Background Our previous studies have identified CA916798 as a chemotherapy resistance-associated gene in lung cancer. However, the histopathological relevance and biological function of CA916798 in lung adenocarcinoma (LUAD) remains to be delineated. In this study, we further investigated and explored the clinical and biological significance of CA916798 in LUAD. Methods The relationship between CA916798 and clinical features of LUAD was analyzed by tissue array and online database. CCK8 and flow cytometry were used to measure cell proliferation and cell cycle of LUAD after knockdown of CA916798 gene. qRT-PCR and western blotting were used to detect the changes of cell cycle-related genes after knockdown or overexpression of CA916798. The tumorigenesis of LUAD cells was evaluated with or without engineering manipulation of CA916798 gene expression. Response to Gefitinib was evaluated using LUAD cells with forced expression or knockdown of CA916798. Results The analysis on LUAD samples showed that high expression of CA916798 was tightly correlated with pathological progression and poor prognosis of LUAD patients. A critical methylation site in promoter region of CA916798 gene was identified to be related with CA916798 gene expression. Forced expression of CA916798 relieved the inhibitory effects of WEE1 on CDK1 and facilitated cell cycle progression from G2 phase to M phase. However, knockdown of CA916798 enhanced WEE1 function and resulted in G2/M phase arrest. Consistently, chemical suppression of CDK1 dramatically inhibited G2/M phase transition in LUAD cells with high expression of CA916798. Finally, we found that CA916798 was highly expressed in Gefitinib-resistant LUAD cells. Exogenous expression of CA916798 was sufficient to endow Gefitinib resistance with tumor cells, but interference of CA916798 expression largely rescued response of tumor cells to Gefitinib. Conclusions CA916798 played oncogenic roles and was correlated with the development of Gefitinib resistance in LUAD cells. Therefore, CA916798 could be considered as a promising prognostic marker and a therapeutic target for LUAD.
BackgroundSilicosis, a severe lung disease caused by inhaling silica dust, predominantly affects workers in industries such as mining and construction, leading to a significant global public health challenge. The purpose of this study is to analyze the current disease burden of silicosis and to predict the development trend of silicosis in the future the world by extracting data from the GBD database.MethodsWe extracted and analyzed silicosis prevalence, incidence, mortality, and disability-adjusted life years (DALYs) data from the Global Burden of Disease 2019 program for 204 countries and territories from 1990 to 2019. The association between the Sociodemographic Index (SDI) and the burden of age-standardized rates (ASRs) of DALYs has been examined at the regional level. Jointpoint regression analysis has been also performed to evaluate global burden trends of silicosis from 1990 to 2019. Furthermore, Nordpred age-period-cohort analysis has also been projected to predict future the burden of silicosis from 2019 to 2044.ResultsIn 2019, global ASRs for silicosis prevalence, incidence, mortality, and DALYs were 5.383, 1.650, 0.161, and 7.872%, respectively which are lower than that in 1990. The populations of 45–59 age group were more susceptible to silicosis, while those aged 80 or above suffered from higher mortality and DALY risks. In 2019, the most impacted nations by the burden of silicosis included China, the Democratic People’s Republic of Korea, and Chile. From 1990 to 2019, most regions observed a declining burden of silicosis. An “M” shaped association between SDI and ASRs of DALYs for silicosis was observed from 1990 to 2019. The age-period-cohort analysis forecasted a decreasing trend of the burden of silicosis from 2019 to 2044.ConclusionDespite the overall decline in the global silicosis burden from 1990 to 2019, some regions witnessed a notable burden of this disease, emphasizing the importance of targeted interventions. Our results may provide a reference for the subsequent development of appropriate management strategies.
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