Fung Kim Y C, Tabor Bruce, Buckley Michael J, Priebe Ilka K, Purins Leanne, Pompeia Celine, Brierley Gemma V, Lockett Trevor, Gibbs Peter, Tie Jeanne, McMurrick Paul, Moore James, Ruszkiewicz Andrew, Nice Edouard, Adams Timothy E, Burgess Antony, Cosgrove Leah J
CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
Royal Melbourne Hospital, Melbourne, Victoria, Australia.
PLoS One. 2015 Mar 20;10(3):e0120425. doi: 10.1371/journal.pone.0120425. eCollection 2015.
The majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second most common internal cancer in Australia, only 30 per cent of the population considered to have risk factors participate in stool-based test screening programs. Evidence indicates a robust, blood-based, diagnostic assay would increase screening compliance. A number of potential diagnostic blood-based protein biomarkers for CRC have been reported, but all lack sensitivity or specificity for use as a stand-alone diagnostic. The aim of this study was to identify and validate a panel of protein-based biomarkers in independent cohorts that could be translated to a reliable, non-invasive blood-based screening test.
In two independent cohorts (n = 145 and n = 197), we evaluated seven single biomarkers in serum of CRC patients and age/gender matched controls that showed a significant difference between controls and CRC, but individually lack the sensitivity for diagnostic application. Using logistic regression strategies, we identified a panel of three biomarkers that discriminated between controls and CRC with 73% sensitivity at 95% specificity, when applied to either of the two cohorts. This panel comprised of Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2).
Due to the heterogeneous nature of CRC, a single biomarker is unlikely to have sufficient sensitivity or specificity for use as a stand-alone diagnostic screening test and a panel of markers may be more effective. We have identified a 3 biomarker panel that has higher sensitivity and specificity for early stage (Stage I and -II) disease than the faecal occult blood test, raising the possibility for its use as a non-invasive blood diagnostic or screening test.
大多数结直肠癌（CRC）病例可通过早期发现和切除癌前息肉来预防。尽管CRC是澳大利亚第二常见的内部癌症，但在被认为有风险因素的人群中，只有30%参与了基于粪便检测的筛查项目。有证据表明，一种强大的、基于血液的诊断检测方法将提高筛查的依从性。已经报道了许多潜在的用于CRC的基于血液诊断的蛋白质生物标志物，但所有这些标志物作为独立诊断工具时都缺乏敏感性或特异性。本研究的目的是在独立队列中识别和验证一组基于蛋白质的生物标志物，这些标志物可转化为一种可靠的、非侵入性的基于血液的筛查检测方法。
在两个独立队列（n = 145和n = 197）中，我们评估了CRC患者血清中的七种单一生物标志物以及年龄/性别匹配的对照组，这些生物标志物在对照组和CRC患者之间显示出显著差异，但单独使用时缺乏诊断应用所需的敏感性。使用逻辑回归策略，我们确定了一组由三种生物标志物组成的标志物组合，当应用于两个队列中的任何一个时，该组合在95%特异性下对对照组和CRC的区分敏感性为73%。该组合由胰岛素样生长因子结合蛋白2（IGFBP2）、Dickkopf-3（DKK3）和丙酮酸激酶M2（PKM2）组成。
由于CRC的异质性，单一生物标志物不太可能具有足够的敏感性或特异性用于独立的诊断筛查检测，而一组标志物可能更有效。我们已经确定了一个由三种生物标志物组成的组合，其对早期（I期和II期）疾病的敏感性和特异性高于粪便潜血试验，这增加了将其用作非侵入性血液诊断或筛查检测的可能性。
