Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

Abstract

Abstract. Bmi1 is overexpressed in gastrointestinal cancers, including colorectal cancer (CRC); however, its role as a non-invasive biomarker in CRC has not been established. The aim of this study was to compare the plasma Bmi1 mRNA levels prior to and following curative resection of the primary tumor in CRC patients and to determine their association with the clinicopathological parameters. The plasma Bmi1 mRNA level was measured by quantitative polymerase chain reaction and expressed as cycle threshold value. There was no significant difference between the overall pre-and postoperative plasma Bmi1 mRNA level (31.73±2.63 vs. 31.93±2.88, respectively; P=0.614) in 45 CRC patients. However, when grouped into non-metastatic and metastatic CRC patients, the postoperative Bmi1 transcript level was found to be significantly lower compared to the preoperative level in patients with non-metastatic CRC (32.13±2.677 31.44±2.764, respectively; P=0.041), whereas there was a trend towards a higher postoperative Bmi1 transcript level compared to the preoperative level in the metastatic counterpart (30.85±3.916 vs. 33.27±0.718, respectively; P=0.164). Furthermore, when the patients were categorized into two groups according to their plasma Bmi1 postoperative vs. preoperative level status, we observed that patients without a reduction in the postoperative plasma Bmi1 mRNA levels exhibited a significantly higher rate of distant metastasis following primary resection (P=0.017) and a significantly worse prognosis regarding disease-free survival (P=0.016) when compared to the reduced postoperative plasma Bmi1 level counterparts. In conclusion, plasma Bmi1 mRNA levels may serve as a non-invasive biomarker for monitoring occult metastasis and predicting the development of distant metastasis. IntroductionColorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, with >1.2 million new cancer cases and 608,700 deaths estimated to have occurred in 2008 (1). Recent advances in therapeutic strategies and surgical techniques have significantly improved the prognosis of CRC patients with primary disease; however, metastasis is a major concern for CRC patients and physicians. Thirty-five percent of CRC patients have metastatic tumors at the time of diagnosis and 33-50% of the patients without metastases will progress to stage IV during the course of their disease (1,2). Hence, it is necessary to develop prominent biomarkers for detecting the presence of occult metastasis, as well as for predicting the development of future metastasis, which may provide a useful reference for the therapeutic management of CRC patients.Potential stem cell marker, Bmi1, is a member of the polycomb-repressive complex 1, with a key role in gene silencing through chromatin modifications (3,4). In addition to the proposed role for Bmi1 as a key regulator of cell growth control/senescence mechanisms, accumulating evidence supports the role of Bmi1 in tumorigenesis. Bmi1 is overexpressed in a variety of human cancers and it...

Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development

“…In addition, BMI1 polycomb ring finger oncogene—an intestinal stem cell marker that is overexpressed in various cancers [23]–was upregulated two-fold in E . faecalis + CRCs, which is striking since high expression of BMI1 is significantly associated with metastasis [24,25] and poor survival [26] in CRC patients. Importantly, aberrant BMI1 expression has been found in premalignant gastrointestinal lesions [23], which points to its possible role in cancer initiation.…”

Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

“…48 In addition, another recent study reported that patients with decreased postoperative plasma mRNA levels of BMI1 compared to patients with increased postoperative mRNA levels correlated with a favorable prognosis in CRC. 49 These studies suggest that BMI1 may be of relevance as a prognostic indicator in CRC. However, the exact directionality of its prognostic utility remains to be elucidated.…”

Multifaceted Interpretation of Colon Cancer Stem Cells

“…This suggests that the functional significance of BMI1 is maintenance of stem cell properties in colon cancer cells. Consistent with this notion, clinical studies report that BMI1 expression is a negative predictor in colon cancer [ 72 , 73 , 74 , 75 ].…”