Objective

Endometrial cancer is the most common gynecologic cancer and yet much is still unknown about this disease. Our goal was to identify unique biomarkers of disease by performing a comprehensive proteomic analysis of early stage, low-grade endometrial cancer through analysis of serum collected from patients pre- and post-definitive surgery.

Methods

We used mass spectrometry (MS)-based proteomics to identify serum proteins from these patients. Serum samples from women undergoing hysterectomy with bilateral salpingo-oophorectomy for benign reasons served as control samples for the correlative studies. We then correlated our findings with The Cancer Genome Atlas (TCGA) database for additional confirmation.

Results

The Ingenuity Pathway Analysis of proteins that were differentially expressed in endometrial cancer showed increased cell survival and decreased organismal death, the most common hallmarks of cancer. We identified over expression of FAM83D (family with sequence similarity 83, member D) in the serum of patients with early stage low-grade endometrial cancer and verified the same in the endometrial cancer cell lines and patient tumors. We also confirmed our hypothesis that FAM83D may serve as a biomarker for endometrial cancer in a cohort of patients with endometrial cancer from The Cancer Genome Atlas (TCGA) project.

Conclusion

Comprehensive proteomic analysis is a feasible strategy for potential biomarker identification. Using this technique, FAM83D was identified as a candidate biomarker in early endometrial cancer in our patient samples and was not present in benign control samples. FAM83D has been associated with poor clinical outcomes in several human malignancies.

Significance

Our manuscript describes an alternative approach to comprehensive protein analysis in a model pre and post tumor removal for a sample of patients with early endometrial cancer. The model is innovative and the findings of over expression FAM83D in this population of early cancer may be useful in the study of a disease where there are few biomarkers or targetable therapies.

中文翻译：

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早期子宫内膜癌的全面血清蛋白质组学分析

目的

子宫内膜癌是最常见的妇科癌，但对该病仍知之甚少。我们的目标是通过对从明确手术前后患者收集的血清进行分析，对早期，低度子宫内膜癌进行全面的蛋白质组分析，从而确定疾病的独特生物标志物。

方法

我们使用基于质谱（MS）的蛋白质组学来鉴定这些患者的血清蛋白。由于良性原因接受双侧输卵管卵巢切除术的妇女行子宫切除术的血清样本作为相关研究的对照样本。然后，我们将研究结果与癌症基因组图谱（TCGA）数据库相关联，以进行进一步确认。

结果

子宫内膜癌中差异表达的蛋白质的“机能途径分析”显示，细胞存活率提高和生物死亡减少，这是癌症最常见的标志。我们在早期低度子宫内膜癌患者的血清中鉴定了FAM83D（序列相似性为83的家庭，成员D）的过表达，并在子宫内膜癌细胞系和患者肿瘤中验证了其高表达。我们还证实了这一假设，即FAM83D可以作为来自癌基因组图谱（TCGA）项目的子宫内膜癌患者队列的子宫内膜癌生物标志物。

结论

全面的蛋白质组分析是潜在的生物标志物鉴定的可行策略。使用这种技术，FAM83D被确定为我们患者样品中早期子宫内膜癌的候选生物标志物，并且在良性对照样品中不存在。FAM83D与几种人类恶性肿瘤的不良临床结果相关。

意义

我们的手稿描述了对早期子宫内膜癌患者进行肿瘤切除之前和之后的模型中全面蛋白质分析的另一种方法。该模型具有创新性，在这种早期癌症人群中过表达FAM83D的发现可能对研究缺乏生物标志物或靶向疗法的疾病有用。