Park Jin Sung, Choi Jin Ah, Hyun Da Han, Byeon Chorok, Kwak Sang Gyu, Park Jun Seok, Hong Seonki
Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.
Discov Oncol. 2024 Oct 30;15(1):605. doi: 10.1007/s12672-024-01481-4.
The challenges associated with liquid biopsy of colorectal cancer (CRC) are closely linked to the substantial variations observed in gene expression profiles among patients. This variability complicates the selection of an ideal biomarker for accurate diagnosis. In this report, we propose that employing a combination of miRNAs offers a better change for enhancing the accuracy of CRC diagnosis compared to solely relying on single miRNAs. As an illustrative example, we measured 9 miRNAs from 45 patient samples (comprising 31 CRC cases and 14 healthy controls) via RT-qPCR. We then utilized two methods: (1) LASSO regression for marker ranking and (2) linear discriminant analysis (LDA) to identify the optimal weighted combination of multiple markers. Our data indicates that combination of triple markers, selected based on their ranking, exhibited the highest diagnostic performance, including a sensitivity of 93.6% (95% confidence interval, CI 79.3-98.9%), specificity of 100% (CI 78.5-100.0%), positive predictive value (PPV) of 100%, negative predictive value (NPV) of 87.5%, and an overall accuracy of 95.6%. In contrast, the diagnostic performance of each individual miRNA used in the triple marker combination ranged from 53.3 to 80.0% in accuracy. While we acknowledge the need for further extensive studies involving larger patient cohorts and the consideration of additional miRNA candidates, our research undeniably highlights the potential of combining multiple markers as a robust methodology for identifying biomarkers among heterogeneous patient profiles.
与结直肠癌（CRC）液体活检相关的挑战与患者基因表达谱中观察到的显著差异密切相关。这种变异性使得选择用于准确诊断的理想生物标志物变得复杂。在本报告中，我们提出，与仅依靠单个miRNA相比，采用miRNA组合能更好地提高CRC诊断的准确性。作为一个示例，我们通过RT-qPCR对45份患者样本（包括31例CRC病例和14例健康对照）中的9种miRNA进行了测量。然后我们使用了两种方法：（1）lasso回归进行标志物排序，（2）线性判别分析（LDA）来识别多个标志物的最佳加权组合。我们的数据表明，根据排名选择的三联标志物组合表现出最高的诊断性能，包括灵敏度为93.6%（95%置信区间，CI 79.3 - 98.9%），特异性为100%（CI 78.5 - 100.0%），阳性预测值（PPV）为100%，阴性预测值（NPV）为87.5%，总体准确率为95.6%。相比之下，三联标志物组合中使用的每种单个miRNA的诊断准确率在53.3%至80.0%之间。虽然我们认识到需要进一步开展涉及更大患者队列的广泛研究，并考虑更多miRNA候选物，但我们的研究无疑凸显了组合多个标志物作为一种强大方法在异质性患者群体中识别生物标志物的潜力。
