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Author:

Su, Rujuan (Su, Rujuan.) | Nan, Haocheng (Nan, Haocheng.) | Guo, Hui (Guo, Hui.) | Ruan, Zhiping (Ruan, Zhiping.) | Jiang, Lili (Jiang, Lili.) | Song, Yuanyuan (Song, Yuanyuan.) | Nan, Kejun (Nan, Kejun.)

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SCIE PubMed

Abstract:

Aim: We aimed to investigate the associations between components of the phosphatase and tensin homolog deleted on chromosome 10/protein kinase B/mammalian target of rapamycin (PTEN/AKT/mTOR) pathway and liver cancer stem cell (LCSC) markers, including CD133, CD90, CD44, and epithelial cell adhesion molecule (EpCAM), and to further evaluate the predictive values of these biomarkers for recurrence and survival in hepatocellular carcinoma (HCC). Method: Protein expressions and mRNA levels of PTEN and LCSC markers were determined in 110 HCC tissues and 98 adjacent non-tumor tissues. Protein expressions of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) were detected to evaluate the activation of the PTEN/AKT/mTOR pathway by using immunohistochemistry. Prognostic significance was analyzed by univariate and multivariate analysis. Results: Loss of PTEN expression was negatively correlated with positive expression of CD133, CD90, and EpCAM (P< 0.05). Positive expression of p-AKT and p-mTOR were positively associated with positive expression for CD133, CD90, and EpCAM (P< 0.05). By univariate and multivariate analysis, a higher level of a-fetoprotein, loss of PTEN expression, and CD133-positive, p-AKT-positive, p-mTOR-positive, and EpCAM-positive signals were predictors for HCC recurrence, whereas advanced TNM stage, loss of PTEN expression, and positive expression of p-AKT, p-mTOR, and CD133 were predictors for survival. Patients with PTEN-/CD133(+) or PTEN-/EpCAM(+) HCC had shorter recurrence-free survival and overall survival times. Conclusion: The PTEN/AKT/mTOR pathway might play a crucial role in driving recurrence and influencing prognosis in HCC. There could be a potential repressive relationship between components of the PTEN/AKT/mTOR pathway and LCSCs. The combination of PTEN with CD133 or EpCAM expression may serve as a screening tool to monitor recurrence and predict prognosis.

Keyword:

AKT cancer stem cell hepatocellular carcinoma mammalian target of rapamycin PTEN

Author Community:

  • [ 1 ] [Su, Rujuan; Nan, Haocheng; Guo, Hui; Ruan, Zhiping; Jiang, Lili; Song, Yuanyuan; Nan, Kejun] Xi An Jiao Tong Univ, Med Coll, Affiliated Hosp 1, Dept Oncol, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China

Reprint Author's Address:

  • Xi An Jiao Tong Univ, Med Coll, Affiliated Hosp 1, Dept Oncol, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.

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Source :

HEPATOLOGY RESEARCH

ISSN: 1386-6346

Year: 2016

Issue: 13

Volume: 46

Page: 1380-1391

2 . 6 0 2

JCR@2016

4 . 2 8 8

JCR@2020

ESI Discipline: CLINICAL MEDICINE;

ESI HC Threshold:158

JCR Journal Grade:3

CAS Journal Grade:4

Cited Count:

WoS CC Cited Count: 31

SCOPUS Cited Count: 35

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 8

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