Mirmohseni Namini Nazanin, Abdollahi Alireza, Movahedi Monireh, Emami Razavi Amirnader, Saghiri Reza
Department of Biochemistry, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
Department of Pathology, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Pathol. 2021 Summer;16(3):284-296. doi: 10.30699/IJP.2021.135323.2482. Epub 2021 Jun 12.
BACKGROUND & OBJECTIVE: This study examined the potential of human epididymis protein 4 (HE4) as a marker in early diagnosis or as a prognostic factor for breast cancer (BC) patients.
A total of 31 patients diagnosed with BC were enrolled in the study between 2008 and 2018. The mRNA and protein expression levels of HE4 were analyzed by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR) in the BC tissue and the non-tumoral adjacent tissue. Using ELISA technique, HE4 plasma levels were also measured in 43 BC patients compared to 43 healthy individuals. The correlation between HE4 expression and clinicopathological features was then investigated.
An increase in HE4 expression was observed at mRNA and protein levels in the BC group compared to the control group (<0.01, <0.0001, respectively). In addition, the relative expression of HE4 mRNA in BC patients showed a significant correlation with the differentiation grade of cancer cells (<0.001). Plasma levels of HE4 was also associated with grade (<0.0001), stage, and tumor size in BC patients (for both <0.01). Patients with metastatic BC (<0.01), lymphatic invasion, and lymph node involvement (for both <0.05) showed significantly higher plasma levels of HE4 expression than patients without metastasis.
According to our findings, upregulation of HE4 may be related to invasive BC phenotype. Measuring plasma levels of HE4 could be useful as a screening test in early diagnosis of BC.
本研究探讨人附睾蛋白4（HE4）作为乳腺癌（BC）患者早期诊断标志物或预后因素的潜力。
2008年至2018年期间，共有31例确诊为BC的患者纳入本研究。通过免疫组织化学（IHC）和实时聚合酶链反应（PCR）分析BC组织和非肿瘤相邻组织中HE4的mRNA和蛋白表达水平。采用酶联免疫吸附测定（ELISA）技术，还对43例BC患者和43例健康个体的血浆HE4水平进行了检测。随后研究了HE4表达与临床病理特征之间的相关性。
与对照组相比，BC组的HE4在mRNA和蛋白水平上表达均增加（分别<0.01，<0.0001）。此外，BC患者中HE4 mRNA的相对表达与癌细胞分化程度显著相关（<0.001）。BC患者的血浆HE4水平也与分级（<0.0001）、分期和肿瘤大小相关（均<0.01）。发生转移的BC患者（<0.01）、有淋巴浸润和淋巴结受累的患者（均<0.05）的血浆HE4表达水平显著高于无转移的患者。
根据我们的研究结果，HE4的上调可能与浸润性BC表型有关。检测血浆HE4水平可能有助于BC的早期诊断筛查。
