The association of apoptotic protein expressions sensitive to apoptosis gene, p73 and p53 with the prognosis of cervical carcinoma

Abstract

ObjectiveTo evaluate the expressions of several apoptotic pathway proteins in relation to clinical parameters and survival in patients with cervical carcinoma.MethodsA total of 20 patients with clinically advanced staged carcinoma of cervix (International Federation of Gynecology and Obstetrics [FIGO] stage IIB-IVA) aged from 40 to 75 years were included in this study. The expression profile of anti-apoptotic protein (sensitive to apoptosis gene [SAG]), mitochondrial apoptotic proteins (B-cell lymphoma-extra-large [Bcl-xL] and Bcl-2 homologous antagonist/killer [Bak]), and tumor suppressor proteins (p73 and p53) were examined by real-time polymerase chain reaction experiments along with their relation to clinical parameters and survival analyses during follow-up for 5 to 8 years.ResultsNo significant difference was found in the expressions of SAG, Bcl-xL, Bak, p73 and p53 proteins with respect to stage and grade of tumor. A significant positive correlation was noted between SAG and Bcl-xL genes (r=0.752, P<0.001) and between SAG and Bak genes (r=0.589, P=0.006). Among genes determined to be significantly associated with overall survival in the univariate analysis (P=0.026 for SAG, P=0.002 for Bcl-xL, and P=0.027 for p53), only p53 was identified as the significant predictor in the multivariate analysis (hazard ratio: 8.53, 95% confidence interval: 1.34–54.2, P=0.023).ConclusionIn conclusion, our findings demonstrated a reverse correlation of SAG, Bcl-xL, and p53 expressions with overall survival of patients. No association of apoptotic pathway proteins with clinicopathological characteristics of cervical carcinoma patients was noted. Low SAG, Bcl-xL, and p53 expression levels revealed to be useful as prognostic predictors in patients with cervical carcinoma.

Apoptotic Effects of Etodolac in Breast Cancer Cell Cultures

“…SAG levels were found to be higher in malignant cells and indicated as a potential prognostic marker at several cancer types [47,48]. We found a reverse correlation of SAG, Bcl-xL and p53 expressions and overall survival of the advanced stage cervical carcinoma patients, as well as rectal cancer patients [49]. Apoptotic efects of SAG silencing were investigated in diferent cancer cell lines.…”

Cervical Carcinoma: Oncobiology and Biomarkers

“…No association of proteins of the apoptotic pathway with the clinical and pathological characteristics of patients was found; no significant differences in the expression of proteins SAG, Bcl-xL, Bak, p73, and p53, depending on the stage and degree of the tumor, were revealed. Low expression levels of SAG, Bcl-xL, and p53 were found to be useful as prognostic predictors in patients with cervical carcinoma [42].…”

“…HPV DNA, E6/E7 mRNA p53, Rb, p16INK4a, telomerase RNA gene (TERC), serum SCC-Ag, OCVA1 [8,[10][11][12][13]15,[20][21][22][23][24][25][26] Markers of cell cycle and proliferation Ki-67, cyclin D1, p53, p63 [12,[26][27][28][29][30][31][32][33][34][35][36] Markers of apoptosis P53, BCL-2, BCL-XL, BAX [10,27,[37][38][39][40][41][42][43][44] Expression of cytokeratins-markers of differentiation CK7, CK8, CK17, CK19 [27,36,37,[45][46][47][48][49] Markers of cell adhesion, invasion and metastasis E-cadherin, P-cadherin, CD44, ADAM9, MT1-MMP, TIMP-1, TIMP-2, MT1-MMP, MMP-2, MMP-1, MMP-9, MMP-14, proMMP-14 furin, gelatinase, TIMP-1 and TIMP-2 [27,[50][51][52]…”

“…Negative correlation of the expression profile of the anti-apoptotic proteins SAG, Bcl-xL, and p53 with the overall survival of patients with cervical cancer stages IIB-IVA has been demonstrated. The expression profile of the anti-apoptotic protein SAG, mitochondrial apoptotic proteins Bcl-xL and Bak, and tumor suppressor proteins p73 and p53 was studied by real-time PCR to evaluate their relationship with clinical parameters and survival during the observation period [42]. No association of proteins of the apoptotic pathway with the clinical and pathological characteristics of patients was found; no significant differences in the expression of proteins SAG, Bcl-xL, Bak, p73, and p53, depending on the stage and degree of the tumor, were revealed.…”