Nastase A, Pâslaru L, Niculescu A M, Ionescu M, Dumitraşcu T, Herlea V, Dima S, Gheorghe C, Lazar V, Popescu I
Molecular biology and biobanking laboratory, Rntech, Bucharest, Romania.
Chirurgia (Bucur). 2011 Mar-Apr;106(2):177-85.
An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.
当今研究的一个重要目标是发现能够在早期阶段检测结肠肿瘤并准确指示疾病状态的新生物标志物。我们研究的目的是确定结肠癌发生和进展的潜在生物标志物。我们通过定量实时PCR评估了从20名患者手术期间收集的同一患者的结肠黏膜三联体（正常、腺瘤、肿瘤组织）中10个候选基因（MMP-1、MMP-3、MMP-7、DEFA 1、DEFA-5、DEFA-6、IL-8、CXCL-1、SPP-1、CTHRC-1）的基因表达谱。此外，我们对DEFA1-3和SPP1进行了免疫组织化学检测。我们发现DEFA5和DEFA6是腺瘤形成的关键因素（p<0.05）。MMP7在从良性到恶性状态的转变中很重要（p <0.01），并且在转移过程中进一步作为肿瘤转化和癌细胞转移潜能的预后指标。无论肿瘤分期如何，IL8在腺癌中的mRNA水平都很高（p< 0.05）。SPP1的表达水平与肿瘤水平相关。我们建议，高水平的DEFAS、DEFA6（腺瘤形成的关键因素）、MMP7（结肠癌发生和转移进展的标志物）、SPP1（进展标志物）和IL8可用于诊断早期结肠癌并评估结肠肿瘤进展的预后。此外，如果DEFA5和DEFA6的表达水平低但MMP7、SPP1和IL8水平高，我们可以指出从腺瘤到腺癌的转变已经发生。因此，DEFA5、DEFA6、MMP7、IL8和SPP1构成了一组有价值的生物标志物，其检测可用于结肠癌的早期检测、疾病进展评估以及预后判断。
