Phosphorylated AMP-activated protein kinase expression associated with prognosis for patients with gastric cancer treated with cisplatin-based adjuvant chemotherapy
- 372 Downloads
The present study analyzed the expression of phosphorylated AMP-activated protein kinase (pAMPK), Fyn kinase, and pyruvate dehydrogenase kinase-1 (PDK-1) and their impact on the survival of patients with resected gastric cancer who received cisplatin-based adjuvant chemotherapy.
Patients and methods
Korean patients with stage II–IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection and received a combination regimen of cisplatin and S-1 were enrolled. Immunohistochemistry was carried out to determine the expression of pAMPK, Fyn kinase, and PDK-1 in operative specimens of gastric cancer. The expression was divided into two groups according to the intensity score (negative: 0 or 1+ and positive: 2+ or 3+).
From January 2006 to July 2010, 73 tumor samples obtained from 74 patients were analyzed. Forty patients were included in the pAMPK-positive group, while 33 patients were included in the pAMPK-negative group. Meanwhile, positive Fyn kinase expression was observed in only 10 patients (13.7 %), and there was no or very weak PDK-1 staining. The clinicopathologic characteristics were similar between the two groups according to the expression of pAMPK. With a median follow-up duration of 26.5 months (2.6–73.2), the estimated 3-year relapse-free survival (RFS) and overall survival rates were 55.0 and 78.4 %, respectively. In a multivariate analysis adjusted for age, sex, Lauren classification, and stage, the pAMPK-negative group was significantly associated with improved RFS (Hazard ratio = 0.459, 95 % CI 0.109–0.711, P = 0.043).
A low expression of pAMPK was found to be correlated with better RFS in patients with resected gastric cancer treated with adjuvant cisplatin-based chemotherapy.
KeywordsAMP-activated protein kinase Gastric cancer Cisplatin Adjuvant chemotherapy Prognosis
- 3.Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y (2011) Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol 29(33):4387–4393PubMedCrossRefGoogle Scholar
- 11.Buckendahl AC, Budczies J, Fiehn O, Darb-Esfahani S, Kind T, Noske A, Weichert W, Sehouli J, Braicu E, Dietel M, Denkert C (2011) Prognostic impact of AMP-activated protein kinase expression in ovarian carcinoma: correlation of protein expression and GC/TOF-MS-based metabolomics. Oncol Rep 25(4):1005–1012PubMedGoogle Scholar
- 13.Park HU, Suy S, Danner M, Dailey V, Zhang Y, Li H, Hyduke DR, Collins BT, Gagnon G, Kallakury B, Kumar D, Brown ML, Fornace A, Dritschilo A, Collins SP (2009) AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther 8(4):733–741PubMedCrossRefGoogle Scholar
- 18.Kang BW, Kim JG, Chae YS, Lee YJ, Lee SJ, Moon JH, Sohn SK, Jung MK, Jeon SW, Jang YJ, Seo J, Lee YH, Kwon O, Chung HY, Yu W (2012) Pilot study of adjuvant chemotherapy with 3-week combination of S-1 and cisplatin for patients with stage II-IV (M0) gastric cancer. Invest New Drugs 30(4):1671–1675PubMedCrossRefGoogle Scholar
- 23.Baba Y, Nosho K, Shima K, Meyerhardt JA, Chan AT, Engelman JA, Cantley LC, Loda M, Giovannucci E, Fuchs CS, Ogino S (2010) Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer. Br J Cancer 103(7):1025–1033PubMedCrossRefGoogle Scholar
- 24.Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC (2006) DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355(10):983–991PubMedCrossRefGoogle Scholar