Objective To evaluate the correlation between cyclin B1 (CCNB1) gene expression and the prognosis of lung adenocarcinoma. Methods Oncomine, STRING, Human Protein Atlas, The Cancer Genome Atlas and other databases as well as Kaplan-Meier method, Cox regression, receiver operating characteristic (ROC) curve and Spearman correlation analysis were used to verify the effect of CCNB1 on patients with lung adenocarcinoma. Results CCNB1 was highly expressed in lung adenocarcinoma, and the high expression was correlated with T stage (P=0.001), N stage (P<0.001), pathological stage (P<0.001) and gender (P=0.008). Univariate Cox regression analysis showed that the expression of CCNB1, T stage, N stage, M stage and pathological stage were the factors affecting the overall survival rate of patients with lung adenocarcinoma (P<0.05); multivariate Cox regression analysis showed that the expression of CCNB1 and T stage were independent risk factors for overall survival of patients with lung adenocarcinoma (P<0.05). Kaplan-Meier analysis showed that high expression of CCNB1 was associated with shorter overall survival [hazard ratio (HR)=1.60, 95% confidence interval (CI) (1.20, 2.14), P=0.002], disease-specific survival [HR=1.68, 95%CI (1.16, 2.44), P=0.006] and progression-free interval [HR=1.42, 95%CI (1.09, 1.85), P=0.009]. The ROC curve showed that CCNB1 might be a potential diagnostic molecule for lung adenocarcinoma [area under the curve=0.980, 95%CI (0.967, 0.993)]. Spearman correlation analysis showed that CCNB1 expression was positively correlated with the infiltration of T helper cells 2 (rs=0.805, P<0.001) and T helper cells (rs=0.103, P=0.017), and negatively correlated with the infiltration of natural killer cells (rs=?0.195, P<0.001), macrophages (rs=?0.134, P=0.002), and T cells (rs=?0.092, P=0.033). Conclusion CCNB1 is highly expressed in lung adenocarcinoma compared with normal tissues, which is related to poor prognosis and may provide a potential therapeutic target for patients with lung adenocarcinoma.
Objective To explore the correlation between EZR-ROS1 fusion mutation and acquired resistance to immune checkpoint inhibitors (ICIs) in patients with lung adenocarcinoma, and to provide a reference for clinical diagnosis and treatment after ICIs resistance.MethodsThe clinical data of 1 patient with advanced lung adenocarcinoma who developed acquired resistance after receiving ICIs combined with chemotherapy, was found to have EZR-ROS1 fusion mutation by gene detection, and was treated with entrectinib targeted therapy were reported. Combined with the results of literature retrieval, the related mechanisms of ROS1 fusion mutation-induced ICIs resistance were analyzed.ResultsThe 46-year-old female patient was diagnosed with left lower lobe lung adenocarcinoma (cT3N3M1a, stage IVA). She received first-line pemetrexed + carboplatin + sintilimab chemoimmunotherapy combined with maintenance therapy, and achieved sustained partial response (PR) for about 12 months before disease progression. Second-line docetaxel combined with sintilimab therapy was ineffective. Pelvic lymph node biopsy suggested adenocarcinoma metastasis, immunohistochemistry showed ROS1 protein positivity, and next-generation sequencing (NGS) detected EZR-ROS1 fusion mutation (copy number 6.3%). After third-line entrectinib targeted therapy, the efficacy evaluation was sustained PR for 8 months, then the disease progressed again, and the patient eventually died of lung cancer progression and renal failure. No case reports on the correlation between EZR-ROS1 fusion mutation and ICIs acquired resistance in lung adenocarcinoma were found in the literature retrieval. Only 4 cases of lung adenocarcinoma patients with ROS1 fusion mutation (3 cases were CD74-ROS1 fusion) after chemotherapy or ICIs treatment were retrieved, all of which responded to ROS1 tyrosine kinase inhibitor (TKI) treatment but progressed rapidly. ConclusionsEZR-ROS1 fusion mutation may be a rare driving mechanism of acquired resistance to ICIs in patients with lung adenocarcinoma. When ROS1 fusion mutation is detected after ICIs resistance, timely switching to ROS1-TKI treatment can achieve short-term efficacy, which provides a new idea for clinical individualized diagnosis and treatment after ICIs resistance.