PIK3CA and PIK3CB expression and relationship with multidrug resistance in colorectal carcinoma

Abstract

The phosphoinositide 3-kinases (PI3Ks) are a critical family of signaling enzymes that participate in many cellular processes that promote the transformation of a normal cell into a cancer cell. These processes include cancer cell proliferation, migration, and invasion. However, the correlation between PI3Ks and multidrug resistance (MDR) remains unclear. The prognostic value of PI3Ks has not been previously evaluated. Thus, this study aims to evaluate the association between PIK3CA and PIK3CB expression and the MDR gene in colorectal cancer (CRC) patients. Immunohistochemistry was employed to detect the expressions of PIK3CA, PIK3CB, MDR-1, LRP, GST-π, and Topo II in 316 CRC specimens. Patients were followed-up annually by telephone or at an outpatient clinic. Results revealed that PIK3CA and PIK3CB expression was correlated with the degree of tumor differentiation and lymph node metastasis (P < 0.05). The overexpression of MDR-1, LRP, Topo II, and GST-π was found to be 72.78%, 70.89%, 77.53%, and 76.58% of CRC, respectively. Correlation analysis showed that PIK3CA and PIK3CB expression exhibits a positive correlation with MDR-1, LRP, and GST-π with correlation coefficients of 0.288, 0.128, and 0.197, respectively (P < 0.05). Kaplan-Meier analysis revealed that the five-year survival rate of patients without lymph node metastasis, positive expression of PIK3CA and PIK3CB, and negative expression of GST-π and MDR-1 was higher than those with these characteristics. Multivariate analysis revealed that GST-π, MDR-1 expression, and lymph node metastasis could serve as independent predictive factors of overall survival. The expression of both PIK3CA and PIK3CB is increased and related to the development and progress of colorectal carcinoma and MDR. The combined detection of PIK3CA andPIK3CB is important for patients with colorectal carcinoma in prognosis and optimal therapy.

Keywords: Colorectal cancer; MDR; PIK3CA; PIK3CB; prognosis.

Figure 1

Immunohistochemical staining of PIK3CA, PIK3CB, MDR-1, LRP, TOPII and GST-π protein expressions in CRC tissues. High-power view (Original magnification ×400) shows strong staining for PIK3CA, PIK3CB, MDR-1, LRP, and GST-π in the cytoplasm of cancer cells (A. PIK3CA; B. PIK3CB; D. LRP; F. GST-π), MDR-1 in the membrane and cytoplasm of cancer cells (C), Topo II in the nucleus of cancer cells (E).

Figure 2

Kaplan-Meier survival curves for PIK3CA/PIK3CB (A), MDR-1 (B) and GST-π (C) expression in CRC. In Kaplan-Meier analysis, high PIK3CA/PIK3CB, MDR-1, and GST-π expressions correlated with a shorter OS in CRC patients than the corresponding controls.