roth, M. Frazier, M. R. Spitz, and X. Wu Aberrant Promoter Methylation Profile and Association with Survival in Patients with Non-Small Cell Lung Cancer Clin. Cancer Res., December 15, 2006; 12(24): 7329 - 7338. [Abstract] [Full Text] [PDF]

				X. Cui, T. Wakai, Y. Shirai, K. Hatakeyama, and S. Hirano Chronic Oral Exposure to Inorganic Arsenate Interferes with Methylation Status of p16INK4a and RASSF1A and Induces Lung Cancer in A/J Mice Toxicol. Sci., June 1, 2006; 91(2): 372 - 381. [Abstract] [Full Text] [PDF]

				Y. T. Kim, S. J. Park, S. H. Lee, H. J. Kang, S. Hahn, C. H. Kang, S. W. Sung, and J. H. Kim Prognostic implication of aberrant promoter hypermethylation of CpG islands in adenocarcinoma of the lung J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1378 - 1378. [Abstract] [Full Text] [PDF]

				L. van der Weyden, K. K. Tachibana, M. A. Gonzalez, D. J. Adams, B. L. Ng, R. Petty, A. R. Venkitaraman, M. J. Arends, and A. Bradley The RASSF1A Isoform of RASSF1 Promotes Microtubule Stability and Suppresses Tumorigenesis Mol. Cell. Biol., September 15, 2005; 25(18): 8356 - 8367. [Abstract] [Full Text] [PDF]

				A. Agathanggelou, W. N. Cooper, and F. Latif Role of the Ras-Association Domain Family 1 Tumor Suppressor Gene in Human Cancers Cancer Res., May 1, 2005; 65(9): 3497 - 3508. [Abstract] [Full Text] [PDF]