Background: Small cell lung cancer (SCLC) represents about 13% of lung cancer cases, which is highly invasive and has a high mortality rate, with the 5-year overall survival (OS) rate being only 6.3%. Age at diagnosis of advanced SCLC is much older, but studies describing the ageing factor for distant metastasis patterns and prognosis of extensive-stage SCLC (ES-SCLC) are limited. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 18,682 patients with ES-SCLC (9,089 women and 9,053 men) who had complete clinical information between 2008 and 2015. Patients were classified into three groups (older group: ≥80 yrs, middle-aged group: 60-79 yrs, and younger group: ≤59 yrs). The role of different age at diagnosis of ES-SCLC (especially older group) in metastasis patterns was investigated, and OS and cancer-specific survival (CSS) of different age groups of metastatic ES-SCLC was assessed. Results: The most metastasis of ES-SCLC patients in the three groups was multiorgan metastases (MOM) metastasis (71.2%, 70.3% and 66.3%, respectively), the most single organ metastasis in the younger group was the lung (3.3%), the middle-aged group and the older group were the brain (3.5%, 3.1%, respectively). The analysis revealed that older patients were less likely to have MOM, but more likely to have all organs metastases than other two groups (p<0.001). Older group had the worst OS (p<0.001) and CSS (p<0.001). Furthermore, Radiotherapy and chemotherapy can improve survival (p<0.001), but the rate of radiotherapy and chemotherapy in older patients is lower than that in middle-aged and younger patients (50.4% vs 38.6% vs 20.7%, p<0.05). Compared with other two group, older group (odds ratios, ORs) for lung, all organ metastases, and MOM were 0.43 (95% CI 0.27-0.67), 1.77 (95% CI 1.55-2.03), 0.68 (95% CI 0.6-0.77), respectively. Conclusion: The mortality risk is highest with MOM and all organs metastasis followed by brain, lung, bone and liver metastases in elderly ES-SCLC patients. These results will be helpful for pre-treatment evaluation regarding the prognosis of ES-SCLC patients.

Introduction: Gefitinib is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) widely used in lung adenocarcinoma (LUAD) patients harboring sensitive EGFR mutations. Although it has a good initial efficacy, acquired resistance to gefitinib is eventually inevitable. Studies have shown that circular RNA (circRNA) is involved in the development of acquired resistance to different anti-cancer drugs, but the comprehensive analysis of its expression profile and functions on acquired gefitinib resistance remains poor. Methods: To explore the aberrant circRNAs expression profiles, we collected peripheral plasma samples from 4 gefitinib-sensitive and 4 gefitinib-resistant patients for performing microarray analysis. Candidates of differentially expressed circRNAs were used and analyzed by bioinformatics modalities including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a constructed circRNA-microRNA RNA network. The differential expression of selected circRNAs was verified by quantitative real-time PCR (qRT-PCR). Results: A total of 2571 circRNAs with significantly different expression between the groups were identified by microarray analysis. GO, KEGG, and pathway enrichment analyses reveal that these differentially expressed circRNAs (DECs) were complicated in many biological pathways that may be related to EGFR-TKI resistance such as ABC transporter and PI3K-Akt pathways. A circRNA-microRNA network was constructed by 10 circRNAs potentially involved in EGFR-TKI resistance togethering with their corresponding microRNAs (miRNAs). Consistent with the results of microarray assay, hsa_circ_0030591 and hsa_circ_0040348 were validated to be upregulated in gefitinib-resistant patients by qRT-PCR. Conclusions: Our study provides valuable data on circRNAs expression profiles detected in liquid biopsy for LUAD patients with acquired gefitinib resistance, and we validate that upregulations of hsa_circ_0030591 and hsa_circ_0040348 may play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker.

Background Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, which is a serious threat to human health. Adenylate cyclase associated protein 1 (CAP1) is an important functional protein, which is closely related to the occurrence and progression of cancer. Methods In this study, we used the CRISPR-dCas9-Dnmt3a system to target the CAP1 promoter to construct LUAD cell strains that can steadily up-regulate the methylation of CAP1 promoter. The methylation specific PCR and Massarray methylation sequencing were used to detect the methylation of CAP1 promoter. The western blot and immunohistochemistry were used to detect protein expression. The functional changes of LUAD cells were detected by CCK-8 assay, colony formation assay, flow cytometry assay, wound healing assay and trans-well assay. Results In this study, we found that the CAP1 promoter was abnormally hypo-methylated in LUAD cells and tissues. The expression of CAP1 protein was higher in cancerous tissues compared to para-carcinoma tissues in early stage LUAD, and higher in A549, H1299 and PC9 cells than in Beas-2B control cells (P < 0.05). Up-regulating methylation of CAP1 promoter can reduce the expression of CAP1 protein, promote apoptosis of LUAD cells through Bax/Bcl-2/Caspase-3 pathway, and inhibit the migration and invasion of LUAD cells by acting together with Actin and Cofilin. The methylation of CAP1 promoter is regulated by Dnmt3a, Tet1 and/or Tet2. Conclusions These results suggest that abnormal hypo-methylation of CAP1 gene enhances biological characteristics of LUAD cells and up-regulating methylation of CAP1 promoter may be a potential treatment for LUAD.

No abstract