Yao Kenta, Okuno Keisuke, Watanabe Shuichi, Shigeno Takashi, Ogo Taichi, Fujiwara Hisashi, Tanioka Toshiro, Kawada Kenro, Tokunaga Masanori, Ban Daisuke, Kinugasa Yusuke
Department of Gastrointestinal Surgery, Institute of Science Tokyo, Tokyo, Japan.
Department of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Ann Surg Oncol. 2025 May 26. doi: 10.1245/s10434-025-17487-3.
Predicting patients who will benefit from postoperative adjuvant chemotherapy is crucial for precision medicine. Therefore, this study comprehensively analyzed messenger RNA (mRNA) expression profiles to identify novel biomarkers and developed a prediction signature for postoperative adjuvant chemotherapy in patients with gastric cancer (GC).
Biomarkers were discovered by analyzing two publicly available genome-wide datasets from 343 patients with pathologic stages (pStages) II and III GC. A novel prediction signature was developed based on a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay using 137 pStages II and III GC frozen tissue specimens.
Nine novel mRNAs were identified as candidate biomarkers in biomarker discovery, and a Gene Expression-based ADJuvant chemotherapy Response prediction for stages II and III GC (GEx-ADJ-Res) signature was developed using these candidate biomarkers and key clinicopathologic features by qRT-PCR assay. The GEx-ADJ-Res signature robustly predicted postoperative recurrence in clinical tissue samples (area under the curve [AUC], 0.84). The signature demonstrated sufficient potential for predicting response to postoperative adjuvant chemotherapy (AUC, 0.82) and was shown to be an independent predictor of postoperative recurrence and survival in multivariate analysis. Finally, the GEx-ADJ-Res signature was successfully validated using independent multi-institutional datasets (AUC, 0.91, 0.85, and 0.78, respectively).
We identified the novel mRNA biomarkers and developed a novel signature that allowed robust prediction of response to postoperative adjuvant chemotherapy in patients with GC. This signature could become a precision medicine tool in GC treatment.
预测哪些患者将从术后辅助化疗中获益对于精准医学至关重要。因此，本研究全面分析了信使核糖核酸（mRNA）表达谱以识别新的生物标志物，并开发了一种用于胃癌（GC）患者术后辅助化疗的预测特征。
通过分析来自343例病理分期（p分期）为II期和III期GC患者的两个公开可用的全基因组数据集来发现生物标志物。基于定量逆转录聚合酶链反应（qRT-PCR）分析，使用137例p分期为II期和III期GC的冷冻组织标本开发了一种新的预测特征。
在生物标志物发现中，9种新的mRNA被鉴定为候选生物标志物，并通过qRT-PCR分析使用这些候选生物标志物和关键临床病理特征开发了基于基因表达的II期和III期GC辅助化疗反应预测（GEx-ADJ-Res）特征。GEx-ADJ-Res特征在临床组织样本中能有力地预测术后复发（曲线下面积[AUC]，0.84）。该特征在预测术后辅助化疗反应方面显示出足够的潜力（AUC，0.82），并且在多变量分析中被证明是术后复发和生存的独立预测因子。最后，使用独立的多机构数据集成功验证了GEx-ADJ-Res特征（AUC分别为0.91、0.85和0.78）。
我们鉴定了新的mRNA生物标志物并开发了一种新的特征，该特征能够有力地预测GC患者对术后辅助化疗的反应。这一特征可能成为GC治疗中的一种精准医学工具。
