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© 2023. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Objective

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.

Methods

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.

Results

The most prevalent driver mutations were BRAF mutations (24.2%), followed by NRAS (15.2%), KIT (12.1%), KRAS (9.1%) and NF1 (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 (CDKNA2 loss, MDM2 gain/amplification and TP53 mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months vs. 3.9 months, P = 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, GZMH, GZMK, AIM2 and CTLA4, were found to be associated with both PFS and OS.

Conclusion

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.

Details

Title
Genomic and tumour microenvironmental biomarkers of immune checkpoint inhibitor response in advanced Taiwanese melanoma
Author
John Wen-Cheng Chang 1 ; Chien-Jung, Huang 2 ; Wen-Kuan, Huang 1 ; Yu-Chao, Wang 2 ; Jia-Juan Hsieh 1 ; Yao-Yu, Chang 3 ; Yen-Lin, Huang 4 ; Wu, Chia-Ling 5 ; Yeh-Han, Wang 5 ; Chen, Shu-Jen 5 ; Kien Thiam Tan 6 ; Chiao-Ping, Chen 1   VIAFID ORCID Logo  ; Wu, Chiao-En 1   VIAFID ORCID Logo 

 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 
 Department of Dermatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan 
 School of Medicine, National Tsing-Hua University, Hsinchu, Taiwan; Department of Anatomic Pathology, Chang Gung Memorial Hospital at Linkou, Institute of Stem Cell and Translational Cancer Research, Taoyuan, Taiwan 
 ACT Genomics Co., Ltd, Taipei, Taiwan 
 ACT Genomics Co., Ltd, Taipei, Taiwan; Anbogen Therapeutics Co., Ltd, Taipei, Taiwan 
Section
Original Article
Publication year
2023
Publication date
2023
Publisher
John Wiley & Sons, Inc.
e-ISSN
20500068
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2858215487
Copyright
© 2023. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.