Chang John Wen-Cheng, Huang Chien-Jung, Huang Wen-Kuan, Wang Yu-Chao, Hsieh Jia-Juan, Chang Yao-Yu, Huang Yen-Lin, Wu Chia-Ling, Wang Yeh-Han, Chen Shu-Jen, Tan Kien Thiam, Chen Chiao-Ping, Wu Chiao-En
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine Chang Gung University Taoyuan Taiwan.
Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taipei Taiwan.
Clin Transl Immunology. 2023 Aug 29;12(8):e1465. doi: 10.1002/cti2.1465. eCollection 2023.
Genomic biomarkers predicting immune checkpoint inhibitor (ICI) treatment outcomes for Asian metastatic melanoma have been rarely reported. This study presents data on next-generation sequencing (NGS) and tumour microenvironment biomarkers in 33 cases.
Thirty-three patients with advanced melanoma, who underwent ICI treatment at the Chang Gung Memorial Hospital in Taiwan, were recruited. The study evaluated clinical outcomes, including response rate, disease control rate, progression-free survival (PFS) rate and overall survival (OS) rate. Archived tissue samples from 33 cases were subjected to NGS by ACTOnco, and ACTTME was employed in 25 cases.
The most prevalent driver mutations were mutations (24.2%), followed by (15.2%), (12.1%), (9.1%) and (9.1%) mutations. Acral/mucosal melanomas exhibited distinct mutation patterns compared to non-acral melanomas. Tumour mutational burden estimated using ACTOnco was not associated with ICI efficacy. Notably, genetic alterations in the p53 pathway ( loss, gain/amplification and mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months 3.9 months, 0.0394). Moreover, 26 genes were identified as differentially expressed genes that were upregulated in patients with clinical benefits compared to those without benefits. Four genes, , , and , were found to be associated with both PFS and OS.
Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings.
预测亚洲转移性黑色素瘤免疫检查点抑制剂（ICI）治疗结果的基因组生物标志物鲜有报道。本研究展示了33例患者的二代测序（NGS）和肿瘤微环境生物标志物数据。
招募了33例在台湾长庚纪念医院接受ICI治疗的晚期黑色素瘤患者。该研究评估了临床结果，包括缓解率、疾病控制率、无进展生存期（PFS）率和总生存期（OS）率。33例患者的存档组织样本由ACTOnco进行NGS检测，25例患者采用ACTTME检测。
最常见的驱动基因突变是 突变（24.2%），其次是 （15.2%）、 （12.1%）、 （9.1%）和 （9.1%）突变。肢端/黏膜黑色素瘤与非肢端黑色素瘤相比表现出不同的突变模式。使用ACTOnco估算的肿瘤突变负荷与ICI疗效无关。值得注意的是，p53通路中的基因改变（ 缺失、 获得/扩增和 突变）占36.4%，并且与不良的PFS显著相关（中位PFS 2.7个月对3.9个月， =0.0394）。此外，26个基因被鉴定为差异表达基因，与无临床获益的患者相比，这些基因在有临床获益的患者中上调。发现4个基因 、 、 和 与PFS和OS均相关。
p53通路中的基因改变可能对接受ICI治疗的亚洲黑色素瘤患者至关重要。需要进一步研究以探索这一机制并验证这些发现。
