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巴基斯坦胰腺导管腺癌人群的蛋白质组学生物标志物分析:一项回顾性队列研究。

Proteomic biomarkers profiling in Pakistani pancreatic ductal adenocarcinoma population: a retrospective cohort study.

作者信息

Ali Saleema Mehboob, Adnan Yumna, Ahmad Zubair, Chawla Tabish, Ali Sm Adnan

机构信息

Department of Surgery, Aga Khan University Hospital, Stadium Road P.O. Box 3500, Karachi, 74800, Pakistan.

Department of Pathology & Laboratory Medicine, Aga Khan University Hospital, Stadium Road P.O. Box 3500, Karachi, 74800, Pakistan.

出版信息

Biomark Med. 2024;18(21-22):969-982. doi: 10.1080/17520363.2024.2416888. Epub 2024 Nov 7.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Research in various cancers suggests that investigating target biomarkers may provide directions to precision medicine. However, expression of biomarkers varies across different populations. The biomarker profile of Pakistani patients with PDAC remains unexplored. We conducted a study on 109 patients to analyze a panel of four proteins (KRAS, p53, BRCA1 and APC) using formalin-fixed paraffin-embedded tumor samples. After confirmation of diagnosis and appropriate tumor content, tissues were processed with antibody specific immunohistochemistry experiments. Subsequently, independent microscopic observation was conducted by two pathologists using scoring criteria specific for each antibody. Statistical analysis showed that negative expression of p53 was significantly associated with positive expression of BRCA1 ( = 0.000) and APC ( = 0.007). The expression of BRCA1 was also found significantly associated with APC ( = 0.028). None of the protein showed association with overall survival or patient demographics. Moreover, KRAS expression was shown to be significantly associated with perineural invasion ( = 0.005). This is the first study that investigates protein biomarker expression in a large cohort of Pakistani PDAC patients. The findings from the study may provide directions about the population specific biomarkers and targeted therapies for these patients.

摘要

胰腺导管腺癌(PDAC)是侵袭性最强的癌症之一。对各种癌症的研究表明,研究靶向生物标志物可能为精准医学提供方向。然而,生物标志物的表达在不同人群中存在差异。巴基斯坦PDAC患者的生物标志物谱仍未得到探索。我们对109名患者进行了一项研究,使用福尔马林固定石蜡包埋的肿瘤样本分析一组四种蛋白质(KRAS、p53、BRCA1和APC)。在确诊并确定合适的肿瘤含量后,用抗体特异性免疫组织化学实验处理组织。随后,由两名病理学家使用每种抗体特有的评分标准进行独立的显微镜观察。统计分析表明,p53的阴性表达与BRCA1(P = 0.000)和APC(P = 0.007)的阳性表达显著相关。还发现BRCA1的表达与APC显著相关(P = 0.028)。没有一种蛋白质与总生存期或患者人口统计学特征相关。此外,KRAS表达与神经周围侵犯显著相关(P = 0.005)。这是第一项在大量巴基斯坦PDAC患者队列中研究蛋白质生物标志物表达的研究。该研究结果可能为这些患者提供关于人群特异性生物标志物和靶向治疗的方向。

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