Li Huang-Bao, Zhou Jun, Zhao Fengqing, Yu Jiayin, Xu Longsheng
Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jiaxing, First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China.
Department of Pathology, First Hospital of Jiaxing, First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China.
Cancer Manag Res. 2020 Jul 20;12:5997-6006. doi: 10.2147/CMAR.S251897. eCollection 2020.
Pancreatic cancer (PC) has poor prognosis despite systemic treatment. Dehydrogenase/reductase member 9 (DHRS9) has been reported to be involved in many events of tumorigenesis, but its prognostic impact in PC remains undetermined. Thus, this study aimed to explore the association between DHRS9 expression and the prognosis of PC and investigate the possible mechanism by which DHRS9 is involved in PC progression.
The study used data: from Gene Expression Omnibus (GEO) and our institution to compare the DHRS9 expression between PC and adjacent normal tissues; from The Cancer Genome Atlas (TCGA) and our institution to assess the clinicopathological characteristics and prognosis of PC patients in high and low DHRS9 expression groups; and from TCGA to predict the potential mechanism of DHRS9 in PC. Western blot assay was used to identify DHRS9 expression in specimens collected from five patients who underwent surgery in our institute. Furthermore, immunohistochemistry (IHC) was then used to identify DHRS9 expression in the specimens of 109 patients who underwent surgery at our institute. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of DHRS9 expression among PC patients.
All the IHC, Western blot, and GEO datasets indicated that compared to normal tissues, DHRS9 was significantly overexpressed in PC tissues. IHC results demonstrated that the strong intensity of DHRS9 expression was significantly correlated with vascular infiltration (P < 0.05). Further, high DHRS9 expression was identified as a prognostic risk factor for overall survival. Functional analysis of DHRS9 co-expressed genes indicated that DHRS9 was involved in mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway.
DHRS9 is upregulated in PC tissue, and high DHRS9 expression is correlated with poor prognosis in PC. DHRS9 may affect the oncological process of PC through MAPK/ERK pathway.
尽管进行了全身治疗，胰腺癌（PC）的预后仍然很差。据报道，脱氢酶/还原酶成员9（DHRS9）参与了许多肿瘤发生事件，但其在PC中的预后影响仍未确定。因此，本研究旨在探讨DHRS9表达与PC预后之间的关联，并研究DHRS9参与PC进展的可能机制。
本研究使用了来自基因表达综合数据库（GEO）和我们机构的数据，以比较PC组织与相邻正常组织之间的DHRS9表达；使用来自癌症基因组图谱（TCGA）和我们机构的数据，评估高DHRS9表达组和低DHRS9表达组PC患者的临床病理特征和预后；并使用来自TCGA的数据预测DHRS9在PC中的潜在机制。采用蛋白质免疫印迹法检测我院5例手术患者标本中DHRS9的表达。此外，随后采用免疫组织化学（IHC）法检测我院109例手术患者标本中DHRS9的表达。采用Kaplan-Meier法和Cox回归分析法评估DHRS9表达在PC患者中的预后意义。
所有免疫组织化学、蛋白质免疫印迹和GEO数据集均表明，与正常组织相比，DHRS9在PC组织中显著过表达。免疫组织化学结果显示，DHRS9表达的高强度与血管浸润显著相关（P<0.05）。此外，高DHRS9表达被确定为总生存的预后危险因素。对DHRS9共表达基因的功能分析表明，DHRS9参与丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）信号通路。
DHRS9在PC组织中上调，高DHRS9表达与PC的不良预后相关。DHRS9可能通过MAPK/ERK途径影响PC的肿瘤发生过程。
