Centre Léon Bérard, Département de Santé Publique, Lyon, F-69008, France.
CNRS UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Lyon, F-69373, France.
Sci Rep. 2018 May 9;8(1):7386. doi: 10.1038/s41598-018-25631-1.
After a diagnosis of colorectal cancer (CRC), approximately 50% of patients will present distant metastasis. Although significant progress has been made in treatments, most of them will die from the disease. We investigated the predictive and prognostic potential of APC11, the catalytic subunit of APC/C, which has never been examined in the context of CRC. The expression of APC11 was assessed in CRC cell lines, in tissue microarrays (TMAs) and in public datasets. Overexpression of APC11 mRNA was associated with chromosomal instability, lymphovascular invasion and residual tumor. Regression models accounting for the effects of well-known protein markers highlighted association of APC11 protein expression with residual tumor (odds ratio: OR = 6.51; 95% confidence intervals: CI = 1.54-27.59; P = 0.012) and metastasis at diagnosis (OR = 3.87; 95% CI = 1.20-2.45; P = 0.024). Overexpression of APC11 protein was also associated with worse distant relapse-free survival (hazard ratio: HR = 2.60; 95% CI = 1.26-5.37; P = 0.01) and worse overall survival (HR = 2.69; 95% CI = 1.31-5.51; P = 0.007). APC11 overexpression in primary CRC thus represents a potentially novel theranostic marker of metastatic CRC.
在诊断出结直肠癌 (CRC) 后，约有 50%的患者会出现远处转移。尽管在治疗方面取得了重大进展，但他们中的大多数仍会死于该疾病。我们研究了 APC11 的预测和预后潜力，APC11 是 APC/C 的催化亚基，以前从未在 CRC 中进行过研究。在 CRC 细胞系、组织微阵列 (TMA) 和公共数据集评估了 APC11 的表达。APC11 mRNA 的过表达与染色体不稳定性、血管淋巴管侵犯和残留肿瘤有关。回归模型考虑了众所周知的蛋白标志物的影响，突出了 APC11 蛋白表达与残留肿瘤（优势比：OR=6.51；95%置信区间：CI=1.54-27.59；P=0.012）和诊断时转移（OR=3.87；95% CI=1.20-2.45；P=0.024）的相关性。APC11 蛋白的过表达也与远处无复发生存（风险比：HR=2.60；95% CI=1.26-5.37；P=0.01）和总生存（HR=2.69；95% CI=1.31-5.51；P=0.007）更差相关。因此，原发性 CRC 中 APC11 的过表达代表了转移性 CRC 的一种潜在的新型治疗标志物。
