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A GG allele of 3′-side AKT1 SNP is associated with decreased AKT1 activation and better prognosis of gastric cancer

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

v-akt Murine thymoma viral oncogene homolog (AKT) pathway is critically involved in cancer cell growth, invasion, and survival. We examined the correlation between the genetic variations in molecules of AKT pathway and clinical outcomes of gastric cancer.

Patients and methods

Six single nucleotide polymorphisms (SNPs) located in the four core genes of AKT pathway, namely the PIK3CA, PTEN, AKT1, and mTOR, were determined in 221 patients with stage T2 and T3 gastric cancer. Additionally, the activation of AKT1 in gastric cancer tissues was examined by immunostaining. The correlation between SNPs, AKT activation, and the progress of gastric cancer was analyzed after an average of 51-month follow-up.

Results

The overall recurrence and survival rate in this study group were 54.8 and 46.6 %, respectively. The recurrence rate was reduced 30.4 %, and the survival rate was increased 33.7 % in patients with GG allele of a 3′-side AKT1 SNP (rs2498804). Significantly, GG allele was associated with lower AKT1 activation in gastric cancer tissues. On the contrary, CC allele of PTEN (rs701848) was associated with the increased risk of recurrence (hazard ratio [HR] 2.06, 95 % CI 1.19–3.58) and patient death (HR 2.01, 95 % CI 1.15–3.53).

Conclusions

The genetic variants in the PI3K/PTEN/AKT especially the GG allele in 3′ side of AKT1 are closely related to clinical outcomes of gastric cancer.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81372788) for Qiaojia Huang, the Army Clinical High and New Technology Major Project (No. 2010 gxjs026) for Jianming Tan, the Medical Scientific Research Foundation of Nanjing Command (No. 11MA107) for Lie Wang, and the Natural Science Foundation of China Grant (No. 81070272) for Feng Zheng.

Conflict of interest

No potential conflict of interests were declared.

Author information

Author notes

  1. Youdong Lin

    Present address: Department of Clinical Laboratory Medicine, Fujian Provincial Hospital, 134 Dongjie Road, Fuzhou, 350001, Fujian, China

Authors and Affiliations

  1. Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), Clinical College of Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China

    Xiaoting Wang, Youdong Lin, Fenghua Lan, Qiaojia Huang & Jianming Tan

  2. Department of Oncology, Fuzhou General Hospital (Dongfang Hospital), Clinical College of Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China

    Xuenong Ouyang

  3. Department of Pathology, Fuzhou General Hospital (Dongfang Hospital), Clinical College of Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China

    Yinghao Yu & Xuzhou Wang

  4. Department of General Surgery, Fuzhou General Hospital (Dongfang Hospital), Clinical College of Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China

    Lie Wang

  5. Organ Transplant Institute, Fuzhou General Hospital (Dongfang Hospital), Clinical College of Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China

    Jianming Tan

  6. Department of Nephrology and Central Laboratory, Fuzhou General Hospital (Dongfang Hospital), Clinical College of Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China

    Feng Zheng

Authors
  1. Xiaoting Wang
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  2. Youdong Lin
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  3. Fenghua Lan
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  4. Yinghao Yu
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  7. Qiaojia Huang
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  8. Lie Wang
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  9. Jianming Tan
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  10. Feng Zheng
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Corresponding authors

Correspondence to Qiaojia Huang, Lie Wang, Jianming Tan or Feng Zheng.

Additional information

Xiaoting Wang and Youdong Lin are contributed equally to this paper.

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Wang, X., Lin, Y., Lan, F. et al. A GG allele of 3′-side AKT1 SNP is associated with decreased AKT1 activation and better prognosis of gastric cancer. J Cancer Res Clin Oncol 140, 1399–1411 (2014). https://doi.org/10.1007/s00432-014-1663-x

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  • DOI: https://doi.org/10.1007/s00432-014-1663-x

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