Bloomston Mark, Durkin Alan, Yang Ivana, Rojiani Mumtaz, Rosemurgy Alexander S, Enkmann Steven, Yeatman Timothy J, Zervos Emmanuel E
Surgery, Moffitt Cancer Center, Tampa, Florida 33612, USA.
Ann Surg Oncol. 2004 Apr;11(4):413-9. doi: 10.1245/ASO.2004.03.077.
There is a paucity of known molecular markers that distinguish pancreatic neuroendocrine tumors from other pancreatic tumor types. We hypothesized that novel markers for pancreatic neuroendocrine tumors could be identified with molecular fingerprinting of pooled RNA samples from core biopsies.
Total RNA was harvested from nine core biopsies of normal pancreas, pancreatitis, pancreatic adenocarcinoma, pancreatic adenocarcinoma metastases, and pancreatic neuroendocrine tumors. RNA from each group of samples was pooled and hybridized to an oligonucleotide-based microarray. Four genes (ANG2, NPDC1, ELOVL4, and CALCR) were selected for further investigation by reverse transcriptase polymerase chain reaction from the top 20 highest expressed genes, on the basis of potential as novel markers.
Neuroendocrine tumors were most unique from normal pancreas. Pancreatitis, pancreatic adenocarcinoma, and metastases are more closely related to each other and to normal pancreas. ANG2 was overexpressed in 89% of neuroendocrine tumors, compared with 22% of normal pancreas, making it the best potential molecular marker or therapeutic target of the four genes selected for analysis.
We have identified a specific set of molecular markers for pancreatic neuroendocrine tumors distinct from pancreatitis and pancreatic adenocarcinoma. These novel markers may prove useful as molecular markers or therapeutic targets unique to pancreatic neuroendocrine tumors.
目前已知的能够区分胰腺神经内分泌肿瘤与其他胰腺肿瘤类型的分子标志物较少。我们推测，通过对来自核心活检样本的RNA混合样本进行分子指纹分析，可以识别出胰腺神经内分泌肿瘤的新型标志物。
从正常胰腺、胰腺炎、胰腺腺癌、胰腺腺癌转移灶以及胰腺神经内分泌肿瘤的九份核心活检样本中提取总RNA。将每组样本的RNA混合后与基于寡核苷酸的微阵列进行杂交。基于作为新型标志物的潜力，从表达量最高的前20个基因中选择四个基因（ANG2、NPDC1、ELOVL4和CALCR）进行逆转录聚合酶链反应进一步研究。
神经内分泌肿瘤与正常胰腺最为不同。胰腺炎、胰腺腺癌及其转移灶彼此之间以及与正常胰腺的关系更为密切。ANG2在89%的神经内分泌肿瘤中过表达，而在正常胰腺中这一比例为22%，使其成为所选用于分析的四个基因中最具潜力的分子标志物或治疗靶点。
我们已经确定了一组区分胰腺神经内分泌肿瘤与胰腺炎和胰腺腺癌的特定分子标志物。这些新型标志物可能作为胰腺神经内分泌肿瘤特有的分子标志物或治疗靶点而发挥作用。
