A novel risk model of three gefitinib-related genes FBP1, SBK1 and AURKA is related to the immune microenvironment and is predicting prognosis of lung adenocarcinoma patients.

PURPOSE: Gefitinib, an anticancer drug, has been reported to potentially improve the prognosis of patients with lung adenocarcinoma (LUAD). This study aims to investigate the roles and mechanisms of Gefitinib. METHODS: The effects of Gefitinib on the growth and migration of LUAD cells were assessed using various methods, including CCK-8, flow cytometry, wound healing, and Transwell assays. To analyze the function and mechanisms of the differentially expressed Gefitinib target genes (GTGs), data from the TCGA database were utilized. Kaplan-Meier survival and ROC analysis identified prognostic-related GTGs and constructed a prognostic nomogram in LUAD. Consensus clustering, COX analysis and survival analysis evaluated the relationship between GTGs and the prognosis of LUAD patients. The mechanisms of the risk model involved LUAD progression, and the relationship between the risk model and immune microenvironment were investigated. RESULTS: Gefitinib could inhibit proliferation, migration and invasion and promote cell apoptosis. 84 DEGTGs were involved in RAS, MAPK, ERBB pathways. The DEGTGs (FBP1, SBK1, and AURKA) were the independent risk factors for dismal prognosis of LUAD patients and were used to establish risk model and nomogram. Gefitinib could promote the expression of FBP1 and inhibit the expression of SBK1 and AURKA. High-risk LUAD patients had the dismal prognosis, and the high-risk score group was significantly associated with the immune microenvironment. CONCLUSION: FBP1, SBK1, and AURKA are prognostic risk factors, and the risk model and nomogram of FBP1, SBK1 and AURKA are associated with dismal prognosis and immune cell infiltration, and have huge prospects for application in evaluating the prognosis in LUAD.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

OBJECTIVE: The combination of stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitors (ICIs) is actively being explored in advanced non-small-cell lung cancer (NSCLC) patients. However, little is known about the optimal fractionation and radiotherapy target lesions in this scenario. This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs. METHODS: The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec. 2015 to Sep. 2021. Patients were grouped according to radiation sites. Progression-free survival (PFS) and overall survival (OS) were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank (Mantel-Cox) test. RESULTS: A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study. Radiation sites included lung lesions (lung group, n=43), bone metastases (bone group, n=24), and brain metastases (brain group, n=57). Compared with the brain group, the mean PFS (mPFS) in the lung group was significantly prolonged by 13.3 months (8.5 months vs. 21.8 months, HR=0.51, 95%CI: 0.28-0.92, P=0.0195), and that in the bone group prolonged by 9.5 months with a 43% reduction in the risk of disease progression (8.5 months vs. 18.0 months, HR=0.57, 95%CI: 0.29-1.13, P=0.1095). The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group. The mean OS (mOS) in the lung and bone groups was longer than that of the brain group, and the risk of death decreased by up to 60% in the lung and bone groups as compared with that of the brain group. When SBRT was concurrently given with ICIs, the mPFS in the lung and brain groups were significantly longer than that of the bone group (29.6 months vs. 16.5 months vs. 12.1 months). When SBRT with 8-12 Gy per fraction was combined with ICIs, the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups (25.4 months vs. 15.2 months vs. 12.0 months). Among patients receiving SBRT on lung lesions and brain metastases, the mPFS in the concurrent group was longer than that of the SBRT→ICIs group (29.6 months vs. 11.4 months, P=0.0003 and 12.1 months vs. 8.9 months, P=0.2559). Among patients receiving SBRT with <8 Gy and 8-12 Gy per fraction, the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group (20.1 months vs. 5.3 months, P=0.0033 and 24.0 months vs. 13.4 months, P=0.1311). The disease control rates of the lung, bone, and brain groups were 90.7%, 83.3%, and 70.1%, respectively. CONCLUSION: The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients. This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens. Dose fractionation regimens of 8-12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.