ABSTRACT
The efficacy of radiotherapy, a cornerstone in the treatment of lung adenocarcinoma (LUAD), is profoundly undermined by radiotolerance. This resistance not only poses a significant clinical challenge but also compromises patient survival rates. Therefore, it is important to explore this mechanism for the treatment of LUAD. Multiple public databases were used for single-cell RNA sequencing (scRNA-seq) data. We filtered, normalized and downscaled scRNA-seq data based on the Seurat package to obtain different cell subpopulations. Subsequently, the ssGSEA algorithm was used to assess the enrichment scores of the different cell subpopulations, and thus screen the cell subpopulations that are most relevant to radiotherapy tolerance based on the Pearson method. Finally, pseudotime analysis was performed, and a preliminary exploration of gene mutations in different cell subpopulations was performed. We identified HIST1H1D+ A549 and PIF1+ A549 as the cell subpopulations related to radiotolerance. The expression levels of cell cycle-related genes and pathway enrichment scores of these two cell subpopulations increased gradually with the extension of radiation treatment time. Finally, we found that the proportion of TP53 mutations in patients who had received radiotherapy was significantly higher than that in patients who had not received radiotherapy. We identified two cellular subpopulations associated with radiotherapy tolerance, which may shed light on the molecular mechanisms of radiotherapy tolerance in LUAD and provide new clinical perspectives.
Subject(s)
Adenocarcinoma of Lung , Gene Expression Regulation, Neoplastic , Lung Neoplasms , Mutation , Radiation Tolerance , Single-Cell Analysis , Humans , Single-Cell Analysis/methods , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/radiotherapy , Adenocarcinoma of Lung/pathology , Radiation Tolerance/genetics , Lung Neoplasms/genetics , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Gene Expression Regulation, Neoplastic/radiation effects , Sequence Analysis, RNA/methods , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , A549 Cells , Gene Expression Profiling , Cell Line, TumorABSTRACT
Circular RNAs are vital players in tumorigenesis. We held the purpose to investigate the role and mechanism of circ_0103809 in non-small cell lung cancer (NSCLC). The expressions of circ_0103809, miR-153-3p and HDAC1 mRNA were determined using quantitative real-time PCR assay, and HDAC1 protein was quantified using western blot analysis. MTT, EdU, flow cytometry, tube-formation, wound healing and tube-formation assays were conducted for functional analysis. The predicted relationship among circ_0103809, miR-153-3p and HDAC1 was ascertained using dual-luciferase analysis, RIP assay and pull-down analysis. Animal models were further constructed to realize circ_0103809's role in vivo. Circ_0103809 was upregulated NSCLC specimens, cells and serum-derived exosomes. Serum exosomal circ_0103809 had the potency to be a diagnostic biomarker for NSCLC. Circ_0103809 silencing inhibited NSCLC cell growth, metastasis and angiogenesis and triggered cell cycle arrest and apoptosis. Circ_0103809 deficiency also suppressed the growth of transplanted tumors. Circ_0103809 acted as the miR-153-3p sponge, and the biological effects of circ_0103809 knockdown were relieved by miR-153-3p inhibition. HDAC1 was directly targeted by miR-153-3p, and miR-153-3p enrichment inhibited NSCLC cell malignant phenotypes by sequestering HDAC1. Circ_0103809 knockdown repressed NSCLC malignant progression partly by regulating miR-153-3p/HDAC1 signaling.
ABSTRACT
@#Objective To investigate the preoperative localization of pulmonary glabrous nodules. Methods A total of 192 patients admitted to General Hospital of Northern Theater Command from April 2012 to September 2019 were selected for the study. There were 95 males and 97 females at an age of 56.47±11.79 years. All patients completed preoperative examination, and were divided into a positioning group (n=97) and a non-positioning group (n=95) according to whether the preoperative positioning was performed. And the surgical indicators between the two groups were compared. According to the substance of ground-glass opacity, they were divided into a pure ground-glass nodules group (n=23) and a mixed ground-glass nodules group (n=74) in the positioning group and a pure ground-glass nodules group (n=14) and a mixed ground-glass nodules group (n=81) in the non-positioning group . According to the size and distance of the nodules from the pleura and whether the nodules could be detected, the corresponding linear function was obtained. Results The operative time of methylene blue localization group was shorter than that of the no localization group. In the scatter plot, the corresponding diameter and depth of the nodules and the corresponding coordinate points which can be explored were described. And linear regression was performed on all the coordinate points to obtain the linear function: depth=0.648×diameter–1.446 (mm). It can be used as an indication for the preoperative localization of pure ground-glass nodules in Da Vinci robotic surgery. Linear function: depth=0.559 5×diameter+0.56 (mm). It can be used as an indication of preoperative localization of mixed ground-glass nodules in Da Vinci robotic surgery. Conclusion This equation can be used as a preoperative indication for clinical peripheral pulmonary ground-glass nodules.
