Loren Masterson, Bryan J Thibodeau, Laura E Fortier, Timothy J Geddes, Barbara L Pruetz, Rajwant Malhotra, Richard Keidan, George D Wilson
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引用次数: 9
摘要
由于默克尔细胞癌(MCC)的罕见性,前瞻性临床试验尚未实现。本研究旨在确定具有预后意义的生物标志物。在我们的机构中,有62名患者接受了MCC的治疗,但只有17名患者有足够的福尔马林固定石蜡包埋档案组织和随访被纳入研究。患者被分为良好、中度和不良预后。采用激光捕获显微解剖分离肿瘤细胞,随后用Affymetrix GeneChip Human Exon 1.0 ST阵列进行RNA分离和基因表达分析。在预后组之间表现出显著差异表达的191个基因中,角蛋白20和神经丝蛋白先前已在MCC研究中被发现,并且在预后不良患者的肿瘤中显著上调。免疫组化进一步证实角蛋白20在预后不良肿瘤中过表达。此外,新的相关基因如磷脂酶A2组X、激酶家族成员3A、肿瘤蛋白D52、粘蛋白1和KIT在预后不良患者的标本中上调。我们的初步研究确定了几个基因表达差异,这些差异可以在未来用作MCC患者的预后生物标志物。
Due to the rarity of Merkel cell carcinoma (MCC), prospective clinical trials have not been practical. This study aimed to identify biomarkers with prognostic significance. While sixty-two patients were identified who were treated for MCC at our institution, only seventeen patients had adequate formalin-fixed paraffin-embedded archival tissue and followup to be included in the study. Patients were stratified into good, moderate, or poor prognosis. Laser capture microdissection was used to isolate tumor cells for subsequent RNA isolation and gene expression analysis with Affymetrix GeneChip Human Exon 1.0 ST arrays. Among the 191 genes demonstrating significant differential expression between prognostic groups, keratin 20 and neurofilament protein have previously been identified in studies of MCC and were significantly upregulated in tumors from patients with a poor prognosis. Immunohistochemistry further established that keratin 20 was overexpressed in the poor prognosis tumors. In addition, novel genes of interest such as phospholipase A2 group X, kinesin family member 3A, tumor protein D52, mucin 1, and KIT were upregulated in specimens from patients with poor prognosis. Our pilot study identified several gene expression differences which could be used in the future as prognostic biomarkers in MCC patients.
期刊介绍:
Journal of Skin Cancer is a peer-reviewed, Open Access journal that publishes clinical and translational research on the detection, diagnosis, prevention, and treatment of skin malignancies. The journal encourages the submission of original research articles, review articles, and clinical studies related to pathology, prognostic indicators and biomarkers, novel therapies, as well as drug sensitivity and resistance.