ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER?

ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

摘要
背景：CD133与AXL已被证实为癌症干细胞标志物，c-MYC则是结直肠癌（colorectal cancer, CRC）中关键的细胞调控机制。
研究目的：评估生物标志物CD133、AXL及c-MYC的预后作用，及其在结直肠腺癌与结直肠腺瘤中的临床病理特征相关性。
方法：本研究共纳入156例患者，其中国际抗癌联盟（Union for International Cancer Control, UICC）I~IV期腺癌患者122例、腺瘤患者34例。采用组织微阵列（tissue microarrays, TMA）技术检测原发肿瘤与息肉组织中CD133、c-MYC及AXL的表达水平，并分析其与临床病理特征的相关性。
结果：低分化腺癌与疾病进展是不良总生存期的独立危险因素。本研究的中位总生存期为30个月。单因素分析显示，CD133阳性表达（占所有病例的35.9%），尤其是右侧结直肠癌患者（占CD133阳性病例的44.8%），与死亡风险降低呈负相关，但该相关性在多因素分析中未达到统计学显著性。c-MYC阳性表达（占所有病例的15.4%）主要见于伴远处（非肺/非肝）转移的晚期患者。AXL表达仅偶见，且主要集中于腺瘤患者，在高级别异型增生中检出率更低。
结论：结直肠癌中CD133表达与不良总生存期无显著相关性。尽管AXL的检测结果尚不明确，但原发性结直肠癌中c-MYC表达与远处转移密切相关。