Institute of Bioinformatics, International Technology Park, Bangalore, India.
Cancer Biomark. 2012;12(1):1-9. doi: 10.3233/CBM-120289.
The pathogenesis of esophageal squamous cell carcinoma (ESCC) involves both genetic and environmental factors. Previously, we have carried out gene and protein expression profiling of ESCC using DNA microarrays and mass spectrometry-based quantitative proteomics, respectively. These studies resulted in identification of several potential biomarkers of ESCC, some with known reports of differential expression in the scientific literature and others that were novel observations from our studies. We report systematic validation of selected markers from our studies on a larger cohort of cancer tissue sections by immunohistochemical labeling of tissue microarrays. We have validated expression of insulin-like growth factor-binding protein 7 (IGFBP7), stanniocalcin 2 (STC2), inhibin beta A (INHBA) and four and a half LIM domains 1 (FHL1). Immunohistochemical labeling with anti-stanniocalcin 2 antibody demonstrated its overexpression in 132/140 (94%) cases, IGFBP7 showed overexpression in 127/140 (91%) cases and overexpression of INHBA was observed in 62/105 (59%) of ESCC cases. In contrast, FHL1 expression was observed only in 12/143 (8%) of ESCC cases suggesting its possible involvement in tumor suppression. These data suggest that IGFBP7, INHBA, STC2 and FHL1 might play an important role in ESCC tumorigenesis, which can be explored in future studies. Overall, our findings open up new avenues for development of novel therapeutics and/or diagnostic approaches in ESCC.
食管鳞状细胞癌（ESCC）的发病机制涉及遗传和环境因素。此前，我们分别使用 DNA 微阵列和基于质谱的定量蛋白质组学对 ESCC 进行了基因和蛋白质表达谱分析。这些研究确定了几个 ESCC 的潜在生物标志物，其中一些在科学文献中有已知的差异表达报道，另一些则是我们研究中的新观察结果。我们通过组织微阵列的免疫组织化学标记，对我们研究中选择的标记物在更大的癌症组织切片队列中进行了系统验证。我们验证了胰岛素样生长因子结合蛋白 7（IGFBP7）、卵母细胞成熟因子 2（STC2）、抑制素βA（INHBA）和四个半 LIM 结构域 1（FHL1）的表达。用抗 STC2 抗体进行免疫组织化学标记表明，在 132/140（94%）例中存在过度表达，IGFBP7 在 127/140（91%）例中存在过度表达，INHBA 在 62/105（59%）例 ESCC 病例中存在过度表达。相比之下，FHL1 仅在 12/143（8%）例 ESCC 病例中观察到表达，提示其可能参与肿瘤抑制。这些数据表明，IGFBP7、INHBA、STC2 和 FHL1 可能在 ESCC 肿瘤发生中发挥重要作用，这可以在未来的研究中进一步探索。总的来说，我们的发现为 ESCC 的新型治疗和/或诊断方法的开发开辟了新的途径。
