Serum IgG as a Marker for Opisthorchis viverrini-Associated Cholangiocarcinoma Correlated with HER2 Overexpression.
Serum IgG as a Marker for Opisthorchis viverrini-Associated Cholangiocarcinoma Correlated with HER2 Overexpression.
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DOI：
10.2147/ijgm.s282519
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发表时间：
2020
影响因子：
2.3
通讯作者：
Khuntikeo N
中科院分区：
文献类型：
--
作者：
Titapun A;Techasen A;Sa-Ngiamwibool P;Sithithaworn P;Luvira V;Srisuk T;Jareanrat A;Dokduang H;Loilome W;Thinkhamrop B;Khuntikeo N
血清间日疟原虫抗体(OV)是人感染OV病史的有力证据。目前，还没有研究检查不同的胆管癌(CCA)患病率水平是否与先前的OV感染有关，也没有提供OV相关CCA的全面评估和特征。我们的研究检测了OV阳性的CCA患者血清中的抗体水平，并确定了血清中的抗体与组织病理学特征、HER2、PD-L1和FGFR2的表达是否存在相关性，以及它们对患者生存的影响。这项研究涉及2005年至2017年在泰国坤健大学医院接受CCA手术的221名患者。用酶联免疫吸附试验检测血清OV-Ig G。用CCA组织芯片检测HER2、PD-L1和FGFR2的表达。采用Logistic回归分析各因素与免疫球蛋白的关系。用COX回归分析影响CCA患者生存的因素。卵巢抗体阳性162例，阳性率为73.3%(95%CI=68.0~78.7)。约四分之三(78.3%)为大管型肿瘤，92例(50%)伴发胆管内乳头状肿瘤。HER2阳性94例(61.4%)。PD-L1和FGFR2阳性表达分别为125例(83.9%)和100例(67.1%)。卵巢癌免疫球蛋白与组织学特征无明显相关性，但与HER2过度表达显著相关，校正OR=2.32(95%CI=1.09~4.96，P=0.03)。OV抗体阳性的CCA患者预后较差，校正后HR=1.66(95%CI=1.13~2.43，P=0.01)。我们发现OV阳性的CCA患者血清中有很高的抗体水平，并且与HER2的过度表达有关。OV免疫球蛋白和HER2表达提示CCA存活率较低。因此，未来抗HER2治疗的临床研究应该集中在OV相关的CCA。
Serum antibody for Opisthorchis viverrini (OV) is strong evidence for a history of OV infection in people. Currently, no studies have examined whether varying cholangiocarcinoma (CCA) prevalence levels are linked to previous OV infection nor have they provided comprehensive assessment and characterization of OV-associated CCA. Our study examined the prevalence of serum IgG antibodies for OV-positive CCA cases and determined whether there were correlations of IgG antibodies with histopathologic features, HER2, PD-L1, and FGFR2 expression, as well as their roles on the patients’ survival. The study involved 221 CCA surgical patients at Khon Kaen University Hospital, Thailand, from 2005 to 2017. Serum specimens were tested for OV IgG by ELISA. CCA tissue microarrays were used to examined for HER2, PD-L1, and FGFR2 expression. Logistic regression was used to investigate an association between factors and IgG. Cox regression was used to determine factors that affected CCA patient survival. IgG for OV were positive in 162 cases, and the prevalence was 73.3% (95% CI=68.0–78.7). About three quarters (78.3%) had large duct type tumors and concomitant intraductal papillary neoplasm of bile ducts (IPNB) occurred in 92 (50%) cases. HER2 expression was positive in 94 (61.4%) cases. Positive PD-L1 and FGFR2 expression occurred in 125 (83.9%) and 100 (67.1%) cases. IgG for OV had no significant correlation to any histological feature but had significant correlation with HER2 overexpression with adjusted OR=2.32 (95% CI=1.09–4.96, P=0.03). Cases of CCA with OV IgG positive had a significantly poor prognosis with adjusted HR=1.66 (95% CI=1.13–2.43, P=0.01). We found a high prevalence of serum IgG for OV-positive CCA patients and a correlation with overexpression of HER2. Moreover, IgG for OV and HER2 expression indicated poor survival of CCA. Therefore, future clinical studies for anti-HER2 treatments should focus on OV-associated CCA.