Quantitative expression analysis and prognostic significance of the novel apoptosis-related gene BCL2L12 in colon cancer

Abstract

Apoptosis is a tightly regulated process that plays a critical role in many biological events. Members of the BCL2 (Bcl-2) family of apoptosis-related genes have been found to be differentially expressed in various malignancies and have been proposed as prognostic tumor biomarkers. We have recently discovered and cloned a new member of the BCL2 gene family, BCL2L12, expressed in colon tissues. Here we have investigated expression of the BCL2L12 gene in colon cancer tissues and assessed its prognostic value. Total RNA was isolated from 96 specimens of malignant colon tissue. After testing the RNA quality, cDNA was prepared by reverse transcription. A highly sensitive real-time PCR method for BCL2L12 mRNA quantification was developed using SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative C(T) method (2(-DeltaDeltaCT)). High BCL2L12 expression levels were found in smaller (< or =5 cm, p=0.027) and well-differentiated tumors (p=0.034), as well as in early-stage tumors (p=0.039). Survival analysis demonstrated that patients with BCL2L12-positive colon tumors have significantly longer disease-free survival and overall survival (p=0.015 and p=0.027, respectively). Our results suggest that BCL2L12 gene expression may represent a potential new biomarker for colon cancer.

Effect of doxorubicin, oxaliplatin, and methotrexate administration on the transcriptional activity ofBCL-2family gene members in stomach cancer cells

“…33 Furthermore, BCL2L12 was found to be differentially expressed at the mRNA level in a series of human malignancies with potential prognostic implications. [36][37][38] In the present research work, the expression behavior of the apoptosis-associated genes BCL2L12, BAX, and BCL-2 was investigated and analyzed in the in vitro model system of stomach adenocarcinoma, 39 the AGS cells, after being subjected to the influence of the anti-neoplastic substances doxorubicin, oxaliplatin, or methotrexate. Our ultimate intent was the possible utilization of these functionally perplexing or distinct apoptotic gene members of the BCL-2 family as molecular indicators of prediction to chemotherapy in gastric cancer.…”

BCL2L12 is a Novel Biomarker for the Prediction of Short-Term Relapse in Nasopharyngeal Carcinoma

“…Expression analysis of BCL2L12 revealed that this apoptosis-related gene may be considered as a favorable prognostic biomarker for various malignancies, including breast (45,46), colon (47), and gastric cancer (48). It is worth mentioning that an association between BCL2L12 and BCL2 mRNA expression has been noticed in breast tumors (45).…”

The Novel Member of the BCL2 Gene Family, BCL2L12, Is Substantially Elevated in Chronic Lymphocytic Leukemia Patients, Supporting Its Value As a Significant Biomarker

“…Hence, novel prognostic markers are needed to stratify patients into treatment groups. Analysis of BCL2L12 mRNA expression revealed that both splicing variants of this apoptosis-related gene are overexpressed in colon cancer samples as compared to their paired normal mucosa [46,47]. Furthermore, expression of BCL2L12-A, the alternative transcript of BCL2L12, is associated with Dukes' stage and lymph node status [46], whereas higher expression of the full-length BCL2L12 variant is associated with less aggressive forms of intestinal cancer [47].…”

“…Analysis of BCL2L12 mRNA expression revealed that both splicing variants of this apoptosis-related gene are overexpressed in colon cancer samples as compared to their paired normal mucosa [46,47]. Furthermore, expression of BCL2L12-A, the alternative transcript of BCL2L12, is associated with Dukes' stage and lymph node status [46], whereas higher expression of the full-length BCL2L12 variant is associated with less aggressive forms of intestinal cancer [47]. In accordance with this finding, colon cancer patients showing BCL2L12 overexpression have significantly longer disease-free survival and OS [47], supporting the notion that BCL2L12 mRNA overexpression is related to favorable prognosis in colon cancer patients and may represent a useful tissue biomarker.…”

“…Furthermore, expression of BCL2L12-A, the alternative transcript of BCL2L12, is associated with Dukes' stage and lymph node status [46], whereas higher expression of the full-length BCL2L12 variant is associated with less aggressive forms of intestinal cancer [47]. In accordance with this finding, colon cancer patients showing BCL2L12 overexpression have significantly longer disease-free survival and OS [47], supporting the notion that BCL2L12 mRNA overexpression is related to favorable prognosis in colon cancer patients and may represent a useful tissue biomarker. Interestingly, it has recently been suggested that BCL2L12 may be regarded as a novel, independent favorable tissue biomarker in breast cancer as well, since BCL2L12-positive breast cancer patients have a lower probability of relapse and/or death, as compared to BCL2L12-negative patients [48,49].…”