Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, People's Republic of China.
J Proteome Res. 2009 Oct;8(10):4525-35. doi: 10.1021/pr900365e.
Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis. To identify the proteins involved in colorectal carcinogenesis, we employed 2-DE and MALDI-TOF/TOF-based proteomics approach to study the differentially expressed proteins in tumor and adjacent nontumor tissue samples. Samples from 10 colorectal patients were analyzed. Of the 7 significantly and consistently altered proteins identified, hnRNP A1 was one of the most significantly altered proteins and its overexpression was confirmed using RT-PCR and Western blot analyses. Immunohistochemical examination showed that the enhanced expression of hnRNP A1 was correlated with the increasing severity of colorectal tissue and the progression of the colorectal cancer, as well as UICC (International Union against Cancer) staging, histo-differentiation, recurrence and decreased survival. By developing a highly sensitive immunoassay, hnRNP A1 could be detected in human serum and was significantly elevated in CRC patients compared with healthy volunteers. We proposed that hnRNP A1 could be considered as a novel serum tumor marker for CRC that may have significance in the detection and in the management of patients with this disease. Knockdown of hnRNP A1 expression by RNA interference led to the significant suppression of the cell growth in colorectal cancer SW480 cells in vitro. These data suggested that hnRNP A1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of colorectal cancer. Further studies are needed to fully assess the potential clinical value of this biomarker candidate.
结直肠癌（CRC）是全球第三大常见癌症，预后较差。为了鉴定参与结直肠发生的蛋白质，我们采用 2-DE 和 MALDI-TOF/TOF 基础蛋白质组学方法研究肿瘤和相邻非肿瘤组织样品中的差异表达蛋白质。对 10 例结直肠癌患者的样本进行了分析。在鉴定的 7 种显著且一致改变的蛋白质中，hnRNP A1 是改变最显著的蛋白质之一，并用 RT-PCR 和 Western blot 分析证实了其过表达。免疫组织化学检查表明，hnRNP A1 的增强表达与结直肠组织的严重程度增加、结直肠癌的进展以及 UICC（国际抗癌联盟）分期、组织分化、复发和生存率降低相关。通过开发高灵敏度免疫测定法，可以在人血清中检测到 hnRNP A1，并且与健康志愿者相比，CRC 患者的 hnRNP A1 水平显著升高。我们提出，hnRNP A1 可以被视为 CRC 的新型血清肿瘤标志物，可能对该疾病的检测和患者管理具有重要意义。hnRNP A1 表达的 RNA 干扰敲低导致结直肠癌细胞 SW480 细胞在体外的显著抑制。这些数据表明，hnRNP A1 可能是结直肠癌早期诊断、预后和监测治疗的潜在生物标志物。需要进一步研究以充分评估该生物标志物候选物的潜在临床价值。
