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The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis.

Ying J, Xu Q, Liu B, Zhang G, Chen L, Pan H - Onco Targets Ther (2015)

Bottom Line: The risk of death for the cases with three biomarkers negative was 0.017 times that for the cases with three biomarkers positive (P=0.022).Our study generated the hypothesis that patients with gastric cancer with simultaneous expression of PI3K/p-AKT/p-mTOR had worse outcome.But we need more rigorous validation in a larger data set.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemotherapy,Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, People's Republic of China ; Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People's Republic of China.

ABSTRACT

Objective: To analyze the correlation between sequential aspects of the phosphoinositide-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway by immunohistochemistry in the primary lesion of gastric cancer, clinicopathologic factors, and survival in Chinese patients to explore the role of sequential analysis of multiple targets in prognoses.

Methods: Immunohistochemistry was performed to examine the expression of PI3K, phosphorylated-AKT (p-AKT), and phosphorylated-mTOR (p-mTOR) in 59 primary lesion samples ranging from Stages I to IV after gastrectomy. The correlation between sequential expression of multiple targets, and clinicopathologic factors and survival was analyzed.

Results: The positive expression rates of PI3K, p-AKT, and p-mTOR were 49%, 58%, and 56%, respectively. There were eleven cases with three biomarkers positive (19%), 22 cases with two biomarkers positive (37%), and 19 cases with only one biomarker positive (32%). Seven cases (12%) were all negative. Multi-factorial Cox regression analysis showed that neural invasion, vascular invasion, size of the tumor, lymph nodes affected, metastasis, carbohydrate antigen 19-9 level, and PI3K/p-AKT/p-mTOR simultaneous expression were independent prognostic parameters. The risk of death for the cases with two biomarkers positive was 0.367 times that for the cases with three biomarkers positive (P=0.166). The risk of death for the cases with only one biomarker positive was 0.105 times that for the cases with three biomarkers positive (P=0.058). The risk of death for the cases with three biomarkers negative was 0.017 times that for the cases with three biomarkers positive (P=0.022).

Conclusion: Our study generated the hypothesis that patients with gastric cancer with simultaneous expression of PI3K/p-AKT/p-mTOR had worse outcome. But we need more rigorous validation in a larger data set.

No MeSH data available.


Related in: MedlinePlus

p-AKT-positive expression in the primary lesion (×200).Abbreviation: p-AKT, phosphorylated-AKT.
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f2-ott-8-2427: p-AKT-positive expression in the primary lesion (×200).Abbreviation: p-AKT, phosphorylated-AKT.

Mentions: The immunohistochemistry results showed that the positive rate of PI3K, p-AKT, and p-mTOR was 49%, 58%, and 56%, respectively (Figures 1–3). The correlation among the expression of PI3K, p-AKT, and p-mTOR and sex, age, anemia, differentiation, tumor diameter, alkaline phosphatase, C-reactive protein, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), TNM staging, neural invasion, vascular invasion, and performance status grading was examined. LDH levels were significantly correlated with PI3K/p-AKT/p-mTOR expression. Six patients with increased LDH levels were positively expressed for all three biomarkers. Males had higher p-mTOR-positive rate than females (66% vs 27%, P=0.008). The patients with a tumor diameter <5.0 cm had higher PI3K-positive rate (58% vs 32%, P=0.063) and p-AKT-positive rate (68% vs 37%, P=0.026). The patients with increased levels of CEA had higher PI3K-positive rate (77% vs 41%, P=0.023) and lower p-mTOR-positive rate (31% vs 63%, P=0.038). Sequential analysis of biomarkers showed no relationship with clinicopathologic factors.


The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis.

Ying J, Xu Q, Liu B, Zhang G, Chen L, Pan H - Onco Targets Ther (2015)

p-AKT-positive expression in the primary lesion (×200).Abbreviation: p-AKT, phosphorylated-AKT.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562727&req=5

f2-ott-8-2427: p-AKT-positive expression in the primary lesion (×200).Abbreviation: p-AKT, phosphorylated-AKT.
Mentions: The immunohistochemistry results showed that the positive rate of PI3K, p-AKT, and p-mTOR was 49%, 58%, and 56%, respectively (Figures 1–3). The correlation among the expression of PI3K, p-AKT, and p-mTOR and sex, age, anemia, differentiation, tumor diameter, alkaline phosphatase, C-reactive protein, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), TNM staging, neural invasion, vascular invasion, and performance status grading was examined. LDH levels were significantly correlated with PI3K/p-AKT/p-mTOR expression. Six patients with increased LDH levels were positively expressed for all three biomarkers. Males had higher p-mTOR-positive rate than females (66% vs 27%, P=0.008). The patients with a tumor diameter <5.0 cm had higher PI3K-positive rate (58% vs 32%, P=0.063) and p-AKT-positive rate (68% vs 37%, P=0.026). The patients with increased levels of CEA had higher PI3K-positive rate (77% vs 41%, P=0.023) and lower p-mTOR-positive rate (31% vs 63%, P=0.038). Sequential analysis of biomarkers showed no relationship with clinicopathologic factors.

Bottom Line: The risk of death for the cases with three biomarkers negative was 0.017 times that for the cases with three biomarkers positive (P=0.022).Our study generated the hypothesis that patients with gastric cancer with simultaneous expression of PI3K/p-AKT/p-mTOR had worse outcome.But we need more rigorous validation in a larger data set.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemotherapy,Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, People's Republic of China ; Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People's Republic of China.

ABSTRACT

Objective: To analyze the correlation between sequential aspects of the phosphoinositide-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway by immunohistochemistry in the primary lesion of gastric cancer, clinicopathologic factors, and survival in Chinese patients to explore the role of sequential analysis of multiple targets in prognoses.

Methods: Immunohistochemistry was performed to examine the expression of PI3K, phosphorylated-AKT (p-AKT), and phosphorylated-mTOR (p-mTOR) in 59 primary lesion samples ranging from Stages I to IV after gastrectomy. The correlation between sequential expression of multiple targets, and clinicopathologic factors and survival was analyzed.

Results: The positive expression rates of PI3K, p-AKT, and p-mTOR were 49%, 58%, and 56%, respectively. There were eleven cases with three biomarkers positive (19%), 22 cases with two biomarkers positive (37%), and 19 cases with only one biomarker positive (32%). Seven cases (12%) were all negative. Multi-factorial Cox regression analysis showed that neural invasion, vascular invasion, size of the tumor, lymph nodes affected, metastasis, carbohydrate antigen 19-9 level, and PI3K/p-AKT/p-mTOR simultaneous expression were independent prognostic parameters. The risk of death for the cases with two biomarkers positive was 0.367 times that for the cases with three biomarkers positive (P=0.166). The risk of death for the cases with only one biomarker positive was 0.105 times that for the cases with three biomarkers positive (P=0.058). The risk of death for the cases with three biomarkers negative was 0.017 times that for the cases with three biomarkers positive (P=0.022).

Conclusion: Our study generated the hypothesis that patients with gastric cancer with simultaneous expression of PI3K/p-AKT/p-mTOR had worse outcome. But we need more rigorous validation in a larger data set.

No MeSH data available.


Related in: MedlinePlus