Full Text:
<1321>
Summary: 
<611>
Suppl. Mater.: 
CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2023-02-09
Cited: 0
Clicked: 1536
Citations: Bibtex RefMan EndNote GB/T7714
USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer
| ||||||||||||||
Dexin YANG, Yuqin FENG, Haohua LU, Kelie CHEN, Jinming XU, Peiwei LI, Tianru WANG, Dajing XIA, Yihua WU. USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer[J]. Journal of Zhejiang University Science B, 2023, 24(2): 143-156.
@article{title="USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer",
author="Dexin YANG, Yuqin FENG, Haohua LU, Kelie CHEN, Jinming XU, Peiwei LI, Tianru WANG, Dajing XIA, Yihua WU",
journal="Journal of Zhejiang University Science B",
volume="24",
number="2",
pages="143-156",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200292"
}
%0 Journal Article
%T USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer
%A Dexin YANG
%A Yuqin FENG
%A Haohua LU
%A Kelie CHEN
%A Jinming XU
%A Peiwei LI
%A Tianru WANG
%A Dajing XIA
%A Yihua WU
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 2
%P 143-156
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200292
TY - JOUR
T1 - USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer
A1 - Dexin YANG
A1 - Yuqin FENG
A1 - Haohua LU
A1 - Kelie CHEN
A1 - Jinming XU
A1 - Peiwei LI
A1 - Tianru WANG
A1 - Dajing XIA
A1 - Yihua WU
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 2
SP - 143
EP - 156
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200292
Abstract: This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‒1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‒2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‒1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‒1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A (USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‒0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‒0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‒8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‒6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12C mutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
[1]Abou AlaiwiS, NassarAH, XieWL, et al., 2020. Mammalian SWI/SNF complex genomic alterations and immune checkpoint blockade in solid tumors. Cancer Immunol Res, 8(8):1075-1084.
[2]AddeoA, BannaGL, WeissGJ, 2019. Tumor mutation burden—from hopes to doubts. JAMA Oncol, 5(7):934-935.
[3]AnagnostouV, NiknafsN, MarroneK, et al., 2020. Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer. Nat Cancer, 1(1):99-111.
[4]ArbourKC, RizviH, PlodkowskiAJ, et al., 2021. Treatment outcomes and clinical characteristics of patients with KRAS-G12C-mutant non-small cell lung cancer. Clin Cancer Res, 27(8):2209-2215.
[5]AssounS, Theou-AntonN, NguenangM, et al., 2019. Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer. Lung Cancer, 132:65-71.
[6]BenthamR, LitchfieldK, WatkinsTBK, et al., 2021. Using DNA sequencing data to quantify T cell fraction and therapy response. Nature, 597(7877):555-560.
[7]BrahmerJR, 2013. Harnessing the immune system for the treatment of non-small-cell lung cancer. J Clin Oncol, 31(8):1021-1028.
[8]CaiWJ, ZhouDP, WuWB, et al., 2018. MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design. BMC Genomics, 19:582.
[9]CanonJ, RexK, SaikiAY, et al., 2019. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature, 575(7781):217-223.
[10]ChoJW, ParkS, KimG, et al., 2021. Dysregulation of TFH-B-TRM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer. Nat Commun, 12:6068.
[11]DongZY, ZhongWZ, ZhangXC, et al., 2017. Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clin Cancer Res, 23(12):3012-3024.
[12]EisenhauerEA, TherasseP, BogaertsJ, et al., 2009. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 45(2):228-247.
[13]EudyJD, WestonMD, YaoSF, et al., 1998. Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. Science, 280(5370):1753-1757.
[14]FangWF, MaYX, YinJC, et al., 2019. Comprehensive genomic profiling identifies novel genetic predictors of response to anti-PD-(L)1 therapies in non-small cell lung cancer. Clin Cancer Res, 25(16):5015-5026.
[15]FangWF, JinHX, ZhouHQ, et al., 2021. Intratumoral heterogeneity as a predictive biomarker in anti-PD-(L)1 therapies for non-small cell lung cancer. Mol Cancer, 20:37.
[16]FrigolaJ, NavarroA, CarbonellC, et al., 2021. Molecular profiling of long-term responders to immune checkpoint inhibitors in advanced non-small cell lung cancer. Mol Oncol, 15(4):887-900.
[17]GainorJF, ShawAT, SequistLV, et al., 2016. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin Cancer Res, 22(18):4585-4593.
[18]GandaraDR, PaulSM, KowanetzM, et al., 2018. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med, 24(9):1441-1448.
[19]GaoG, LiaoWT, MaQZ, et al., 2020. KRAS G12D mutation predicts lower TMB and drives immune suppression in lung adenocarcinoma. Lung Cancer, 149:41-45.
[20]GuZG, EilsR, SchlesnerM, 2016. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics, 32(18):2847-2849.
[21]GaoZR, LingXY, ShiCY, et al., 2022. Tumor immune checkpoints and their associated inhibitors. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(10):823-843.
[22]HastingsK, YuHA, WeiW, et al., 2019. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer. Ann Oncol, 30(8):1311-1320.
[23]HataA, KatakamiN, NanjoS, et al., 2017. Programmed death-ligand 1 expression and T790M status in EGFR-mutant non-small cell lung cancer. Lung Cancer, 111:182-189.
[24]HellmannMD, NathansonT, RizviH, et al., 2018. Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell, 33(5):843-852.e4.
[25]JeansonA, TomasiniP, Souquet-BressandM, et al., 2019. Efficacy of immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer (NSCLC). J Thorac Oncol, 14(6):1095-1101.
[26]JiaQZ, WangJ, HeN, et al., 2019. Titin mutation associated with responsiveness to checkpoint blockades in solid tumors. JCI Insight, 4(10):e127901.
[27]JiaQZ, ChiuL, WuSX, et al., 2020. Tracking neoantigens by personalized circulating tumor DNA sequencing during checkpoint blockade immunotherapy in non-small cell lung cancer. Adv Sci (Weinh), 7(9):1903410.
[28]KumagaiS, KoyamaS, NishikawaH, 2021. Antitumour immunity regulated by aberrant ERBB family signalling. Nat Rev Cancer, 21(3):181-197.
[29]LeeCK, ManJ, LordS, et al., 2017. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung cancer—a meta-analysis. J Thorac Oncol, 12(2):403-407.
[30]LiuCM, ZhengSF, JinRS, et al., 2020. The superior efficacy of anti-PD-1/PD-L1 immunotherapy in KRAS-mutant non-small cell lung cancer that correlates with an inflammatory phenotype and increased immunogenicity. Cancer Lett, 470:95-105.
[31]MazieresJ, DrilonA, LusqueA, et al., 2019. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol, 30(8):1321-1328.
[32]MiaoDN, MargolisCA, VokesNI, et al., 2018. Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet, 50(9):1271-1281.
[33]ModingEJ, LiuYF, NabetBY, et al., 2020. Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small-cell lung cancer. Nat Cancer, 1(2):176-183.
[34]OscanoaJ, SivapalanL, GadaletaE, et al., 2020. SNPnexus: a web server for functional annotation of human genome sequence variation (2020 update). Nucleic Acids Res, 48(W1):W185-W192.
[35]PenderA, TitmussE, PleasanceED, et al., 2021. Genome and transcriptome biomarkers of response to immune checkpoint inhibitors in advanced solid tumors. Clin Cancer Res, 27(1):202-212.
[36]PengDJ, KryczekI, NagarshethN, et al., 2015. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature, 527(7577):249-253.
[37]ReussJE, AnagnostouV, CottrellTR, et al., 2020. Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer. J Immunother Cancer, 8(2):e001282.
[38]RivoltaC, BersonEL, DryjaTP, 2002. Paternal uniparental heterodisomy with partial isodisomy of chromosome 1 in a patient with retinitis pigmentosa without hearing loss and a missense mutation in the Usher syndrome type II gene USH2A. Arch Ophthalmol, 120(11):1566-1571.
[39]RizviH, Sanchez-VegaF, LaK, et al., 2018. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol, 36(7):633-641.
[40]RizviNA, HellmannMD, SnyderA, et al., 2015. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 348(6230):124-128.
[41]SabapathyK, LaneDP, 2018. Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others. Nat Rev Clin Oncol, 15(1):13-30.
[42]SamsteinRM, LeeCH, ShoushtariAN, et al., 2019. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet, 51(2):202-206.
[43]SequistLV, WaltmanBA, Dias-SantagataD, et al., 2011. Genotypic and histological evolution of lung cancers acquiring resistance to egfr inhibitors. Sci Transl Med, 3(75):75ra26.
[44]StevenA, FisherSA, RobinsonBW, 2016. Immunotherapy for lung cancer. Respirology, 21(5):821-833.
[45]SugiyamaE, TogashiY, TakeuchiY, et al., 2020. Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer. Sci Immunol, 5(43):eaav3937.
[46]SunH, LiuSY, ZhouJY, et al., 2020. Specific TP53 subtype as biomarker for immune checkpoint inhibitors in lung adenocarcinoma. EBioMedicine, 60:102990.
[47]SunYY, LiL, YaoWC, et al., 2021. USH2A mutation is associated with tumor mutation burden and antitumor immunity in patients with colon adenocarcinoma. Front Genet, 12:762160.
[48]SzolekA, SchubertB, MohrC, et al., 2014. OptiType: precision HLA typing from next-generation sequencing data. Bioinformatics, 30(23):3310-3316.
[49]TalevichE, ShainAH, BottonT, et al., 2016. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput Biol, 12(4):e1004873.
[50]ToualbiL, TomsM, MoosajeeM, 2020. USH2A-retinopathy: from genetics to therapeutics. Exp Eye Res, 201:108330.
[51]TsaoMS, KerrKM, KockxM, et al., 2018. PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol, 13(9):1302-1311.
[52]WestonMD, EudyJD, FujitaS, et al., 2000. Genomic structure and identification of novel mutations in Usherin, the gene responsible for Usher syndrome type IIa. Am J Hum Genet, 66(4):1199-1210.
[53]WuSG, ShihJY, 2018. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer, 17:38.
[54]YarchoanM, HopkinsA, JaffeeEM, 2017. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med, 377(25):2500-2501.
[55]YuHA, ArcilaME, RekhtmanN, et al., 2013. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res, 19(8):2240-2247.
[56]YuYF, LinDG, LiAL, et al., 2020. Association of immune checkpoint inhibitor therapy with survival in patients with cancers with MUC16 variants. JAMA Netw Open, 3(6):e205837.
[57]ZhangL, HanXH, ShiYK, 2020. Association of MUC16 mutation with response to immune checkpoint inhibitors in solid tumors. JAMA Netw Open, 3(8):e2013201.
[58]ZhuGS, RenD, LeiX, et al., 2021. Mutations associated with no durable clinical benefit to immune checkpoint blockade in non-s-cell lung cancer. Cancers (Basel), 13(6):1397.
ORCID: 
Open peer comments: Debate/Discuss/Question/Opinion
<1>