Department of Surgery, Trinity College Dublin, The Adelaide and Meath Hospital Incorporating the National Children's Hospital, Tallaght, Dublin 24, Ireland.
Pancreatology. 2012 Mar-Apr;12(2):130-40. doi: 10.1016/j.pan.2011.12.011. Epub 2011 Dec 31.
Molecular profiling has proven utility as a diagnostic and predictive tool in clinical oncology. However, a clinically relevant gene expression profile in pancreatic cancer remains elusive.
Primary and metastatic pancreatic cancer cell lines (BxPC-3 and AsPC-1), were stimulated with phorbol-12-myristate 13-acetate (PMA), a known inducer of cell invasion. Affymetrix gene expression microarray analysis was performed, comparing gene expression to unstimulated controls. Differential expression was identified using ArrayAssist, and confirmed using quantitative real-time PCR. Bioinformatic analysis was performed using Pathway Studio and GOstat. The derived gene expression was further validated in fresh frozen pancreatic tumour samples. The ability of the derived 3 gene expression markersto differentiate between pancreatic adenocarcinoma (PDAC) and other neoplasms, and its association with clinicopathological variables was examined.
PMA-induced significant changes in cell line gene expression, from which distinctive 3 potential invasive markers were derived. Expression of these genes, uPA, MMP-1 and IL1-R1 was confirmed in human pancreatic tumours, and was found to differentiate PDAC from other pancreatic neoplasms. The expression of IL1-R1 in PDAC is a novel finding. We found that the expression of MMP-1 was associated with high-grade PDAC (p = 0.035, Wilcoxon rank sum).
We have identified three potential invasive markers, uPA, MMP-1 and IL1-R1, whose gene expression may differentiate PDAC from other pancreatic neoplasms, and potentially reflect a more invasive phenotype.
分子谱已被证明在临床肿瘤学中是一种有诊断和预测价值的工具。然而，在胰腺癌中仍然难以找到与临床相关的基因表达谱。
用佛波醇-12-肉豆蔻酸 13-醋酸盐（PMA）刺激原发性和转移性胰腺癌细胞系（BxPC-3 和 AsPC-1），PMA 是已知的细胞侵袭诱导剂。进行 Affymetrix 基因表达微阵列分析，将基因表达与未刺激的对照进行比较。使用 ArrayAssist 识别差异表达，并使用定量实时 PCR 进行确认。使用 Pathway Studio 和 GOstat 进行生物信息学分析。在新鲜冷冻的胰腺肿瘤样本中进一步验证所得的基因表达。检查所得的 3 个基因表达标志物区分胰腺腺癌（PDAC）和其他肿瘤的能力及其与临床病理变量的关系。
PMA 诱导细胞系基因表达发生显著变化，从中衍生出 3 个潜在的侵袭性标志物。这些基因 uPA、MMP-1 和 IL1-R1 的表达在人类胰腺肿瘤中得到证实，并发现可区分 PDAC 与其他胰腺肿瘤。在 PDAC 中表达 IL1-R1 是一个新发现。我们发现 MMP-1 的表达与高级别 PDAC 相关（p = 0.035，Wilcoxon 秩和检验）。
我们已经确定了三个潜在的侵袭性标志物，uPA、MMP-1 和 IL1-R1，其基因表达可能区分 PDAC 与其他胰腺肿瘤，并可能反映出更具侵袭性的表型。
