School of Medicine, Institute of Medical Sciences, Örebro University, SE-70182 Örebro, Sweden.
Centre for Systems Biology, Soochow University, Suzhou 215006, China.
Int J Mol Sci. 2019 Jun 14;20(12):2919. doi: 10.3390/ijms20122919.
Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein-protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.
结肠癌是全球癌症死亡的主要原因之一。早期患者的五年生存率超过 90%，而晚期患者的生存率仅为 10%左右。此外，一半的结肠癌患者在临床上已经被诊断为晚期。因此，提高结肠癌的早期诊断能力非常重要。利用我们之前的研究结果，已经发现了几种与结肠癌早期诊断相关的潜在生物标志物。为了研究这些结肠癌的早期诊断生物标志物，我们进一步分析了人类嗜铬粒蛋白 A（CHGA）作为最强大的诊断生物标志物之一。在这项研究中，我们使用基于逻辑回归的荟萃分析来阐明 CHGA 表达与结肠癌诊断之间的关联。我们选择健康人群和结肠癌患者的正常黏膜作为双重正常对照。结果表明，与正常对照组相比，结肠癌早期 CHGA 表达降低。CHGA 在结肠癌早期表达的下降可能是一种新的诊断生物标志物，具有较高的预测可能性和验证性能，用于结肠癌的诊断。我们还将 CHGA 表达的诊断能力与典型的癌基因 KRAS、经典的肿瘤抑制基因 TP53 和众所周知的细胞增殖指数 MKI67 进行了比较，CHGA 表现出比其他癌症生物标志物更强的预测结肠癌早期诊断的能力。在蛋白质-蛋白质相互作用（PPI）网络中，CHGA 与 KRAS 和 TP53 共享一些共同的途径。CHGA 可能被认为是一种新型、有前途、强大的结肠癌早期诊断生物标志物。
