Department of Obstetrics and Gynecology, University of Toronto, Canada.
Gynecol Oncol. 2010 Apr;117(1):9-17. doi: 10.1016/j.ygyno.2010.01.006. Epub 2010 Feb 1.
Low-grade serous carcinoma (LGSC) is a chemoresistant ovarian neoplasm thought to potentially arise in a background of low malignant potential tumors (LMP), which are typically non-aggressive. However, LMP with micropapillary features (LMP-MP) have more aggressive clinical behavior and may represent an intermediate in progression to LGSC. The objective of this study was to obtain and compare gene expression profiles of LMP, LMP-MP and LGSC to determine if LMP-MP more closely resembles LGSC, and to identify genes involved in LGSC carcinogenesis.
Epithelial cells from LMP (n=17), LMP-MP (n=9) and LGSC (n=11) were isolated by laser capture microdissection. RNA was extracted, reverse transcribed to cDNA, amplified and hybridized to Affymetrix U133 Plus2 genechip arrays. Gene expression data were checked for quality, filtered and significantly altered genes between subgroups were identified. Differential expression of selected genes was verified by RT-qPCR and immunohistochemistry.
Gene expression analysis identified differential expression between LMP and LMP-MP, LMP and LGSC but not LMP-MP and LGSC. Integration of differentially expressed genes into the protein interaction database CytoScape highlighted gene products in the MAPK pathway as differentially regulated between LMP and LGSC. Four genes were selected and validated by RT-qPCR performed on microarray samples (n=15) and immunohistochemistry on a representative microarray (n=57).
The gene expression profile of LMP-MP is similar to LGSC and distinct from LMP, reflecting their more aggressive clinical behavior. Candidate genes in the MAPK pathway were highlighted which may play a role in LGSC carcinogenesis and indicate potential therapeutic targets.
低级别浆液性癌（LGSC）是一种对化疗耐药的卵巢肿瘤，据认为可能起源于低恶性潜能肿瘤（LMP）背景下，而 LMP 通常是非侵袭性的。然而，具有微乳头状特征的 LMP（LMP-MP）具有更具侵袭性的临床行为，可能代表向 LGSC 进展的中间阶段。本研究的目的是获得并比较 LMP、LMP-MP 和 LGSC 的基因表达谱，以确定 LMP-MP 是否更类似于 LGSC，并确定参与 LGSC 发生的基因。
通过激光捕获显微切割从 LMP（n=17）、LMP-MP（n=9）和 LGSC（n=11）中分离上皮细胞。提取 RNA，反转录为 cDNA，扩增并与 Affymetrix U133 Plus2 基因芯片杂交。检查基因表达数据的质量，筛选并鉴定亚组间差异表达的基因。通过 RT-qPCR 和免疫组织化学验证选定基因的差异表达。
基因表达分析鉴定了 LMP 和 LMP-MP、LMP 和 LGSC 之间的差异表达，但 LMP-MP 和 LGSC 之间没有差异表达。将差异表达基因整合到蛋白质相互作用数据库 CytoScape 中，突出了 MAPK 通路中的基因产物在 LMP 和 LGSC 之间的差异调节。选择了四个基因，并通过在微阵列样本（n=15）上进行 RT-qPCR 和在代表性微阵列（n=57）上进行免疫组织化学验证进行验证。
LMP-MP 的基因表达谱与 LGSC 相似，与 LMP 不同，反映了其更具侵袭性的临床行为。MAPK 通路中的候选基因被突出，它们可能在 LGSC 发生中发挥作用，并表明潜在的治疗靶点。
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