Laboratory of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India.
Biotherapeutics Division, National Institute of Biologicals, Noida, 201309, India.
Clin Transl Oncol. 2022 Dec;24(12):2351-2365. doi: 10.1007/s12094-022-02889-6. Epub 2022 Aug 5.
The aberrant mRNA expression of a UPR component Cation transport regulator homolog 1 (CHAC1) has been reported to be associated with poor survival in breast and ovarian cancer patients, however, the expression of CHAC1 at protein levels in malignant breast tissues is underreported. The following study aimed at analyzing CHAC1 protein expression in malignant breast cancer tissues.
Evaluation of CHAC1 expression in invasive ductal carcinomas (IDCs) with known ER, PR, and HER2 status was carried out using immunohistochemistry (IHC) with CHAC1 specific antibody. The Human breast cancer tissue microarray (TMA, cat# BR1503f, US Biomax, Inc., Rockville, MD) was used to determine CHAC1 expression. The analysis of CHAC1 IHC was done to determine its expression in terms of molecular subtypes of breast cancer, lymph node status, and proliferation index using Qu-Path software. Survival analysis was studied with a Kaplan-Meier plotter.
Immunohistochemical analysis of CHAC1 in breast cancer tissues showed significant up-regulation of CHAC1 as compared to the adjacent normal and benign tissues. Interestingly, CHAC1 immunostaining revealed high expression in tumor tissues with high proliferation and positive lymph node metastasis suggesting that CHAC1 might have an important role to play in breast cancer progression. Furthermore, high CHAC1 expression is associated with poor overall survival (OS) in large breast cancer patient cohorts.
As a higher expression of CHAC1 was observed in tissue cores with high Ki67 index and positive lymph node metastasis it may be concluded that enhanced CHAC1 expression correlates with proliferation and metastasis. The further analysis of breast cancer patients' survival data through KM plot indicated that high CHAC1 expression is associated with a bad prognosis hinting that CHAC1 may have a possible prognostic significance in breast cancer.
已有报道称，未折叠蛋白反应（UPR）成分阳离子转运调节剂同源物 1（CHAC1）的异常 mRNA 表达与乳腺癌和卵巢癌患者的不良预后相关，然而，恶性乳腺组织中 CHAC1 的蛋白水平表达却鲜有报道。本研究旨在分析恶性乳腺癌组织中 CHAC1 蛋白的表达。
采用 CHAC1 特异性抗体的免疫组织化学（IHC）方法，对已知 ER、PR 和 HER2 状态的浸润性导管癌（IDC）进行 CHAC1 表达评估。使用 Human breast cancer tissue microarray（TMA，cat#BR1503f，US Biomax，Inc.，Rockville，MD）来确定 CHAC1 的表达。采用 Qu-Path 软件分析 CHAC1 的 IHC，以确定其在乳腺癌分子亚型、淋巴结状态和增殖指数方面的表达。采用 Kaplan-Meier 绘图器进行生存分析。
与相邻正常和良性组织相比，乳腺癌组织中 CHAC1 的免疫组织化学分析显示其表达显著上调。有趣的是，CHAC1 免疫染色显示，在增殖高且有阳性淋巴结转移的肿瘤组织中高表达，表明 CHAC1 可能在乳腺癌进展中发挥重要作用。此外，在大型乳腺癌患者队列中，高 CHAC1 表达与总生存期（OS）不良相关。
由于在 Ki67 指数高和有阳性淋巴结转移的组织核心中观察到 CHAC1 表达较高，可以得出结论，增强的 CHAC1 表达与增殖和转移相关。通过 KM 图进一步分析乳腺癌患者的生存数据表明，高 CHAC1 表达与不良预后相关，提示 CHAC1 在乳腺癌中可能具有潜在的预后意义。
