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Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2023 Vol.24 No.2 P.143-156
USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer
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.
Key words: Immune checkpoint inhibitor (ICI); Lung cancer; Usher syndrome type-2A (USH2A) missense mutation; Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation; Epidermal growth factor receptor (EGFR) mutation
机构：1武汉科技大学，机器人与智能系统研究所，中国武汉，430081；2武汉科技大学，冶金设备与控制技术教育部重点实验室，中国武汉，430081
目的：Savonius型垂直轴风力机具有较好的自启动性能和较低的制造成本。然而，较低的风能利用效率制约其进一步发展。因此，本文将附加圆柱引入风力机叶片设计中，利用附加圆柱产生的涡流来控制风力机叶片周围的流体流动，以提高Savonius风力机的捕能效率。
创新点：1.将附加圆柱引入Savonius风力机的叶片设计中，提高传统Savonius风力机的捕能效率；2.构建一种动力学形式的数学模型，用于有效求解风致Savonius风力机的转动过程。
方法：1.通过理论推导，构建一种动力学形式的数学模型，用于有效求解风致Savonius风力机的转动过程（公式(S3)）；2.通过田口实验优化，研究附加圆柱Savonius风力机的3个特征参数对其捕能性能的影响，得到各因素的影响权重排序（图4）；3.通过仿真模拟，找到附加圆柱Savonius风力机捕能效率提高的主要原因（图7和8）；4.通过实验设计，证明附加圆柱对提升Savonius风力机捕能效率的积极影响，同时也验证数值模型的正确性（图10）。
结论：1.附加圆柱可有效改善Savonius风力机的气动性能；当α=45°，D=10mm，r=20mm时，与常规Savonius风力机相比，附加圆柱的Savonius风力机的平均转矩系数和平均功率系数分别提高了7%和15%。2.附加圆柱Savonius风力机的3个特征参数对平均功率系数的影响排序为D>α>r。3.附加圆柱Savonius风力机捕能效率更高的主要原因是附加圆柱加快了返回叶片凹面上涡流的脱落速度，进而导致叶片两侧产生较大的压力差。4.实验结果表明，附加圆柱Savonius风力机的输出功率比传统Savonius风力机提高了29%，与仿真结果一致。
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DOI:
10.1631/jzus.B2200292
CLC number:
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On-line Access:
2023-02-05
Received:
2022-05-20
Revision Accepted:
2022-10-08
Crosschecked:
2023-02-09