Studies on the Expression Patterns of Class I PI3K Catalytic Subunits and Its Prognostic Significance in Colorectal Cancer |
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Authors: | Binbin Cui Ji Tao Yanmei Yang |
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Institution: | (1) Department of Colorectal Surgery, The Affiliated 3rd Hospital, Harbin Medical University, Harbin, People’s Republic of China;(2) Department of Medical Oncology, The Affiliated 3rd Hospital, Harbin Medical University, Harbin, People’s Republic of China;(3) Cancer Research Institute, Harbin Medical University, Harbin, 150081, People’s Republic of China; |
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Abstract: | The phosphatidylinositol 3-kinase/AKT (PI3K/AKT) pathway plays a critical role in human cancer. We determined the expression
patterns of class I PI3K catalytic subunits and evaluated their importance in the development or progression of colorectal
cancer (CRC). For this purpose, expression of class I PI3K isoforms was evaluated in 82 primary CRC and paired non-cancerous
mucosa samples by qRT-PCR. P-AKT-Ser473 and P-AKT-Thr308 expression were measured by western blot. We found that, compared
with paired non-cancerous mucosa samples, mRNA expression of p110α and p110β in CRCs was significantly increased to 2.02-fold
(95% confidence interval CI] 1.25–3.28 fold) and 1.76-fold (95% CI 1.19–2.60 fold), respectively; while slight differences
were found regarding the expression of p110δ (0.57-fold; 95% CI 0.31–1.07 fold) and p110γ (0.97-fold; 95% CI 0.50–1.88 fold).
Increased p110α and p110β expression correlated with primary tumor size, regional lymph node metastases, and AJCC stage. Increased
p110β expression also correlated with distant metastasis. P-AKT-Thr308 and P-AKT-Ser473 expression showed significant direct
correlations with p110α and p110β mRNA expression. Besides, CRC patients with p110β mRNA overexpression had a worse disease-free
survival after radical surgery compared with those with normal or decreased levels (P = 0.043). It was, therefore, concluded that the altered p110α and p110β expression might contribute to the CRC development
or progression. |
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