A prognostic signature for lung adenocarcinoma by five genes associated with chemotherapy in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer. Finding prognostic biomarkers is helpful in stratifying LUAD patients with different prognosis. METHODS: We explored the correlation of LUAD prognosis and genes associated with chemotherapy in LUAD and obtained data of LUAD patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Drug sensitivity data were acquired from the Genomics of Drug Sensitivity in Cancer (GDSC) database. Differential and enrichment analyses were used to screen the target genes utilizing limma and "clusterProfiler" packages. Then univariate and LASSO Cox analyses were used to select the prognosis-related genes. Survival analysis was used to estimate the overall survival (OS) of different groups. RESULTS: Twenty-three differentially expressed genes (DEGs) were screened between LUAD samples and healthy samples, and BTK, FGFR2, PIM2, CHEK1, and CDK1 were selected to construct a prognostic signature. The OS of patients in the high-risk group (risk score higher than 0.69) was worse than that in the low-risk group (risk score lower than 0.69). CONCLUSION: The risk score model constructed by five genes is a potential prognostic biomarker for LUAD patients.

Transcriptomic and immunologic implications of the epithelial-mesenchymal transition model reveal a novel role of SFTA2 in prognosis of non-small-cell lung carcinoma.

Non-small-cell lung cancer (NSCLC) is the second most common cancer worldwide, and most deaths are associated with epithelial-mesenchymal transition (EMT). Therefore, this study aimed to explore the role of EMT-related transcriptomic profiles in NSCLC and the effect of EMT-based signatures on clinical diagnosis, prognosis, and treatment responses for patients with NSCLC. After integrating the transcriptomics and clinicopathological data, we first constructed EMT clusters (C1 and C2) using machine learning algorithms, found the significant relationship between EMT clusters and survival outcomes, and then explored the impact of EMT clusters on the tumor heterogeneity, drug efficiency, and immune microenvironment of NSCLC. Prominently, differential-enriched tumor-infiltrated lymphocytes were found between EMT clusters, especially the macrophages and monocyte. Next, we identified the most significantly down-regulated gene SFTA2 in the EMT clusters C2 with poor prognosis. Using RT-qPCR and RNA-seq data from the public database, we found prominently elevated SFTA2 expression in NSCLC tissues compared with normal lung tissues, and the tumor suppressor role of SFTA2 in 82 Chinese patients with NSCLC. After Cox regression and survival analysis, we demonstrated that higher SFTA2 expression in tumor samples significantly predicts favorable prognosis of NSCLC based on multiple independent cohorts. In addition, the prognostic value of SFTA2 expression differs for patients with lung adenocarcinoma and squamous cell carcinoma. In conclusion, this study demonstrated that the EMT process is involved in the malignant progression and the constructed EMT clusters exerted significant predictive drug resistance and prognostic value for NSCLC patients. In addition, we first identified the high tumoral expression of SFTA2 correlated with better prognosis and could serve as a predictive biomarker for outcomes and treatment response of NSCLC patients.

Comparison of Gefitinib in the treatment of patients with non-small cell lung cancer and clinical effects of Osimertinib and EGFR Gene mutation.

Objectives: To compare the clinical effects of Osimertinib and Gefitinib in the treatment of non-small cell lung (NSCLC) complicated with epidermal growth factor receptor (EGFR) gene mutation. Methods: We retrospectively analyzed the clinical data of 102 patients with advanced NSCLC and EGFR gene mutations treated in the Chest Disease Diagnosis and Treatment Center of our hospital from January 2018 to January 2020. We divided the data based on the administered treatments into Osimertinib and Gefitinib groups. The disease control rate (DCR), progression free survival (PFS) and the incidence of adverse events in both groups were analyzed. Results: In the Osimertinib group, there was one patients with complete response (CR), 38 with partial response (PR), eight with stable disease (SD), and two with progressive disease (PD)/ The overall response rate (ORR) was 79.59% (39/49), and the disease control rate (DCR) was 95.92% (47/49). In the Gefitinib group, we found zero patients with CR, 37 patients with PR, 11 with SD, and five with PD. The ORR in the Gefitinib group was 69.80% (37/53) and DCR was 90.57% (48/53). There was no statistical significance between the two groups, ORR was Χ2=0.927 (P=0.336) and the DCR Χ2=0.221 (P=0.638). The median PFS of and Gefitinib groups was significantly higher in the oxitinib group, compared to the Gefitinib group (18.1 months (95% CI 15.4-20.7) and 10.7 months (95% CI 9.9-11.4), respectively, P<0.001). The incidence of adverse reactions in the Osimertinib group was 12.24% (6/49), which was significantly lower than 28.30% (15/53) in the Gefitinib group (P < 0.05). Conclusions: The clinical effect of oxitinib in the treatment of non-small cell lung cancer complicated with EGFR gene mutation is similar to that of Gefitinib. In patients with advanced NSCLC and EGFR gene mutations, oxitinib treatment is associated with significantly longer PFS and lower adverse reaction rate compared with Gefitinib treatment.

A novel SOS1-ALK fusion variant in a patient with metastatic lung adenocarcinoma and a remarkable response to crizotinib.

OBJECTIVES: Transforming anaplastic lymphoma kinase (ALK) gene rearrangements are well known as a unique subset of non-small cell lung cancer (NSCLC) with mutations other than EGFR. Currently, crizotinib is the standard first-line treatment for ALK-positive NSCLC. MATERIALS AND METHODS: With advances in detection methods, more and more uncommon ALK fusion partners have been identified. Herein we present a novel SOS1-ALK fusion and the efficacy of crizotinib in an advanced NSCLC patient harboring this type of fusion. RESULTS: A 52-year-old Chinese man had left upper lobe primary NSCLC and synchronous multiple lung metastases (cT2N3M1, stage IV). The ultrasound-guided fine-needle aspiration cytology of palpable left supraclavicular lymph nodes and the results of immunohistochemistry staining supported the diagnosis of metastatic lung adenocarcinoma. Using a next-generation sequencing assay (NGS), we showed that the tumor had a SOS1-ALK fusion which the breakpoints was (S2, A20) rather than other actionable mutations. Therefore, the patient received first-line crizotinib and experienced a remarkable tumor response and has tolerated crizotinib well until this writing. CONCLUSION: Considering this rare SOS1-ALK fusion and remarkable response to an ALK-inhibitor, it is important to be aware of the presence of SOS1-ALK fusions in patients with advanced NSCLC to better guide targeted therapy. Precision methods, such as NGS for oncogenic alteration detection, should also be encouraged in clinical practice.