Purpose

Despite extensive biological and clinical studies, including comprehensive genomic and transcriptomic profiling efforts, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with a poor survival and limited therapeutic options. The goal of this study was to assess co-expressed PDAC proteins and their associations with biological pathways and clinical parameters.

Methods

Correlation network analysis is emerging as a powerful approach to infer tumor biology from omics data and to prioritize candidate genes as biomarkers or drug targets. In this study, we applied a weighted gene co-expression network analysis (WGCNA) to the proteome of 20 surgically resected PDAC specimens (PXD015744) and confirmed its clinical value in 82 independent primary cases.

Results

Using WGCNA, we obtained twelve co-expressed clusters with a distinct biology. Notably, we found that one module enriched for metabolic processes and epithelial-mesenchymal-transition (EMT) was significantly associated with overall survival (p = 0.01) and disease-free survival (p = 0.03). The prognostic value of three proteins (SPTBN1, KHSRP and PYGL) belonging to this module was confirmed using immunohistochemistry in a cohort of 82 independent resected patients. Risk score evaluation of the prognostic signature confirmed its association with overall survival in multivariate analyses. Finally, immunofluorescence analysis confirmed co-expression of SPTBN1 and KHSRP in Hs766t PDAC cells.

Conclusions

Our WGCNA analysis revealed a PDAC module enriched for metabolic and EMT-associated processes. In addition, we found that three of the proteins involved were associated with PDAC survival.

中文翻译：

---

胰腺癌蛋白质组的共表达分析揭示生物学和预后生物标志物。

目的

尽管进行了广泛的生物学和临床研究，包括全面的基因组和转录组分析工作，但胰腺导管腺癌 (PDAC) 仍然是一种毁灭性的疾病，生存率低且治疗选择有限。本研究的目的是评估共表达的 PDAC 蛋白及其与生物途径和临床参数的关联。

方法

相关网络分析正在成为一种强大的方法，可以从组学数据中推断肿瘤生物学，并将候选基因作为生物标志物或药物靶标进行优先排序。在这项研究中，我们将加权基因共表达网络分析 (WGCNA) 应用于 20 个手术切除的 PDAC 标本 (PXD015744) 的蛋白质组，并在 82 个独立的原发病例中证实了其临床价值。

结果

使用 WGCNA，我们获得了十二个具有不同生物学特性的共表达簇。值得注意的是，我们发现一个富含代谢过程和上皮间充质转化 (EMT) 的模块与总生存期 ( p  = 0.01) 和无病生存期 ( p  = 0.03)显着相关。属于该模块的三种蛋白质（SPTBN1、KHSRP 和 PYGL）的预后价值在 82 名独立切除患者的队列中使用免疫组织化学得到证实。在多变量分析中，预后特征的风险评分评估证实了其与总生存期的关联。最后，免疫荧光分析证实了 SPTBN1 和 KHSRP 在 Hs766t PDAC 细胞中的共表达。

结论

我们的 WGCNA 分析揭示了一个富含代谢和 EMT 相关过程的 PDAC 模块。此外，我们发现所涉及的三种蛋白质与 PDAC 存活有关。