Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, USA; Himalayan School of Biosciences and Cancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, India.
Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, USA.
J Adv Res. 2024 Jan;55:61-72. doi: 10.1016/j.jare.2023.02.013. Epub 2023 Feb 23.
The trends of pancreatic cancer (PanCa) incidence and mortality are on rising pattern, and it will be a second leading cause of cancer related deaths by 2030. Pancreatic ductal adenocarcinoma (PDAC), major form of PanCa, exhibits a grim prognosis as mortality rate is very close to the incidence rate, due to lack of early detection methods and effective therapeutic regimen. Considering this alarming unmet clinic need, our team has identified a novel oncogenic protein, carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7), that can be useful for spotting early events of PDAC.
This study includes bioinformatics pre-screening using publicly available cancer databases followed by molecular biology techniques in PDAC progressive cell line panel and human tissues to evaluate CEACAM7 expression in early events of pancreatic cancer.
PanCa gene and protein expression analysis demonstrated the significantly higher expression of CEACAM7 in PDAC, compared to other cancers and normal pancreas. Overall survival analysis demonstrated an association between the higher expression of CEACAM7 and poor patients' prognosis with high hazard ratio. Additionally, in a performance comparison analysis CEACAM7 outperformed S100A4 in relation to PDAC. We also observed an increase of CEACAM7 in PDAC cell line panel model. However, poorly differentiated, and normal cell lines did not show any expression. Human tissue analysis also strengthened our data by showing strong and positive IHC staining in early-stage tumors.
Our observations clearly cite that CEACAM7 can serve as a potential early diagnostic and/or prognostic marker of PDAC and may also potentiate the sensitivity of the existing biomarker panel of PDAC. However, further studies are warranted to determine its clinical significance.
胰腺癌（PanCa）的发病率和死亡率呈上升趋势，到 2030 年将成为癌症相关死亡的第二大主要原因。胰腺导管腺癌（PDAC）是 PanCa 的主要形式，由于缺乏早期检测方法和有效的治疗方案，其预后极差，死亡率非常接近发病率。考虑到这种令人担忧的临床需求未得到满足，我们的团队已经确定了一种新型致癌蛋白，即癌胚抗原相关细胞粘附分子 7（CEACAM7），它可用于发现 PDAC 的早期事件。
本研究包括使用公开可用的癌症数据库进行生物信息学预筛选，然后在 PDAC 进行分子生物学技术进展细胞系面板和人类组织中评估 CEACAM7 在胰腺癌早期事件中的表达。
PanCa 基因和蛋白表达分析表明，CEACAM7 在 PDAC 中的表达明显高于其他癌症和正常胰腺。总体生存分析表明，CEACAM7 表达较高与患者预后不良相关，风险比较高。此外，在性能比较分析中，CEACAM7 在 PDAC 方面优于 S100A4。我们还观察到 PDAC 细胞系面板模型中 CEACAM7 的增加。然而，低分化和正常细胞系没有任何表达。人类组织分析也通过显示早期肿瘤中强烈和阳性的 IHC 染色来加强我们的数据。
我们的观察结果清楚地表明，CEACAM7 可以作为 PDAC 的潜在早期诊断和/或预后标志物，并且还可能增强 PDAC 现有生物标志物面板的敏感性。然而，需要进一步的研究来确定其临床意义。
