Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Eukaryotic Gene Expression
IF: 2.156 5-Year IF: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.2020028658
pages 299-309

Clinical Association between Phospho-AKT Expression with Clinicopathological Characteristics of Gastrointestinal Cancer Patients: A Meta-Analysis

Hossein Abdeahad
Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA
Afsane Bahrami
Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
Majid Khazaei
Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Gordon A. Ferns
Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, BN1 9PH, UK
Marjan Erfani
Department of Neurology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
Hamid Fiuji
Department of Biochemistry, Payame Noor University, Mashhad, Iran
Mehran Pahirzad
Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Amir Avan
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Seyed Mahdi Hassanian Mehr
Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

ABSTRACT

Deregulation of AKT (protein kinase B) is frequently observed in human malignancies including gastrointestinal (GI) cancers. Here we have reviewed the association between AKT phosphorylation (activation) and clinical and pathological characteristics of patients with GI cancer. Articles in the EMBASE, PubMed, Cochrane Library, and Web of Science databases were searched up to July 2018. Eighteen studies comprising 1,698 patients with 5 different cancer types were included in the meta-analysis. In the pooled analysis, AKT phosphorylation was positively correlated with tumor size (r = 0.14, 95% CI: 0.06-0.22; P < 0.001), tumor grade (r = 0.08, 95% CI: 0.02-0.14; P < 0.009), tumor stage (r = 0.19, 95% CI: 0.13-0.24; P < 0.001), lymph node status (r = 0.18, 95% CI: 0.09-0.25; P < 0.001) and the presence of distant metastasis (r = 0.14, 95% CI: 0.06-0.22; P < 0.001) in the patients with GI cancer. These findings support the potential clinical value of AKT as a prognostic marker and therapeutic target in patients with GI carcinomas.

REFERENCES

  1. Bahrami A, Shahidsales S, Khazaei M, Ghayour-Mobarhan M, Maftouh M, Hassanian SM, Avan A. C-Met as a potential target for the treatment of gastrointestinal cancer: Current status and future perspectives. J Cell Physiol. 2017;232(10):2657-73.

  2. Datta SR, Brunet A, Greenberg ME. Cellular survival: A play in three Akts. Genes Dev. 1999;13(22):2905-27.

  3. Staal SP. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: Amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A. 1987;84(14):5034-7.

  4. Coffer PJ, Jing J, Woodgett JR. Protein kinase B (c-Akt): A multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J. 1998;335(1):1-13.

  5. Nakatani K, Thompson DA, Barthel A, Sakaue H, Liu W, Weigel RJ, Roth RA. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgenindependent prostate cancer lines. J Biol Chem. 1999; 274(31):21528-32.

  6. Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S, Uhlik M, Lin A, Du J, Qian YW, Zeckner DJ, Tucker-Kellogg G, Touchman J, Patel K, Mousses S, Bittner M, Schevitz R, Lai MH, Blanchard KL, Thomas JE. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature. 2007;448(7152):439-44.

  7. Bahrami A, Khazaei M, Hasanzadeh M, ShahidSales S, Joudi Mashhad M, Farazestanian M, Sadeghnia HR, Rezayi M, Maftouh M, Hassanian SM, Avan A. Therapeutic potential of targeting PI3K/AKT pathway in treatment of colorectal cancer: Rational and progress. J Cell Biochem. 2018;119(3):2460-9.

  8. Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002;14(5):381-95.

  9. Scheid MP, Woodgett JR. PKB/AKT: Functional insights from genetic models. Nature Rev Mol Cell Biol. 2001;2(10):760-8.

  10. Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, Van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 2003;63(9):2172-8.

  11. Li H-F, Kim J-S, Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat Oncol. 2009;4(1):43.

  12. Bahrami A, Khazaei M, Shahidsales S, Hassanian SM, Hasanzadeh M, Maftouh M, Ferns GA, Avan A. The therapeutic potential of PI3K/Akt/mTOR inhibitors in breast cancer: Rational and progress. J Cell Biochem. 2018;119(1):213-22.

  13. Higgins J, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-58.

  14. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719-48.

  15. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-88.

  16. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-34.

  17. Borenstein M, Hedges L, Higgins J, Rothstein H. Comprehensive meta-analysis version 2. Englewood, NJ: Biostat; 2005. p. 104.

  18. Yang Z-Z, Tschopp O, Baudry A, Dummler B, Hynx D, Hemmings BA. Physiological functions of protein kinase B/Akt. Biochem Soc Trans. 2004;32(Pt 2):350-4.

  19. Chang F, Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, Franklin RA, McCubrey JA. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: A target for cancer chemo-therapy. Leukemia. 2003;17(3):590-603.

  20. Bahrami A, Hasanzadeh M, Hassanian SM, ShahidSales S, Mobarhan MG, Ferns GA, Avan A. The potential value of the PI3K/Akt/mTOR signaling pathway for assessing prognosis in cervical cancer and as a target for therapy. J Cell Biochem. 2017;118(12):4163-9.

  21. Itoh N, Semba S, Ito M, Takeda H, Kawata S, Yamakawa M. Phosphorylation of Akt/PKB is required for suppression of cancer cell apoptosis and tumor progression in human colorectal carcinoma. Cancer. 2002;94(12):3127-34.

  22. Lugli A, Zlobec I, Minoo P, Baker K, Tornillo L, Terracciano L, Jass JR. Role of the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT pathways downstream molecules, phosphorylated extracellular signal-regulated kinase, and phosphorylated AKT in colorectal cancer-a tissue microarray-based approach. Hum Pathol. 2006;37(8):1022-31.

  23. Malinowsky K, Nitsche U, Janssen KP, Bader FG, Spath C, Drecoll E, Keller G, Hofler H, Slotta-Huspenina J, Becker KF. Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer. British J Cancer. 2014 Apr;110(8):2081-9.

  24. Henderson-Jackson EB, Helm J, Ghayouri M, Hakam A, Nasir A, Leon M, Bui M, Yeatman T, Coppola D. Correlation between Mcl-1 and pAKT protein expression in colorectal cancer. Int J Clin Exper Pathol. 2010; 3(8):768.

  25. Schmitz KJ, Wohlschlaeger J, Alakus H, Bohr J, Stauder MA, Worm K, Winde G, Schmid KW, Baba HA. Activation of extracellular regulated kinases (ERK1/2) but not AKT predicts poor prognosis in colorectal carcinoma and is associated with k-ras mutations. Virchows Archiv. 2007 Feb 1;450(2):151-9.

  26. Saglam O, Garrett CR, Boulware D, Sayegh Z, Shibata D, Malafa M, Yeatman T, Cheng JQ, Sebti S, Coppola D. Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia. Clin Colorectal Cancer. 2007 Sep 1;6(9):652-6.

  27. Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, Karakayali H, Haberal M. Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence? Am J Surgery. 2008 Jun 1;195(6):719-25.

  28. Zhang Y, Liu X, Zhang J, Li L, Liu C. The expression and clinical significance of PI3K, pAkt and VEGF in colon cancer. Oncol Lett. 2012;4:763-766.

  29. Cinti C, Vindigni C, Zamparelli A, La Sala D, Epistolato MC, Marrelli D, Cevenini G, Tosi P. Activated Akt as an indicator of prognosis in gastric cancer. Virchows Archiv. 2008 Nov 1;453(5):449-55.

  30. Ying J, Xu Q, Liu B, Zhang G, Chen L, Pan H. The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis. OncoTargets Ther. 2015;8:2427.

  31. Chen JS, Wang Q, Fu XH, Huang XH, Chen XL, Cao LQ, Chen LZ, Tan HX, Li W, Bi J, Zhang LJ. Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9. Hepatol Res. 2009 Feb;39(2):177-86.

  32. Schmitz KJ, Wohlschlaeger J, Lang H, Sotiropoulos GC, Malago M, Steveling K, Reis H, Cicinnati VR, Schmid KW, Baba HA. Activation of the ERK and AKT signalling pathway predicts poor prognosis in hepatocellular carcinoma and ERK activation in cancer tissue is associated with hepatitis C virus infection. J Hepatol. 2008 Jan 1;48(1):83-90.

  33. Tang Y, Wang R, Zhang Y, Lin S, Qiao N, Sun Z, Cheng S, Zhou W. Co-Upregulation of 14-3-3Z and P-Akt is associated with oncogenesis and recurrence of hepatocellular carcinoma. Cellular Physiol Biochem. 2018;45(3): 1097-107.

  34. Pontes HA, Pontes FS, de Jesus AS, Soares MC, Gon?alves FL, de Lucena Botelho T, do Carmo Ribeiro J, dos Santos Pinto Jr D. p-A kt and its relationship with clinicopathological features and survival in oral squamous cell carcinoma: an immunohistochemical study. J Oral Pathol Med. 2015 Aug;44(7):532-7.

  35. Lyu J, Song H, Tian Z, Miao Y, Ren G, Guo W. Predictive value of pAKT/PTEN expression in oral squamous cell carcinoma treated with cetuximab-based chemotherapy. Oral Surg, Oral Med, Oral Pathol Oral Radiol. 2016;121:67-72.

  36. Zhao J, Wang S, Liu N, Tang X. Correlation between the expression of Id-1 and hyperthermia-associated molecules in oral squamous cell carcinoma. J Clin Pathol. 2013 Sep 1;66(9):758-63.

  37. Liu J, Sun SH, Sun SJ, Huang C, Hu HH, Jin YB, Qiu ZJ. Phosph-Akt1 expression is associated with a favourable prognosis in pancreatic cancer. Annals Acad Med Singapore. 2010 Jul 1;39(7):548.

  38. Xia S, Feng Z, Qi X, Yin Y, Jin J, Wu Y, Wu H, Feng Y, Tao M. Clinical implication of Sox9 and activated Akt expression in pancreatic ductal adenocarcinoma. Med Oncol. 2015 Jan 1;32(1):358.

  39. Xiaoping L, Xiaowei Z, Leizhen Z, Weijian G. Expression and significance of CD44 and p-AKT in pancreatic head cancer. World J Surg Oncol. 2015;13:334.

  40. Ozaki-Ohgami Y, Iwamoto A, Yoshioka S, Tatebe S, Hirooka Y, Ikeguchi M. Expression of phospho-Akt and PTEN proteins predicts the survival of patients with pancreatic cancer. Yonago Acta Medica. 2006;49:9.


Articles with similar content:

Association between ABCB1 G2677T/A Polymorphism and Breast Cancer Risk: A Meta-Analysis
Critical Reviews™ in Eukaryotic Gene Expression, Vol.29, 2019, issue 3
Kangke Shi, Zhihao Wei, Hongchao Liu, Yu Zhang
MTHFR-C677T Gene Polymorphism and Susceptibility to Acute Lymphoblastic Leukemia in Children: A Meta-Analysis
Critical Reviews™ in Eukaryotic Gene Expression, Vol.30, 2020, issue 2
Zhi-Yong Ke, Yu-Xin Pei, Li-Na Wang, Xue-Qun Luo, Yan-Lai Tang, Cong Liang, Li-Bin Huang, Yu Li, Xiao-Li Zhang
The Prognostic Value of Small Noncoding microRNA-21 Expression in the Survival of Cancer Patients: A Meta-Analysis
Critical Reviews™ in Eukaryotic Gene Expression, Vol.30, 2020, issue 3
Gordon A. Ferns, Seyed Mahdi Hassanian Mehr, Maryam Moradi Binabaj, Mikhail Ryzhikov, Amir Avan, Saman Soleimanpour, Majid Khazaei, Afsane Bahrami
TCF7L2 rs12255372 (G > T) Polymorphism Contributes to Breast Carcinogenesis: Evidence from a Meta-Analysis
Critical Reviews™ in Eukaryotic Gene Expression, Vol.23, 2013, issue 4
Qun Zhang, Zexing Wang, Weiwei Nie, Fengxia Chen, Bin Yang, Yanru Wang, Xiaoxiang Guan
XRCC1 Arg194Trp and Arg280His Polymorphisms in Bladder Cancer Susceptibility: A Meta-Analysis
Critical Reviews™ in Eukaryotic Gene Expression, Vol.23, 2013, issue 4
Guangjun Jiao, Qinghua Yin, Lian Li, Chuan Liu, Yajie Wang, Mei Wang