Kirana Chandra, Shi Hongjun, Laing Emma, Hood Kylie, Miller Rose, Bethwaite Peter, Keating John, Jordan T William, Hayes Mark, Stubbs Richard
Wakefield Biomedical Research Unit, University of Otago, Wellington 6242, New Zealand.
Int J Proteomics. 2012;2012:245819. doi: 10.1155/2012/245819. Epub 2012 Aug 7.
Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC) remains disappointing with some 40-50% of newly diagnosed patients ultimately dying of metastatic disease. Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy. We have identified that cathepsin D expression was significantly greater in cells from invasive front (IF) area and liver metastasis (LM) than those from main tumour body (MTB). Cathepsin D expression was subsequently examined by immunohistochemistry in tissue microarrays from 119 patients with CRC. Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival. However, cathepsin D expression in cells from the MTB was highly elevated in late stage CRC and showed significant correlation with subsequent distant metastasis and shorter cancer-specific survival. We also found that macrophages surrounding tumour cells stained strongly for cathepsin D but there was no significant correlation found between cathepsin D in macrophages at IF and MTB of CRC patient with the clinic-pathological parameters examined.
尽管外科技术和治疗方法最近取得了进展，但结直肠癌（CRC）患者的生存率仍然令人失望，约40-50%新诊断的患者最终死于转移性疾病。目前仅通过光学显微镜进行的分期对预后的预测不够充分，需要生物标志物的额外支持，以便为辅助治疗对患者进行适当分层。我们发现，组织蛋白酶D在侵袭前沿（IF）区域和肝转移（LM）细胞中的表达明显高于主要肿瘤主体（MTB）细胞。随后，通过免疫组织化学对119例CRC患者组织芯片中的组织蛋白酶D表达进行了检测。IF处肿瘤细胞中的强表达与所检查的任何临床病理参数或患者生存率均无显著相关性。然而，MTB细胞中的组织蛋白酶D表达在晚期CRC中高度升高，且与随后的远处转移和较短的癌症特异性生存期显著相关。我们还发现，肿瘤细胞周围的巨噬细胞组织蛋白酶D染色强烈，但CRC患者IF和MTB处巨噬细胞中的组织蛋白酶D与所检查的临床病理参数之间未发现显著相关性。
