Epigenetics Unit, Department of Surgery and Cancer, Imperial College London, 4th Floor IRDB, Hammersmith Hospital, London W12 0NN, UK.
Br J Cancer. 2012 Sep 25;107(7):1069-74. doi: 10.1038/bjc.2012.376. Epub 2012 Aug 30.
Ovarian cancer is the most lethal gynaecological cancer. Progression-free and overall survival is significantly related to surgical success and residual disease volume. It is unclear whether this survival advantage is due to an intrinsic biological element of the tumour cells which enables successful surgery and improved prognosis, or alternatively the number of tumour sustaining cells remaining irrespective of differences in biology.
A systematic review of the literature was performed identifying studies that have investigated the association between biomarkers and surgical outcomes. We attempted validation of these results using The Cancer Genome Atlas ovarian cancer data sets.
Thirty studies were identified of which sixteen determined protein expression, eight gene expression and one DNA methylation in association with surgical debulking. Individualised linear models adjusting for batch, stage and age identified only expression of the genes MTDH and insulin-like growth factor-1 receptor (IGF1R) to be significantly associated with debulking surgery (P<0.05, false discovery rate (FDR)<5%), although in the case of IGF1R this was in the opposite direction to previous findings.
The majority of studies are limited by design, include heterogeneous samples and lack adjustment for major confounding factors. High quality detailed clinical annotations should be routinely collected in future to more accurately evaluate biomarkers of surgical outcome.
卵巢癌是最致命的妇科癌症。无进展生存期和总生存期与手术成功和残留疾病体积显著相关。目前尚不清楚这种生存优势是由于肿瘤细胞的固有生物学特性使其能够成功手术和改善预后,还是由于肿瘤维持细胞的数量不受生物学差异的影响而导致的。
对文献进行系统回顾,确定了研究生物标志物与手术结果之间关联的研究。我们试图使用癌症基因组图谱卵巢癌数据集验证这些结果。
确定了 30 项研究,其中 16 项确定了与手术去瘤相关的蛋白表达,8 项确定了基因表达,1 项确定了 DNA 甲基化。个体化线性模型调整批次、分期和年龄后,仅发现 MTDH 和胰岛素样生长因子-1 受体(IGF1R)的表达与去瘤手术显著相关(P<0.05,假发现率(FDR)<5%),尽管在 IGF1R 的情况下,其与之前的发现方向相反。
大多数研究受到设计的限制,包括异质样本,并且缺乏对主要混杂因素的调整。未来应常规收集高质量详细的临床注释,以更准确地评估手术结果的生物标志物。