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评估HMGB1表达作为胆管癌临床生物标志物的作用

Evaluation of HMGB1 Expression as a Clinical Biomarker for Cholangiocarcinoma.

作者信息

Amontailak Supakan, Titapun Attapol, Jusakul Apinya, Thanan Raynoo, Kimawaha Phongsaran, Jamnongkan Wassana, Thanee Malinee, Sirithawat Papitchaya, Haohan Songpol, Techasen Anchalee

机构信息

Medical Science Program, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.

Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.

出版信息

Cancer Genomics Proteomics. 2025 Jan-Feb;22(1):81-89. doi: 10.21873/cgp.20489.

DOI:10.21873/cgp.20489
PMID:39730185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11696321/
Abstract

BACKGROUND/AIM: Cholangiocarcinoma (CCA) is an epithelial malignancy that is most prevalent in Southeast Asia, particularly in the northeast of Thailand. Identifying and establishing specific biomarkers of CCA is crucial for ensuring accurate prognosis and enabling effective treatment. High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that can be released by dead or injured cells and is associated with tumor progression. This study aimed to investigate the expression levels of HMGB1 in CCA.

MATERIALS AND METHODS

The clinical significance of HMGB1 levels was assessed by examining their correlation with patients' clinicopathological data. A bioinformatics analysis was conducted to examine HMGB1 mRNA expression and perform survival analysis. The expression levels of 137 tissue cases were evaluated using the immunohistochemical technique, whereas the serum levels of 31 cases were evaluated using indirect ELISA.

RESULTS

The GEPIA analysis demonstrated that HMGB1 exhibited elevated mRNA expression in CCA compared to the normal group. Immunohistochemical staining revealed that HMGB1 expression was primarily localized in the nucleus. High HMGB1 expression was observed in 57.6% of tissue samples, while low expression was detected in 42.4%. There was a significant positive correlation between high HMGB1 expression and the extrahepatic type of CCA as well as lymph node metastasis. The measurement of HMGB1 levels were assessed using indirect ELISA in 31 CCA serum samples, where 51.6% exhibited elevated concentrations of HMGB1. Elevated serum HMGB1 levels were significantly associated with advanced tumor stages and high levels of bilirubin levels.

CONCLUSION

HMGB1 in both tissue biopsies and blood serum shows potential as a predictive biomarker in CCA patients. These biomarkers could form the basis for facilitating more effective treatment planning.

摘要

背景/目的:胆管癌(CCA)是一种上皮性恶性肿瘤,在东南亚地区最为常见,尤其是在泰国东北部。识别和建立CCA的特定生物标志物对于确保准确的预后和实现有效治疗至关重要。高迁移率族蛋白B1(HMGB1)是一种损伤相关分子模式(DAMP)分子,可由死亡或受损细胞释放,并与肿瘤进展相关。本研究旨在调查HMGB1在CCA中的表达水平。

材料与方法

通过检查HMGB1水平与患者临床病理数据的相关性来评估其临床意义。进行生物信息学分析以检查HMGB1 mRNA表达并进行生存分析。使用免疫组织化学技术评估137例组织病例的表达水平,而使用间接ELISA评估31例病例的血清水平。

结果

GEPIA分析表明,与正常组相比,CCA中HMGB1的mRNA表达升高。免疫组织化学染色显示,HMGB1表达主要定位于细胞核。在57.6%的组织样本中观察到高HMGB1表达,而在42.4%中检测到低表达。高HMGB1表达与肝外型CCA以及淋巴结转移之间存在显著正相关。使用间接ELISA对31份CCA血清样本中的HMGB1水平进行测量,其中51.6%的样本中HMGB1浓度升高。血清HMGB1水平升高与晚期肿瘤阶段和高水平胆红素显著相关。

结论

组织活检和血清中的HMGB1均显示出作为CCA患者预测生物标志物的潜力。这些生物标志物可为促进更有效的治疗计划奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/712394c92e70/cgp-22-86-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/b59d6c6c531f/cgp-22-84-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/630dc35b78af/cgp-22-85-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/f66f31b1ca53/cgp-22-85-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/712394c92e70/cgp-22-86-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/b59d6c6c531f/cgp-22-84-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/630dc35b78af/cgp-22-85-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/f66f31b1ca53/cgp-22-85-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3379/11696321/712394c92e70/cgp-22-86-g0001.jpg

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本文引用的文献

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Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage.HMGB1在人胆管癌中的亚细胞定位:与肿瘤分期的相关性
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Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women.白人女性和黑人女性中雌激素受体表达与乳腺癌特异性死亡风险的定量测量。
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