Biochemistry Department, B.J. Medical College, Sassoon Hospital, Pune, 411001 MH, India.
Proteomics Lab, National Centre for Cell Science, Pune, 411007 MH, India.
Proteomics Clin Appl. 2019 May;13(3):e1700119. doi: 10.1002/prca.201700119. Epub 2018 Oct 18.
The study aims to discover and identify early grade diagnosis markers in tumor microenvironment and investigates their expression in serum.
2D fluorescence difference gel electrophoresis (2D-DIGE), a gel-based proteomics platform is used for tissue profiling and identifies deregulated proteins by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Western blot validation for statistically significant six different proteins is performed in an independent cohort of participant serum.
Total 67 nonredundant tissue proteins are identified out of 230 protein spots obtained through Marker selection tool of EDA. GELS, DAPLE, IQCC, CATD, A1AT, and HS90B are selected for validation and found to be upregulated in early grade serum samples. Pathway analysis performed through PANTHER and DAVID indicates that apoptosis, CCKR, EGF, FAS, FGF, Wnt, p13 kinase, and p53 signaling pathways are expressed specifically during or early onset of grade I cancer lesions.
GELS, DAPLE, HS90B, A1AT, IQCC, and CATD may be promising potential serum biomarker signature for diagnosis of early grade breast cancer. This panel also contributes to better understanding of molecular mechanisms involved in inceptive stage of breast cancer.
本研究旨在发现和鉴定肿瘤微环境中的早期分级诊断标志物，并研究其在血清中的表达。
二维荧光差异凝胶电泳（2D-DIGE）是一种基于凝胶的蛋白质组学平台，用于组织分析，并通过基质辅助激光解吸/电离-飞行时间质谱鉴定失调蛋白。在独立的参与者血清队列中，对统计上显著的 6 种不同蛋白质进行 Western blot 验证。
通过 EDA 的 Marker selection tool 获得了 230 个蛋白点，其中鉴定出 67 个非冗余组织蛋白。GELS、DAPLE、IQCC、CATD、A1AT 和 HS90B 被选择进行验证，并发现它们在早期分级血清样本中上调。通过 PANTHER 和 DAVID 进行的途径分析表明，细胞凋亡、CCKR、EGF、FAS、FGF、Wnt、p13 激酶和 p53 信号通路在 I 级癌症病变期间或早期特异性表达。
GELS、DAPLE、HS90B、A1AT、IQCC 和 CATD 可能是早期诊断乳腺癌的有前途的潜在血清生物标志物。该面板还有助于更好地理解乳腺癌起始阶段涉及的分子机制。
