Phosphatidylinositol 3-kinase could be a promising target in lung cancer therapy.
作者： Qun Ju , Haofei Wang , Wujun Wang , Kaican Cai , Hua Wu
DOI:
关键词:
摘要: Summary Purpose: To investigate the prevalence of phosphatidylinositol 3-kinase (PIK3CA) gene amplification in lung cancer, and to explore its prognostic value. Methods: A total 647 tumor samples from 290 patients were included study. The ratio PIK3CA signals/centromere 3 signals cancer cells was estimated by fluorescence situ hybridization (FISH) analysis. Results: Both gains amplifications significantly more frequent squamous cell (gains: 19.4%; amplifications: 34.1%; p<0.0001) large carcinoma 22.4%; 20.4%; compared with adenocarcinomas (gains 3.0%; 4.0%). Conversely, displayed deletions locus than other two histologic types (p<0.0001). No clear correlation between status pT stage, pN stage or degree differentiation found. Ki67 increased increasing copy number: 47 tumors a deletion had mean 16, while 103 showed 28 (p=0.004). Significant association proliferation PIK 3CA found (p<0.05). However, no significant seen patient survival amplifications, gains. Conclusion: carcinomas higher adenocarcinomas. results suggest that could be promising target for selective therapy.
参考文章(26)
Do-Sun Byun, Kyucheol Cho, Byung-Kyu Ryu, Min-Goo Lee, Jae-Il Park, Kwon-Seok Chae, Hyo-Jong Kim, Sung-Gil Chi, Frequent monoallelic deletion of PTEN and its reciprocal associatioin with PIK3CA amplification in gastric carcinoma. International Journal of Cancer. ,vol. 104, pp. 318- 327 ,(2003) , 10.1002/IJC.10962
Mark D. Iannettoni, Mark B. Orringer, Matthew Schipper, Lin Lin, Charles T. Miller, David G. Beer, Daniel Normolle, Justin R. Moy, Dean E. Brenner, Gene amplification in esophageal adenocarcinomas and Barrett's with high-grade dysplasia. Clinical Cancer Research. ,vol. 9, pp. 4819- 4825 ,(2003)
Guojun Wu, Mingzhao Xing, Elizabeth Mambo, Xin Huang, Junwei Liu, Zhongmin Guo, Aditi Chatterjee, David Goldenberg, Susanne M Gollin, Saraswati Sukumar, Barry Trink, David Sidransky, Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Research. ,vol. 7, pp. 1- 8 ,(2005) , 10.1186/BCR1262
Stefano Volinia, Ian Hiles, Elizabeth Ormondroyd, Dean Nizetic, Rachele Antonacci, Mariano Rocchi, Michael O. Waterfield, Molecular Cloning, cDNA Sequence, and Chromosomal Localization of the Human Phosphatidylinositol 3-Kinase p110α (PIK3CA) Gene Genomics. ,vol. 24, pp. 472- 477 ,(1994) , 10.1006/GENO.1994.1655
Pixu Liu, Hailing Cheng, Thomas M. Roberts, Jean J. Zhao, Targeting the phosphoinositide 3-kinase pathway in cancer Nature Reviews Drug Discovery. ,vol. 8, pp. 627- 644 ,(2009) , 10.1038/NRD2926
Brendan D. Manning, Lewis C. Cantley, AKT/PKB signaling: navigating downstream. Cell. ,vol. 129, pp. 1261- 1274 ,(2007) , 10.1016/J.CELL.2007.06.009
Koji Okudela, Masaya Suzuki, Shinji Kageyama, Tomoyasu Bunai, Kiyoko Nagura, Hisaki Igarashi, Kazuya Takamochi, Kazuya Suzuki, Takeshi Yamada, Hiroshi Niwa, Riuko Ohashi, Hiroshi Ogawa, Hiroki Mori, Hitoshi Kitamura, Takeshi Kaneko, Toshihiro Tsuneyoshi, Haruhiko Sugimura, PIK3CA mutation and amplification in human lung cancer. Pathology International. ,vol. 57, pp. 664- 671 ,(2007) , 10.1111/J.1440-1827.2007.02155.X
I Petersen, H Langreck, G Wolf, A Schwendel, R Psille, P Vogt, MB Reichel, T Ried, M Dietel, Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p British Journal of Cancer. ,vol. 75, pp. 79- 86 ,(1997) , 10.1038/BJC.1997.13
Guang Jin, Min Jung Kim, Hyo-Sung Jeon, Jin Eun Choi, Dong Sun Kim, Eung Bae Lee, Sung Ick Cha, Ghil Sook Yoon, Chang Ho Kim, Tae Hoon Jung, Jae Yong Park, PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers Lung Cancer. ,vol. 69, pp. 279- 283 ,(2010) , 10.1016/J.LUNGCAN.2009.11.012
Binaifer R Balsara, Joseph R Testa, Chromosomal imbalances in human lung cancer. Oncogene. ,vol. 21, pp. 6877- 6883 ,(2002) , 10.1038/SJ.ONC.1205836