Is Bax/Bcl-2 ratio considered as a prognostic marker with age and tumor location in colorectal cancer?

Abstract

Background: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate.

Methods: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer.

Results: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors.

Conclusion: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer.

Keywords: Colorectal cancer; Bax/Bcl-2 ratio; Bax expression; Bcl-2 expression.

Fig. 1

Correlation of Bax/Bcl-2 ratio with patient’s age. The ratio decreased in patients with age above 50, indicating an inverse correlation between Bax/Bcl-2 ratio and age.

Fig. 2

Bax/Bcl-2 relative expression in colorectal cancer cells with grade, site of primary tumor, stage, and tumor size. Panel (A) shows Bax/Bcl-2 expression ratio increases slightly from well-moderately to poorly differentiated tumors (P>0.05). Panel (B) indicates the values of Bax/Bcl-2 ratio in four different groups of primary tumor sites (mean ± SD). The ratio was significantly lower in tumors resected from colon (P value: 0.020). *Statistically significant P < 0.05. Panel (C) shows Bax/Bcl-2 relative expression in function of staging of colorectal carcinoma. This ratio was not significantly correlated with different stages of colorectal tumors (P > 0.05). Panel (D) indicates Bax/Bcl-2 relative expression with different tumor sizes ranged approximately from 2 to 8 cm in size. Bax/Bcl-2 ratio was lower in smaller tumors, but a strong correlation was not observed. ^*Statistically significant P < 0.05