Watson Martin M, Søreide Kjetil
Gastrointestinal Translational Research Unit, Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway.
Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
Mol Med. 2016 Sep;22:271-273. doi: 10.2119/molmed.2016.00098. Epub 2016 May 4.
The TNM-system fails to accurately predict disease recurrence in a considerate number of patients. While node-negative (stage II) colon cancer is considered to have an overall good prognosis, the 5-year cancer-specific survival is reported at 81-83% in patients who did not have adjuvant chemotherapy. Thus, reliance on node-status alone has lead to under-treatment in a subgroup of stage II patients with an unfavorable prognosis. The search for new and better prognosticators in stage II colon cancer has suggested several proposed biomarkers of better prognostication and prediction. However, few such biomarkers have reached widespread clinical utility. For the clinician swimming in the sea of emerging biomarkers, it may be hard to recognize the true floating aid from the surrounding debris in the search for more precise decision-making. Proposed markers include microsatellite instability (MSI), KRAS mutations and BRAF mutations, but a number of gene panels and consensus molecular subtypes are proposed for clinical prediction and prognostication as well. While several studies suggest such biomarkers or panels to have a prognostic role in subgroups of patients, a number of studies are reported in heterogeneous groups with in part discordant findings, which again distorts the predictive and prognostic ability of each marker. Lack of homogeneous cohorts, underpowered studies in strict subgroups and challenges in analytical and clinical validity may hamper the progress towards widespread clinical utility. The harvest of prognostic biomarkers in colon cancer has yielded a huge number of candidates for which it is now time to separate the wheat from the chaff.
TNM系统无法准确预测相当一部分患者的疾病复发情况。虽然淋巴结阴性（II期）结肠癌被认为总体预后良好，但据报道，未接受辅助化疗的患者5年癌症特异性生存率为81%-83%。因此，仅依靠淋巴结状态导致了一部分预后不良的II期患者治疗不足。对II期结肠癌新的更好的预后指标的探索提出了几种有望实现更好预后和预测的生物标志物。然而，很少有这样的生物标志物得到广泛的临床应用。对于身处众多新兴生物标志物海洋中的临床医生来说，在寻找更精确决策依据时，可能很难从周围的杂物中识别出真正有用的辅助工具。提出的标志物包括微卫星不稳定性（MSI）、KRAS突变和BRAF突变，但也有一些基因组合和共识分子亚型被提出用于临床预测和预后评估。虽然几项研究表明这些生物标志物或组合在部分患者亚组中具有预后作用，但许多研究是在异质性群体中进行的，部分结果不一致，这再次影响了每个标志物的预测和预后能力。缺乏同质队列、在严格亚组中研究样本量不足以及分析和临床有效性方面的挑战可能会阻碍其广泛临床应用的进展。结肠癌预后生物标志物的研究产生了大量候选标志物，现在是时候去粗取精了。
