Department of Surgery, National University of Ireland Galway, Ireland.
J Gastrointest Oncol. 2013 Jun;4(2):144-57. doi: 10.3978/j.issn.2078-6891.2013.010.
Despite developments in diagnosis and treatment, 20% of colorectal cancer (CRC) patients present with metastatic disease and 30% of cases recur after curative surgery. Furthermore, the molecular factors involved in prognosis and response to therapy in CRC is poorly understood. The aims of this study were to quantitatively examine the expression of target genes in colorectal cancer and to correlate their expression levels with clinico-pathological variables.
A detailed analysis of published CRC microarray data was performed to identify the most prominent genes. The selected genes were validated in fifty-two pairs of fresh colorectal tumour and associated normal tissue specimens by RQ-PCR using TaqMan(®) assays. Statistical analysis and correlation with clinicopathological data was performed using SPSS software.
Expression levels of CXCL12 (P=0.000), CDH17 (P=0.026), MUC2 (P=0.000), L-FABP (P=0.000) and PDCD4 (P=0.000) were down regulated and IL8 (P=0.000) was upregulated in tumours compared to normal colorectal tissues. No significant differences were noted in expression of CEACAM5, CXCR4, CXCR7, TGFB1, TGFBR1 and TGFBR2. Furthermore, we found significant associations of gene expression levels and clinicopathological variables such as tumour size, grade, invasion and lymph node status.
We identified a comprehensive list of genes with highly differential expression patterns in colorectal cancer that could serve as molecular markers to complement existing histopathological factors in diagnosis, follow up and therapeutic strategies for individualised care of patients.
尽管在诊断和治疗方面取得了进展,但仍有 20%的结直肠癌(CRC)患者出现转移性疾病,30%的病例在根治性手术后复发。此外,CRC 中涉及预后和对治疗反应的分子因素了解甚少。本研究的目的是定量检测结直肠癌中靶基因的表达,并将其表达水平与临床病理变量相关联。
对已发表的 CRC 微阵列数据进行详细分析,以确定最突出的基因。通过 TaqMan(®)测定法使用 RQ-PCR 在 52 对新鲜结直肠肿瘤和相关正常组织标本中验证选择的基因。使用 SPSS 软件进行统计分析和与临床病理数据的相关性分析。
与正常结直肠组织相比,肿瘤中 CXCL12(P=0.000)、CDH17(P=0.026)、MUC2(P=0.000)、L-FABP(P=0.000)和 PDCD4(P=0.000)的表达水平下调,而 IL8(P=0.000)上调。CEACAM5、CXCR4、CXCR7、TGFB1、TGFBR1 和 TGFBR2 的表达无显著差异。此外,我们发现基因表达水平与肿瘤大小、分级、浸润和淋巴结状态等临床病理变量存在显著关联。
我们确定了一组在结直肠癌中具有高度差异表达模式的综合基因,这些基因可作为分子标志物,补充现有的组织病理学因素,用于诊断、随访和个体化治疗策略,以实现对患者的个体化治疗。