Predicting of PIK3CA Mutations for The Efficacy and Prognosis of Hepatocellular Carcinoma Patients Received Surgical Resection_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHAOCheng-mao ¹ , JINGuo-quan ² , SHANGChun-xiang ¹

1. Internal Medicine-Oncology, The Fifth People's Hospital of Qinghai Province, Xining 810007, Qinghai Province, China;
2. Department of Tumor Surgery, The Fifth People's Hospital of Qinghai Province, Xining 810007, Qinghai Province, China;

Corresponding author：

ZHAOCheng-mao, Email: zhaochengmaoqh@126.com

Keywords：

Hepatocellular carcinoma; PIK3CA gene mutation; Efficacy; Prognosis

DOI：

10.7507/1007-9424.20150307

Video：

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Objective To investigate the predicting effect of PIK3CA mutations for the efficacy and prognosis of hepatocellular carcinoma (HCC) patients received surgical resection. Methods PCR and DNA sequencing were used to detect the PIK3CA mutation status of 79 HCC tissues, its impact on the short and long term effects of the patients were analyzed. Results In this group of patients, mutation rate of PIK3CA gene exon 9 was 39.24% (31/79), PIK3CA mutation rate correlated with lymph node status and tumor differentiation (P < 0.05). The therapeutic effect of patients with PIK3CA mutation was significantly poor than that of the non-mutated group (P < 0.05). The three-year cumulative survival of patients with PIK3CA mutation (33.33%) was significantly lower than non-mutated group's (60.00%) by Kaplan-Meier (P < 0.05). Conclusion PIK3CA gene mutation in exon 9 could impact the efficiency of surgical resection in patients with HCC and could predict a poor survival prognosis.

Citation： ZHAOCheng-mao, JINGuo-quan, SHANGChun-xiang. Predicting of PIK3CA Mutations for The Efficacy and Prognosis of Hepatocellular Carcinoma Patients Received Surgical Resection. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(10): 1179-1182. doi: 10.7507/1007-9424.20150307 Copy

1.	Rudd ML, Price JC, Fogoros S, et al. A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas. Clin Cancer Res, 2011, 17(6):1331-1340.
2.	Miron A, Varadi M, Carrasco D, et al. PIK3CA mutations in in situ and invasive breast carcinomas. Cancer Res, 2010, 70(14):5674-5678.
3.	Barbareschi M, Buttitta F, Felicioni L, et al. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res, 2007, 13(20):6064-6269.
4.	王平,耿小平,朱立新, 等. 肝细胞肝癌中外周血浆DNA基因甲基化检测及意义. 中国普外基础与临床杂志, 2012, 19(7):727-732.
5.	Murugan AK, Hong NT, Fukui Y, et al. Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas. Int J Oncol, 2008, 32(1):101-111.
6.	Lee JW, Soung YH, Kim SY, et al. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene, 2005, 24(8):1477-1480.
7.	Dunlap J, Le C, Shukla A, et al. Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma. Breast Cancer Res Treat, 2010, 120(2):409-418.
8.	Li H, Zhu R, Wang L, et al. PIK3CA mutations mostly begin to develop in uctal carcinoma of the breast. Exp Mol Pathol, 2010, 88(1):150-155.
9.	MacConaill LE, Campbell CD, Kehoe SM, et al. Profiling critical cancer gene mutations in clinical tumor samples. PLoS One, 2009, 4(11):e7887.
10.	Fumagalli D, Gavin PG, Taniyama Y, et al. A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes. BMC Cancer, 2010, 10:101.
11.	Kalinsky K, Jacks LM, Heguy A, et al. PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res, 2009, 15(16):5049-5059.
12.	Campbell IG, Russell SE, Choong DY, et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res, 2004, 64(21):7678-7681.
13.	Hayes MP, Douglas W, Ellenson LH. Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma. Gynecol Oncol, 2009, 113(3):370-373.
14.	Catasus L, Gallardo A, Cuatrecasas M, et al. Concomitant PI3KAKT and p53 alterations in endometrial carcinomas are associated with poor prognosis. Mod Pathol, 2009, 22(4):522-529.
15.	Oda K, Okada J, Timmerman L, et al. PIK3CA cooperates with other phosphatidylinositol 3'-kinase pathway mutations to effect oncogenic transformation. Cancer Res, 2008, 68(19):8127-8136.
16.	Dutt A, Salvesen HB, Chen TH, et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci U S A, 2008, 105(25):8713-8717.
17.	Mandelker D, Gabelli SB, Schmidt-Kittler O, et al. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A, 2009, 106(40):16996-17001.
18.	Kang S, Bader AG, Vogt PK. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A, 2005, 102(3):802-807.
19.	Gymnopoulos M, Elsliger MA, Vogt PK. Rare cancer-specific mutations in PIK3CA show gain of function. Proc Natl Acad Sci U S A, 2007, 104(13):5569-5574.
20.	Shoji K, Oda K, Nakagawa S, et al. The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. Br J Cancer, 2009, 101(1):145-148.

1. Rudd ML, Price JC, Fogoros S, et al. A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas. Clin Cancer Res, 2011, 17(6):1331-1340.
2. Miron A, Varadi M, Carrasco D, et al. PIK3CA mutations in in situ and invasive breast carcinomas. Cancer Res, 2010, 70(14):5674-5678.
3. Barbareschi M, Buttitta F, Felicioni L, et al. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res, 2007, 13(20):6064-6269.
4. 王平,耿小平,朱立新, 等. 肝细胞肝癌中外周血浆DNA基因甲基化检测及意义. 中国普外基础与临床杂志, 2012, 19(7):727-732.
5. Murugan AK, Hong NT, Fukui Y, et al. Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas. Int J Oncol, 2008, 32(1):101-111.
6. Lee JW, Soung YH, Kim SY, et al. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene, 2005, 24(8):1477-1480.
7. Dunlap J, Le C, Shukla A, et al. Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma. Breast Cancer Res Treat, 2010, 120(2):409-418.
8. Li H, Zhu R, Wang L, et al. PIK3CA mutations mostly begin to develop in uctal carcinoma of the breast. Exp Mol Pathol, 2010, 88(1):150-155.
9. MacConaill LE, Campbell CD, Kehoe SM, et al. Profiling critical cancer gene mutations in clinical tumor samples. PLoS One, 2009, 4(11):e7887.
10. Fumagalli D, Gavin PG, Taniyama Y, et al. A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes. BMC Cancer, 2010, 10:101.
11. Kalinsky K, Jacks LM, Heguy A, et al. PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res, 2009, 15(16):5049-5059.
12. Campbell IG, Russell SE, Choong DY, et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res, 2004, 64(21):7678-7681.
13. Hayes MP, Douglas W, Ellenson LH. Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma. Gynecol Oncol, 2009, 113(3):370-373.
14. Catasus L, Gallardo A, Cuatrecasas M, et al. Concomitant PI3KAKT and p53 alterations in endometrial carcinomas are associated with poor prognosis. Mod Pathol, 2009, 22(4):522-529.
15. Oda K, Okada J, Timmerman L, et al. PIK3CA cooperates with other phosphatidylinositol 3'-kinase pathway mutations to effect oncogenic transformation. Cancer Res, 2008, 68(19):8127-8136.
16. Dutt A, Salvesen HB, Chen TH, et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci U S A, 2008, 105(25):8713-8717.
17. Mandelker D, Gabelli SB, Schmidt-Kittler O, et al. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A, 2009, 106(40):16996-17001.
18. Kang S, Bader AG, Vogt PK. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A, 2005, 102(3):802-807.
19. Gymnopoulos M, Elsliger MA, Vogt PK. Rare cancer-specific mutations in PIK3CA show gain of function. Proc Natl Acad Sci U S A, 2007, 104(13):5569-5574.
20. Shoji K, Oda K, Nakagawa S, et al. The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. Br J Cancer, 2009, 101(1):145-148.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Predicting of PIK3CA Mutations for The Efficacy and Prognosis of Hepatocellular Carcinoma Patients Received Surgical Resection

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