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微纤维相关蛋白 5(MFAP5)与卵巢癌患者的生存有关,但不能作为预后生物标志物。

Microfibril Associated Protein 5 (MFAP5) Is Related to Survival of Ovarian Cancer Patients but Not Useful as a Prognostic Biomarker.

机构信息

Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research of Oncology Center, Gliwice Branch, 44-102 Gliwice, Poland.

Tumor Pathology Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland.

出版信息

Int J Mol Sci. 2022 Dec 15;23(24):15994. doi: 10.3390/ijms232415994.

Abstract

Ovarian cancer (OC) is usually diagnosed late due to its nonspecific symptoms and lack of reliable tools for early diagnostics and screening. OC studies concentrate on the search for new biomarkers and therapeutic targets. This study aimed to validate the gene, and its encoded protein, as a potential prognostic biomarker. In our previous study, we found that patients with high-grade serous OC who had higher mRNA levels had shorter survival, as compared with those with lower levels. Here, we used the Kaplan-Meier Plotter and CSIOVDB online tools to analyze possible associations of expression with survival and other clinico-pathological features. In these analyses, higher mRNA expression was observed in the more advanced FIGO stages and high-grade tumors, and was significantly associated with shorter overall and progression-free survival. Next, we analyzed the expression of the MFAP5 protein by immunohistochemistry (IHC) in 108 OC samples and tissue arrays. Stronger MFAP5 expression was associated with stronger desmoplastic reaction and serous vs. non-serous histology. We found no significant correlation between IHC results and survival, although there was a trend toward shorter survival in patients with the highest IHC scores. We searched for co-expressed genes/proteins using cBioPortal and analyzed potential MFAP5 interaction networks with the STRING tool. MFAP5 was shown to interact with many extracellular matrix proteins, and was connected to the Notch signaling pathway. Therefore, although not suitable as a prognostic biomarker for evaluation with a simple diagnostic tool like IHC, MFAP5 is worth further studies as a possible therapeutic target.

摘要

卵巢癌(OC)通常由于其非特异性症状和缺乏可靠的早期诊断和筛查工具而被诊断为晚期。OC 的研究集中在寻找新的生物标志物和治疗靶点上。本研究旨在验证该基因及其编码蛋白作为潜在的预后生物标志物。在我们之前的研究中,我们发现高级别浆液性 OC 患者中 mRNA 水平较高的患者的生存率较低,与水平较低的患者相比。在这里,我们使用 Kaplan-Meier Plotter 和 CSIOVDB 在线工具来分析 表达与生存和其他临床病理特征的可能关联。在这些分析中,在更高级别的 FIGO 分期和高级别肿瘤中观察到更高的 mRNA 表达,并且与总生存期和无进展生存期较短显著相关。接下来,我们通过免疫组织化学(IHC)在 108 个 OC 样本和组织阵列中分析了 MFAP5 蛋白的表达。更强的 MFAP5 表达与更强的促结缔组织反应和浆液性与非浆液性组织学相关。我们没有发现 IHC 结果与生存之间的显著相关性,尽管在 IHC 评分最高的患者中存在生存时间较短的趋势。我们使用 cBioPortal 寻找共表达的基因/蛋白,并使用 STRING 工具分析潜在的 MFAP5 相互作用网络。MFAP5 与许多细胞外基质蛋白相互作用,并与 Notch 信号通路连接。因此,尽管 MFAP5 不适合作为简单诊断工具(如 IHC)的预后生物标志物进行评估,但它作为潜在的治疗靶点值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0091/9787877/b82984d9c90c/ijms-23-15994-g001.jpg

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