Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.
Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore.
BMC Cancer. 2023 Feb 3;23(1):118. doi: 10.1186/s12885-022-10444-3.
Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).
Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.
Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.
DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.
传统的差异表达（DE）检测比较肿瘤样本的分组平均值与正常样本的分组平均值，可能会遗漏小部分患者亚群中失调的基因。对于像肝细胞癌（HCC）这样高度异质的癌症尤其如此。
使用 90 名患者的多区域采样 RNA-seq 数据，我们对患者进行了特定于患者的差异表达检测，同时还检测了患者匹配的相邻正常样本。
通过比较传统 DE 分析和患者特异性 DE 分析的结果，我们发现由于肿瘤和正常组织中存在的个体间高度变异性，常规 DE 分析会遗漏一些基因。在小部分患者中共享的失调基因可用于对患者进行分层，并且呈现出不同的预后。我们还表明，一些目前用于 HCC 的靶向药物的靶基因表现出高度个体化的失调模式，这可能解释了反应率低的原因。
讨论/结论：我们的结果强调了鉴定患者特异性 DE 基因的重要性，这可能为精准医学中的患者亚组提供有临床价值的见解。
