Stromal expression of hemopexin is associated with lymph-node metastasis in pancreatic ductal adenocarcinoma
Stromal expression of hemopexin is associated with lymph-node metastasis in pancreatic ductal adenocarcinoma
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DOI：
10.1371/journal.pone.0235904
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发表时间：
2020-07-14
期刊：
影响因子：
3.7
通讯作者：
Unno, Michiaki
中科院分区：
文献类型：
--
作者：
Suzuki, Yukie;Takadate, Tatsuyuki;Unno, Michiaki
胰腺导管腺癌是最具侵袭性的癌症类型之一。肿瘤微环境中的某些蛋白质由于与肿瘤侵袭和转移相关而引起了人们的广泛关注。在这里，我们使用蛋白质组学来鉴定与淋巴结转移相关的蛋白质，淋巴结转移是预后因素之一。我们选择了在2005年至2015年期间接受胰腺切除术的淋巴结转移阳性和阴性患者（各n = 5），并进行了肿瘤基质的全面蛋白质组学分析。通过质谱法共检测到490种蛋白质。软件分析显示，这些蛋白质中有9种在两个患者组之间差异表达。基于免疫组化结果，我们集中于血红素结合蛋白和铁蛋白轻链。我们评估了163例患者的临床病理学数据，发现血红素结合蛋白表达与UICC N2（p= 0.0399）、淋巴结比率（p= 0.0252）、静脉浸润（p= 0.0096）和淋巴浸润（p= 0.0232）相关。值得注意的是，体外试验表明，血红素结合蛋白促进胰腺癌细胞的侵袭。我们的研究结果表明，血红素结合蛋白是一种淋巴结转移相关蛋白，可能成为胰腺导管腺癌的一个有用的治疗靶点或生物标志物。
Pancreatic ductal adenocarcinoma is one of the most aggressive types of cancer. Certain proteins in the tumor microenvironment have attracted considerable attention owing to their association with tumor invasion and metastasis. Here, we used proteomics to identify proteins associated with lymph-node metastasis, which is one of the prognostic factors. We selected lymph node metastasis-positive and -negative patients (n = 5 each) who underwent pancreatectomy between 2005 and 2015 and subjected to comprehensive proteomic profiling of tumor stroma. A total of 490 proteins were detected by mass spectrometry. Software analysis revealed that nine of these proteins were differentially expressed between the two patient groups. We focused on hemopexin and ferritin light chain based on immunohistochemistry results. We assessed the clinicopathological data of 163 patients and found that hemopexin expression was associated with UICC N2 (p= 0.0399), lymph node ratio (p= 0.0252), venous invasion (p= 0.0096), and lymphatic invasion (p= 0.0232). Notably,in vitroassays showed that hemopexin promotes invasion of the pancreatic cancer cells. Our findings suggest that hemopexin is a lymph node metastasis-associated protein that could potentially serve as a useful therapeutic target or biomarker of pancreatic ductal adenocarcinoma.