靶向治疗和免疫治疗在非小细胞肺癌（NSCLC）的治疗中都很重要。准确诊断和精准治疗是实现患者长期生存的关键。 MET 融合是一种罕见的致癌因素，其最佳检测和治疗方法尚未确定。在此，我们报道了一名 32 岁女性肺腺癌患者，通过基于 DNA 的下一代测序 (NGS) 检测出 PD-L1 呈阳性且驱动基因呈阴性。化疗后原发灶根治性切除联合PD-1检查点抑制剂给药，根据她的病理反应和快速复发，表明原发性免疫抵抗。基于RNA的NGS检测到了罕见的CD47-MET，并通过荧光原位杂交证实了这一点。多重免疫荧光显示 PD-L1 相关的异质免疫抑制微环境，CD4 T 细胞和 CD8 T 细胞分布很少。沃利替尼治疗导致无进展生存期 (PFS) > 12 个月，直到疾病进展后通过重新活检和基于 DNA-RNA 的联合 NGS 检测到 MET p.D1228H 中新的继发耐药突变。本例中，CD47-MET融合NSCLC主要对免疫治疗耐药，对沃利替尼敏感，并在靶向治疗后出现继发性MET p.D1228H突变。基于 DNA-RNA 的 NGS 可用于检测此类分子事件和追踪耐药性的二次突变。为此，基于 DNA-RNA 的 NGS 在指导该患者群体的精准诊断和个体化治疗方面可能具有更好的价值。版权所有 © 2024 Wang、Liu、Yu、Wang 和 Liu。

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. MET fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare CD47-MET was detected by RNA-based NGS, which was confirmed by fluorescence in situ hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, CD47-MET fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary MET p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.Copyright © 2024 Wang, Liu, Yu, Wang and Liu.