Clinical features of cystatin A expression in patients with pancreatic ductal adenocarcinoma.

Clinical features of cystatin A expression in patients with pancreatic ductal adenocarcinoma.
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DOI:
10.1111/cas.13396
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发表时间:
2017-11
期刊:
影响因子:
5.7
通讯作者:
Sakai Y
Sakai Y
中科院分区:
医学2区
文献类型:
--
作者:
Komura T;Takabatake H;Harada K;Yamato M;Miyazawa M;Yoshida K;Honda M;Wada T;Kitagawa H;Ohta T;Kaneko S;Sakai Y

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胰腺导管腺癌(PDAC)是已知的最致命的恶性肿瘤,由于缺乏有效的诊断方案,除了手术外没有根治性治疗选择,预后极差。因此,了解PDAC的病理生理学,并找到一种新的生物标志物来检测PDAC,应该优先考虑。我们观察到的半胱氨酸蛋白酶抑制剂半胱氨酸蛋白酶抑制剂A(CSTA)的mRNA表达增加的CD4+ T细胞在9例PDAC患者的外周血细胞,与7名健康志愿者的表达相比。此外,我们证实,在一个更大的队列中,41例PDAC患者的CSTA mRNA表达显著高于20例健康志愿者。36例PDAC患者血清CSTA浓度高于37例健康志愿者,且与PDAC临床分期有关。此外,通过免疫组织化学染色,在20例手术切除的PDAC组织的肿瘤组织和肿瘤浸润免疫细胞中观察到CSTA和组织蛋白酶B(一种受CSTA抑制的溶酶体半胱氨酸蛋白酶)的表达。在一些肿瘤组织和许多肿瘤浸润性免疫细胞中检测到CSTA的表达。在大多数肿瘤组织和肿瘤浸润免疫细胞中也观察到组织蛋白酶B表达。总之,CSTA及其底物组织蛋白酶B参与PDAC相关炎症。PDAC患者外周血中CSTA表达的增加可能具有作为PDAC免疫病理生物标志物的潜在作用。
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy known, with an extremely poor prognosis due to the lack of an efficient diagnostic scheme and no radical treatment option, except surgery. Therefore, understanding the pathophysiology of, and finding a novel biomarker to detect, PDAC should be prioritized. We observed an increase in mRNA expression of the cysteine protease inhibitor cystatin A (CSTA) in CD4+ T cells in peripheral blood cells of nine patients with PDAC, compared with the expression in seven healthy volunteers. Moreover, we confirmed significantly higher CSTA mRNA expression in a larger cohort of 41 patients with PDAC compared with that in 20 healthy volunteers. Correspondingly, the serum CSTA concentrations in 36 patients with PDAC were higher than those in 37 healthy volunteers, and this increase was correlated with PDAC clinical stage. Furthermore, the expression of CSTA and cathepsin B, which is a lysosomal cysteine protease inhibited by CSTA, was observed in tumor tissues and tumor‐infiltrating immune cells in 20 surgically resected PDAC tissues by immunohistochemical staining. Expression of CSTA was detected in some tumor tissues and many tumor‐infiltrating immune cells. Cathepsin B expression was also observed in most tumor tissues and tumor‐infiltrating immune cells. In conclusion, CSTA and its substrate cathepsin B are involved in PDAC‐related inflammation. The increment of CSTA expression in peripheral blood of patients with PDAC may have a potential role as a PDAC immunopathologic biomarker.
DOI: 10.1111/cas.12663
发表时间: 2015-06
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影响因子: 5.7
作者:
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