Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomasn
Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomasn
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DOI：
10.1186/s12885-019-6084-4
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发表时间：
2019-09-18
期刊：
影响因子：
3.8
通讯作者：
Helou, Khalil
中科院分区：
文献类型：
--
作者：
Engqvist, Hanna;Parris, Toshima Z.;Helou, Khalil
背景：卵巢癌是妇科肿瘤相关死亡的主要原因。然而，5年生存率显着不同的五个主要卵巢癌组织类型。因此，我们需要更好地了解促进组织型特异性卵巢癌发生的机制，并确定新的预后生物标志物。（I和II）卵巢癌（n = 206），使用免疫组织化学（IHC）。我们提供了III型胶原α 1链（COL 3A 1）、G蛋白偶联受体158（GPR 158）和含PITH结构域1（PITHD 1）的异常蛋白表达模式的证据。Kaplan-Meier生存分析显示，COL 3A 1表达与四种主要组织型上皮性卵巢癌患者的总生存期缩短相关（P值= 0.026，HR = 2.99（95%CI 1.089-8.19））。此外，GPR 158和PITHD 1被证明是组织型特异性预后生物标志物，在总生存率不利的粘液性卵巢癌患者中GPR 158表达模式升高（P值= 0.00043，HR = 6.13（95% CI 1.98-18.98）），透明细胞卵巢癌患者中PITHD 1蛋白表达较低与总体和疾病特异性生存率不利相关（P值= 0.012，HR = 0.22（95%CI 0.058-0.80）; P值= 0.003，HR = 0.17（95% CI 0.043-0.64））。结论：本研究发现的新的生物标志物可能会提高诊断时的准确性，并可能有助于未来卵巢癌个体化治疗策略的发展。癌症患者。
Background: Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers.Methods: Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas (n = 206) using immunohistochemistry (IHC).Results: We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients (P value = 0.026, HR = 2.99 (95% CI 1.089-8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival (P value = 0.00043, HR = 6.13 (95% CI 1.98-18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease- specific survival in clearcell ovarian carcinoma patients (P value = 0.012, HR = 0.22 (95% CI 0.058-0.80); P value = 0.003, HR = 0.17 (95% CI 0.043-0.64)).Conclusions: The novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients.