Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. Cell-cycle-related and expression-elevated protein in tumor (CREPT) plays an important role in the phosphorylation of RNA Pol II, and has been implicated in the development of several types of cancer. As yet, however, there have been no reports on its role in PDAC. Here, we aimed to explore the value of CREPT as a prognostic biomarker in PDAC.

Methods

CREPT expression was assessed by immunohistochemistry (IHC) on a tissue microarray containing samples from 375 PDAC patients. Kaplan-Meier and Cox regression analyses were performed to explore the independent prognostic value of CREPT expression for the disease-free survival (DFS) and overall survival (OS) of PDAC patients. A Cell Counting Kit-8 (CCK8) assay was used to determine the growth rates and gemcitabine sensitivities of PDAC cells, while a Transwell assay was used to determine the migration and invasion abilities of PDAC cells. Subcutaneous xenografts were used to explore the effect of CREPT expression on tumor growth in vivo.

Results

We found that CREPT is highly expressed in tumor tissues and may serve as an independent prognostic biomarker for DFS and OS of PDAC patients. In vitro assays revealed that CREPT expression promotes the proliferation, migration, invasion and gemcitabine resistance of PDAC cells, and in vivo assays showed that CREPT expression knockdown led to inhibition of PDAC tumor growth.

Conclusions

We conclude that high CREPT expression enhances the proliferation, migration, invasion and gemcitabine resistance of PDAC cells. In addition, we conclude that CREPT may serve as an independent prognostic biomarker and therapeutic target for PDAC patients.

中文翻译：

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CREPT 作为胰腺导管腺癌生存不良的生物标志物

背景

胰腺导管腺癌 (PDAC) 是最具侵袭性的人类恶性肿瘤之一。肿瘤中细胞周期相关和表达升高的蛋白 (CREPT) 在 RNA Pol II 的磷酸化中起重要作用，并与多种癌症的发展有关。然而，到目前为止，还没有关于它在 PDAC 中的作用的报告。在这里，我们旨在探索 CREPT 作为 PDAC 预后生物标志物的价值。

方法

CREPT 表达通过免疫组织化学 (IHC) 在含有 375 名 PDAC 患者样本的组织微阵列上进行评估。进行 Kaplan-Meier 和 Cox 回归分析以探索 CREPT 表达对 PDAC 患者的无病生存 (DFS) 和总生存 (OS) 的独立预后价值。Cell Counting Kit-8 (CCK8) 测定用于测定 PDAC 细胞的生长速率和吉西他滨敏感性，而 Transwell 测定用于测定 PDAC 细胞的迁移和侵袭能力。皮下异种移植物用于探索 CREPT 表达对体内肿瘤生长的影响。

结果

我们发现 CREPT 在肿瘤组织中高表达，可作为 PDAC 患者 DFS 和 OS 的独立预后生物标志物。体外试验显示 CREPT 表达促进 PDAC 细胞的增殖、迁移、侵袭和吉西他滨耐药，体内试验表明 CREPT 表达敲低导致 PDAC 肿瘤生长的抑制。

结论

我们得出结论，高 CREPT 表达增强了 PDAC 细胞的增殖、迁移、侵袭和吉西他滨抗性。此外，我们得出结论，CREPT 可以作为 PDAC 患者的独立预后生物标志物和治疗靶点。