A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk.
A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk.
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DOI：
10.1038/s41598-021-83968-6
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发表时间：
2021-03-04
影响因子：
4.6
通讯作者：
Van Guelpen B
中科院分区：
文献类型：
--
作者：
Harlid S;Harbs J;Myte R;Brunius C;Gunter MJ;Palmqvist R;Liu X;Van Guelpen B
结直肠癌的预后取决于分期，迫切需要采取措施改善早期发现。使用前瞻性收集的血浆样本，从人口为基础的北方瑞典健康和疾病研究，我们评估蛋白质生物标志物与结直肠癌的风险。应用两层的方法，我们分析了160个蛋白质匹配的连续样本从58个事件的结直肠癌病例对照对。然后在450个病例对照对的验证集中分析了从发现阶段和文献中选择的21种蛋白质。采用条件Logistic回归分析估计比值比。多指标分析采用LASSO回归和ROC分析。在主要验证分析中，无蛋白质保持统计学显著性。然而，探索性亚组分析显示FGF-21与结肠癌风险之间存在相关性（多变量OR/1 SD：1.23 95% CI 1.03-1.47），PPY与直肠癌风险之间也存在相关性（多变量OR/1 SD：1.47 95% CI 1.12-1.92）。在基本风险预测模型中添加蛋白质标记物适度提高了性能。我们的研究结果强调了开发生物标志物的挑战，这些生物标志物在早期发现结直肠癌的无症状、诊断前的机会窗口中有效。区分癌症亚型可以提高预测准确性。然而，单一的生物标志物或小组可能不足以进行有效的精确筛选。
Colorectal cancer prognosis is dependent on stage, and measures to improve early detection are urgently needed. Using prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study, we evaluated protein biomarkers in relation to colorectal cancer risk. Applying a two-tiered approach, we analyzed 160 proteins in matched sequential samples from 58 incident colorectal cancer case–control pairs. Twenty-one proteins selected from both this discovery phase and the literature were then analyzed in a validation set of 450 case–control pairs. Odds ratios were estimated by conditional logistic regression. LASSO regression and ROC analysis were used for multi-marker analyses. In the main validation analysis, no proteins retained statistical significance. However, exploratory subgroup analyses showed associations between FGF-21 and colon cancer risk (multivariable OR per 1 SD: 1.23 95% CI 1.03–1.47) as well as between PPY and rectal cancer risk (multivariable OR per 1 SD: 1.47 95% CI 1.12–1.92). Adding protein markers to basic risk predictive models increased performance modestly. Our results highlight the challenge of developing biomarkers that are effective in the asymptomatic, prediagnostic window of opportunity for early detection of colorectal cancer. Distinguishing between cancer subtypes may improve prediction accuracy. However, single biomarkers or small panels may not be sufficient for effective precision screening.
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影响因子：
24.5
作者：
Smith T;Muller DC;Moons KGM;Cross AJ;Johansson M;Ferrari P;Fagherazzi G;Peeters PHM;Severi G;Hüsing A;Kaaks R;Tjonneland A;Olsen A;Overvad K;Bonet C;Rodriguez-Barranco M;Huerta JM;Barricarte Gurrea A;Bradbury KE;Trichopoulou A;Bamia C;Orfanos P;Palli D;Pala V;Vineis P;Bueno-de-Mesquita B;Ohlsson B;Harlid S;Van Guelpen B;Skeie G;Weiderpass E;Jenab M;Murphy N;Riboli E;Gunter MJ;Aleksandrova KJ;Tzoulaki I
通讯作者：
Tzoulaki I
影响因子：
24.5
作者：
Rho JH;Ladd JJ;Li CI;Potter JD;Zhang Y;Shelley D;Shibata D;Coppola D;Yamada H;Toyoda H;Tada T;Kumada T;Brenner DE;Hanash SM;Lampe PD
通讯作者：
Lampe PD
影响因子：
6.6
作者：
Bhardwaj, Megha;Weigl, Korbinian;Brenner, Hermann
通讯作者：
Brenner, Hermann
血浆间皮素作为结直肠癌的新型诊断和预后生物标志物
影响因子：
3.9
作者：
Li S;Xie L;He L;Fan Z;Xu J;Xu K;Zhu L;Ma G;Du M;Chu H;Zhang Z;Ni M;Wang M
通讯作者：
Wang M
影响因子：
2.6
作者：
Norberg M;Wall S;Boman K;Weinehall L
通讯作者：
Weinehall L