RESUMEN
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 KRASG12Cmutation 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.
Asunto(s)
Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Proteínas de la Matriz Extracelular/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Resultado del TratamientoRESUMEN
T-box transcription factor gene (TBX) interferes with the origin and development of organs, and TBX5 is expressed highest in normal cardiac and pulmonary tissues. Lack of TBX5 may lead to thoracic malformation and abnormal diaphragmatic development, in which ectopic expression and overexpression may induce the apoptosis of cell and inhibit the development of cell. Previous studies demonstrated the potential role of TBX5 in the development and progression of esophageal adenocarcinoma, gastric cancer, colon cancer and breast cancer. We reviewed the association between the expression of TBX2 subfamily and the prognosis, and explore the research progress of TBX5 in regulating the development and progression of lung cancer. Even though the relationshihp the development of lung cancer and TBX5 are not clear, TBX5 could significantly inhibit in vivo tumor growth, and the level of TBX5 was negatively correlated with lung cancer progression. Therefore, the gene expression levels and methylation extent of TBX could be a potential biomarker to reveal the proliferation and metastasis of lung cancer, as well as a therapeutic target for lung cancer. .