Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA, USA.
Department of Surgery, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.
Br J Cancer. 2021 Sep;125(6):846-853. doi: 10.1038/s41416-021-01461-3. Epub 2021 Jun 23.
Delayed detection of tumours contributes to poor prognosis in patients with gastric cancer (GC). The invasive nature of endoscopy and the absence of an effective serum markers highlight the need to develop novel, noninvasive biomarkers.
We performed biomarker discovery and validation to identify candidate genes in three gene expression data sets. After validating the gene panel in clinical tissues, we translated the gene panel into serum samples by performing training and validation in 89 samples from GC patients and 54 from healthy donors in two independent cohorts.
We identified a nine-gene panel in the discovery phase, with subsequent validation in tissue specimens. Using a serum training cohort, we developed a 5-gene risk prediction formulae for the diagnosis of GC; bootstrapped analysis exhibited an AUC of 0.896. We validated this 5-gene biomarker panel using an independent serum cohort, yielding an AUC of 0.947. This biomarker panel successfully identified GC, regardless of tumour histology. Notably, biomarker performance for detection of stage 1 and 2 GC displayed an AUC of 0.928 and 0.980 in both serum cohorts.
We identified a novel 5-gene biomarker panel for noninvasive diagnosis of GC, which might serve as a potential diagnostic tool for early detection.
胃癌（GC）患者肿瘤的延迟检测导致预后不良。内窥镜检查的侵入性和缺乏有效的血清标志物突出表明需要开发新型的非侵入性生物标志物。
我们在三个基因表达数据集上进行了生物标志物的发现和验证，以鉴定候选基因。在临床组织中验证了基因表达谱后，我们通过在 89 名 GC 患者和 54 名健康供体的两个独立队列中进行训练和验证，将基因表达谱转化为血清样本。
我们在发现阶段确定了一个由九个基因组成的基因表达谱，随后在组织标本中进行了验证。使用血清训练队列，我们开发了一种用于 GC 诊断的 5 个基因风险预测公式；自举分析显示 AUC 为 0.896。我们使用独立的血清队列验证了这个 5 个基因的生物标志物谱，AUC 为 0.947。该生物标志物谱成功地识别了 GC，而与肿瘤组织学无关。值得注意的是，该生物标志物谱在两个血清队列中检测 1 期和 2 期 GC 的性能，AUC 分别为 0.928 和 0.980。
我们确定了一个用于 GC 非侵入性诊断的新型 5 个基因生物标志物谱，它可能成为早期检测的潜在诊断工具。
