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动态基因筛查有助于识别一个用于胃癌早期检测和病情进展评估的10基因组合。

Dynamic gene screening enabled identification of a 10-gene panel for early detection and progression assessment of gastric cancer.

作者信息

Long Fei, Li Shuo, Xu Yaqi, Liu Min, Zhang Xuan, Zhou Junting, Chen Yiyi, Rong Yuan, Meng Xiangyu, Wang Fubing

机构信息

Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.

Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

Comput Struct Biotechnol J. 2022 Dec 22;21:677-687. doi: 10.1016/j.csbj.2022.12.036. eCollection 2023.

Abstract

Early diagnosis and progression assessment are critical for the timely detection and treatment of gastric cancer (GC) patients. Identification of diagnostic biomarkers for early detection of GC represents an unmet clinical need, and how these markers further influence GC progression is explored rarely. We performed dynamic gene screening based on high-throughput data analysis from patients with precancerous lesions and early gastric cancer (EGC) and identified a 10-gene panel by the lasso regression model. This panel demonstrated good diagnostic performance in TCGA (AUC = 0.95, sensitivity = 86.67 %, specificity = 90.63 %) and GEO (AUC = 0.84, sensitivity = 91.67 %, specificity = 78.13 %) cohorts. Moreover, three GC subtypes were clustered based on this panel, in which cluster 2 (C2) demonstrated the highest tumor progression level with a high expression of 10 genes, showing a decreased tumor mutation burden, significantly enriched epithelial-mesenchymal transition hallmark and increased immune exclusion/exhausted features. Finally, the cell localization of these panel genes was explored in scRNA-seq data based on more than 40,000 cells. The 10-gene panel is expected to be a new clinical early detection signature for GC and may aid in progression assessment and personalized treatment of patients.

摘要

早期诊断和病情进展评估对于胃癌(GC)患者的及时发现和治疗至关重要。识别用于早期检测GC的诊断生物标志物是一项尚未满足的临床需求,而这些标志物如何进一步影响GC进展的研究却很少。我们基于对癌前病变和早期胃癌(EGC)患者的高通量数据分析进行了动态基因筛选,并通过套索回归模型确定了一个包含10个基因的基因panel。该基因panel在TCGA队列(AUC = 0.95,灵敏度 = 86.67%,特异性 = 90.63%)和GEO队列(AUC = 0.84,灵敏度 = 91.67%,特异性 = 78.13%)中表现出良好的诊断性能。此外,基于该基因panel对三种GC亚型进行了聚类,其中聚类2(C2)显示出最高的肿瘤进展水平,10个基因高表达,肿瘤突变负担降低,上皮-间质转化特征显著富集,免疫排斥/耗竭特征增加。最后,基于超过40000个细胞的scRNA-seq数据探索了这些基因panel基因的细胞定位。该包含10个基因的基因panel有望成为GC新的临床早期检测标志物,并可能有助于患者的病情进展评估和个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b5/9826902/5010cadf8d68/ga1.jpg

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