ObjectiveTo investigate the CT signs and clinicopathological features of peripheral cavitary lung adenocarcinoma with the largest diameter less than or equal to 3 cm.Methods From January 2015 to December 2017, the CT signs and clinicopathological fertures of 51 patients with ≤3 cm peripheral cavitary lung adenocarcinoma diagnosed by chest CT and surgical pathology were retrospectively analyzed. Furthermore, CT signs and clinicopathological features of thick-walled cavitary lung adenocarcinoma and thin-walled cavitary lung adenocarcinoma were compared. There were 29 males and 22 females at age of 62 (56, 67) years.ResultsThere were 27 thick-walled cavitary lung adenocarcinoma and 24 thin-walled cavitary lung adenocarcinoma. Thick-walled cavitary adenocarcinoma had greater SUVmax [6.5 (3.7, 9.7) vs. 2.2 (1.4, 3.8), P=0.019], larger cavity wall thickness (11.8±4.6 mm vs. 7.6±3.7 mm, P=0.001), larger tumor tissue size [2.1 (1.7, 2.8) cm vs. 1.6 (1.2, 2.0) cm, P=0.006], and more solid nodules (17 patients vs. 8 patients, P=0.035). Thin-walled cavitary adenocarcinoma had more smoking history (12 patients vs. 6 patients, P=0.038), larger cavity size [12.3 (9.2, 16.6) mm vs. 4.4 (2.8, 7.1) mm, P=0.000], and larger proportion of cavities [0.30 (0.19, 0.37) vs. 0.03 (0.01, 0.09), P=0.000]. On CT signs, there were more features of irregular inner wall (19 patients vs. 6 patients, P=0.000), intra-cystic separation (16 patients vs. 6 patients, P=0.001) and vessels through the cystic cavity (10 patients vs. 1 patient, P=0.001) in thin-walled caviraty lung adenocarcinoma.ConclusionPeripheral cavitary lung adenocarcinoma of ≤3 cm on chest CT has characteristic manifestations in clinical, imaging and pathology, and there is a statistical difference between thick-walled cavitary lung adenocarcinoma and thin-walled cavitary lung adenocarcinoma.
Objective To investigate the molecular mechanisms by which the long non-coding RNA (lncRNA) MIR223HG affects the proliferation, migration and apoptosis of lung adenocarcinoma cells. MethodsDNA damaging agent Zeocin was used to treat human embryo lung cell (MRC-5) and lung cancer cell (A549 and H1299), and the expression of MIR223HG was tested by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, the ataxia-telangiectasia mutated (ATM) protein and ATM pathway downstream factor Cell cycle checkpoint kinase 2 (Chk2), p53 tumor suppressor protein (p53) in the lung cancer cell (A549 and H1299) with Zeocin were also tested by qRT-PCR. Cell transfection and Transwell migration assay, colony formation assays, apoptosis assays were performed to verify the role of ATM in the expression of MIR223HG in lung adenocarcinoma. ResultsThe expression of MIR223HG was reduced markedly in the lung cancer cells (A549 and H1299) compared with human embryo lung cell (MRC-5) after treated with Zeocin. ATM protein and its downstream factors Chk2, p53 involved in the process, and ATM regulated the expression of MIR223HG in the lung cancer cells with Zeocin. Futhermore, ATM joined in the processes that MIR223HG regulated the lung cancer cells proliferation, migration and apoptosis. Conclusions The expression of MIR223HG is related to the DNA damage response in the lung cancer, and MIR223HG regulates lung cancer cells proliferation, migration and apoptosis by ATM/Chk2/p53 pathway. MIR223HG may be a potential therapeutic target for lung adenocarcinoma treatment.
Objective To analyze the expression of H2A histone family, member X (H2AFX) gene in lung adenocarcinoma and its influence on prognosis. Methods We analyzed the expression level of H2AFX gene in the tumor tissues (497 cases) and normal adjacent tissues (54 cases) of lung adenocarcinoma patients via The Cancer Genome Atlas. The patients were divided into high expression group and low expression group according to the expression level of H2AFX gene in lung adenocarcinoma samples. The relationship between H2AFX and clinicopathological features of patients was analyzed through logistic regression. Kaplan-Meier survival curve and log-rank test were used to study the correlation between H2AFX expression and the prognosis of lung adenocarcinoma patients. Univariate and multiple Cox regression analyses were performed to determine the prognostic significance of H2AFX expression in lung adenocarcinoma patients. The research also covered H2AFX-related pathways of genes in the development of lung adenocarcinoma with gene set enrichment analysis (GSEA). Results The H2AFX expression was higher in lung adenocarcinoma tissues than that in normal adjacent tissues (P<0.001). Besides, it was significantly correlated with age (P<0.001), T staging (P=0.007), and N staging (P=0.010), but had little to do with M staging or gender (P>0.05). Kaplan-Meier survival curve and log-rank test showed that the survival rate of patients with high H2AFX expression was vastly lower than that of patients with low H2AFX expression (P<0.001). Multiple Cox regression analysis demonstrated that H2AFX could be an independent prognostic factor for lung adenocarcinoma [hazard ratio=1.41, 95% confidence interval (1.11, 1.78), P=0.004]. The results of GSEA displayed that H2AFX was involved in cell cycle, homologous recombination, DNA replication, base excision and repair, spliceosome, mismatch repair, p53 signaling pathway, nucleotide excision and repair, RNA degradation, RNA polymerase, and other pathways. Conclusions The expression of H2AFX gene is high in lung adenocarcinoma, and closely connected to the prognosis, occurrence, and evolution of lung adenocarcinoma. This gene can be one of the new molecular markers and therapeutic targets for lung adenocarcinoma.
Objective To investigate the effect of microRNA-27a (miR-27a) on the apoptosis of human lung adenocarcinoma cells A549 induced by lipopolysaccharide (LPS) by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway, and its mechanism is discussed preliminarily. Methods The complementary binding sites of miR-27a and phosphatidylinositol-3 kinase catalytic subunit delta (PIK3CD) were analyzed by Starbase and verified by double luciferase. The A549 cells were divided into normal group, LPS group, LPS+miR-27a mimic negative control group, LPS+miR-27a mimic group, LPS+miR-27a mimic+PI3K activator group. In the LPS+miR-27a mimic negative control group, LPS+miR-27a mimic group and LPS+miR-27a mimic+PI3K activator group, the cells were transfected with miR-27a mimic negative control, miR-27a mimic and miR-27a mimic, respectively, and were cultured for 6 h. After that, the cells were cultured in complete medium for 24 h, and then, except for the normal group, the cells in the other groups were stimulated with 10 mg/L LPS for 24 h, and the PI3K activator 740 Y-P was added to the LPS+miR-27a mimic+PI3K activator group, and cells in normal group were cultured in complete medium for the same time. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-27a in cells; cell counting kit 8 was used to detect cell proliferation; Hoechst33342 staining and flow cytometry was used to detect apoptosis; autophagy of A549 cells was observed by transmission electron microscope; Western blot was used to detect the expression of PIK3CD, phosphorylated-AKT (p-AKT), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and microtubule-associated protein 1 light chain 3 II (LC3II) protein. Results There was a binding site between miR-27a and PIK3CD, which was verified by double luciferase. Compared with those in normal group, the expression level of miR-27a, proliferation rate and protein expression level of Bcl-2 in LPS group and LPS+miR-27a mimic negative control group were lower (P<0.05), the apoptosis rate, protein expression levels of PIK3CD, p-AKT, Bax, cleaved caspase-3, LC3Ⅱ were higher (P<0.05); compared with those in LPS group and LPS+miR-27a mimic negative control group, the expression level of miR-27a, proliferation rate and protein expression level of Bcl-2 in LPS+miR-27a mimic group were higher (P<0.05), the apoptosis rate, protein expression levels of PIK3CD, p-AKT, Bax, cleaved caspase-3, LC3Ⅱ were lower (P<0.05); compared with those in LPS+miR-27a mimic group, the expression level of miR-27a and proliferation rate in LPS+miR-27a mimic+PI3K activator group were lower (P<0.05), the apoptosis rate, protein expression levels of PIK3CD, p-AKT, cleaved caspase-3, LC3Ⅱ were higher (P<0.05). The number of cells in the normal group was more, the cells were closely arranged, the nucleus size was uniform, and the organelle structure was normal; in LPS group and LPS+miR-27a mimic negative control group, cells became round, nuclei pyknosis, formed clumps, and showed multiple round autophagic vesicles of different sizes; the number of nuclear pyknotic cells in LPS+miR-27a mimic group decreased, and the number of nuclear pyknotic cells in LPS+miR-27a mimic+PI3K activator group increased compared with LPS+miR-27a mimic group, a small number of circular autophagic vesicles were observed, but the number was different. Conclusion Overexpression of miR-27a can inhibit PI3K/Akt pathway and reduce LPS induced apoptosis of human lung adenocarcinoma cells A549, which may be related to the reduction of autophagy.
Objective To investigate the biological characteristics and clinical significance of cuproptosis-related genes in lung adenocarcinoma (LUAD) based on the multi-omics data from The Cancer Genome Atlas. Methods The cuproptosis-related genes were obtained from a study published in Science in March 2022. The whole genome data were used to reveal the mutation spectrum and copy number variation landscape of cuproptosis-related genes in LUAD and analyze its effects on transcriptome expression. Cuproptosis-related genes were annotated using Metascape analysis to further understand the pathways or functions in which these genes were involved. Subsequent univariate Cox analysis and Kaplan-Meier methods determined the prognosis of these genes in LUAD patients, and CellMiner analysis were used to identify those potential anticancer drugs for potentially targeting cuproptosis-related genes. Results Cuproptosis-related genes were less frequently mutated in LUAD, and the effect of gene mutations on transcriptomic expression may depend on the type of mutation. Gene copy number variation was an important factor resulting in the disordered expression of cuproptosis-related genes. The 16 cuproptosis-related genes were mainly involved in glyoxylate metabolism and glycine degradation, copper ion entry, proteolitidylation, cellular amino acid catabolism process, oxidative stress response, etc. Among them, 6 genes (DLD, FDX1, DLAT, DLST, PDHA1, CDKN2A) were prognostic risk genes in LUAD. The CellMiner analysis suggested that 13 drugs were associated with 7 cuproptosis-related genes and they might be potential anticancer drugs for potentially targeting cuproptosis. Conclusion This study reveals the biological characteristics and clinical significance of cuproptosis-related genes in LUAD, and provides some reference and theoretical basis for the subsequent research of cuproptosis in cancer.
ObjectiveTo compare the the effectiveness of robot-assisted thoracic surgery (RATS) with video-assisted thoracic surgery (VATS), in stageⅠ lung adenocarcinoma.MethodsFrom January 2012 to December 2018, 291 patients were included. The patients were allocated into two groups including a RATS group with 125 patients and a VATS group with 166 patients. Two cohorts (RATS, VATS ) of clinical stageⅠ lung adenocarcinoma patients were matched by propensity score. Then there were 114 patients in each group (228 patients in total). There were 45 males and 69 females at age of 62±9 years in the RATS group; 44 males, 70 females at age of 62±8 years in the VATS group. Overall survival (OS) and disease-free survival (DFS) were assessed. Univariate and multivariate analyses were performed to identify factors associated with the outcomes.Results Compared with the VATS group, the RATS group got less blood loss (P<0.05) and postoperative drainage (P<0.05) with a statistical difference. There was no statistical difference in drainage time (P>0.05) or postoperative hospital stay (P>0.05) between the two groups. The RATS group harvested more stations and number of the lymph nodes with a statistical difference (P<0.05). There was no statistical difference in 1-year, 3-year and 5-year OS and mean survival time (P>0.05). While there was a statistical difference in DFS between the two groups (1-year DFS: 94.1% vs. 95.6%; 3-year DFS: 92.6% vs. 75.2%; 5-year DFS: 92.6% vs. 68.4%, P<0.05; mean DFS time: 78 months vs. 63 months, P<0.05) between the two groups. The univariate analysis found that the number of the lymph nodes dissection was the prognostic factor for OS, and tumor diameter, surgical approach, stations and number of the lymph nodes dissection were the prognostic factors for DFS. However, multivariate analysis found that there was no independent risk factor for OS, but the tumor diameter and surgical approach were independently associated with DFS.ConclusionThere is no statistical difference in OS between the two groups, but the RATS group gets better DFS.
ObjectiveTo investigate the relationship between the expression of programmed cell death ligand-1 (PD-L1) and the maximal standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the correlation of clinical factors between SUVmax values and PD-L1.MethodsThe clinical data of 84 patients with invasive lung adenocarcinoma diagnosed pathologically in West China Hospital, Sichuan University from August 2016 to November 2018 were analyzed retrospectively, including 38 males and 46 females, aged 60 (32-85) years. The tumor was acinar-predominant in 37 patients, papillary in 20, lepidic in 19, solid in 5 and micropapillary in 3. Multivariate analysis of the relationship between SUVmax value and other clinicopathological features was performed by linear regression. Logistic regression analysis was used to analyze the relationship between PD-L1 protein expression and other pathological features.ResultsThe SUVmax of the PD-L1 expression group was significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group (P=0.002) and intermediate-grade histologic subtype (P=0.016). The SUVmax cut-off value of PD-L1 expression in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype was 5.34 (AUC: 0.732, P=0.002) and 5.34 (AUC: 0.720, P=0.017), respectively. Multivariate analysis showed that pleura involvement, vascular tumor thrombus and the increase of tumor diameter could cause the increase of the SUVmax value, while the SUVmax value decreased in the moderately differentiated tumor compared with the poorly differentiated tumor. The SUVmax cut-off value between low-grade histologic subtype and intermediate-grade histologic subtype, intermediate-grade histologic subtype and high-grade histologic subtypes was 1.54 (AUC: 0.854, P<0.001) and 5.79 (AUC: 0.889, P<0.001), respectively. Multivariate analysis of PD-L1 expression showed pleura involvement (P=0.021, OR=0.022, 95%CI 0.001 to 0.558) and moderate differentiation (opposite to poor differentiation) (P=0.004, OR=0.053, 95%CI 0.007 to 0.042) decreased the expression of PD-L1.ConclusionThe SUVmax of the PD-L1 expression group is significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype. The level of SUVmax and the expression of PD-L1 in invasive lung adenocarcinoma are related to many clinical factors.
ObjectiveTo investigate the value of serum soluble CD146 (sCD146) in determining acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in lung adenocarcinoma.MethodsA total of 144 lung adenocarcinoma EGFR sensitive patients in People’s Hospital of Zhengzhou University diagnosed from January 2016 to December 2016 were recruited in the study. According to the different time of taking drugs, the patients were divided into a non-medication group (31 cases), a 1 to 3 month treatment group (25 cases), a 4 to 6 month treatment group (19 cases), a 7 to 12 month treatment group (25 cases), a drug-resistant group (24 cases), and a nonresistant group up to 1 year of treatment (20 cases). The serum levels of sCD146, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were measured by ELISA and chemiluminescence and compared between different period of medication. The relationship of serum sCD146 with tumor markers (CEA, NSE) and tumor related clinical parameters (age, gender, tumor stage, metastasis, tumor diameter, number of the lesions) were analyzed.ResultsThe serum sCD146 level was minimum in the non-medication group that did not receive pioglitazone treatment, highest in the 1 to 3 month treatment group (early treatment period), and declined with duration of medication until resistance occurred without significant difference (P>0.05). The level of sCD146 of the drug-resistant group was significantly lower than that of all nonresistant groups, with significant difference (allP<0.05), but still higher than that of the non-medication group (P<0.05). The serum sCD146 levels in the nonresistant patients with medication over 1 year and within 1 year were similar (P>0.05), and significantly higher than the non-medication group and drug-resistance group (allP<0.05). The serum CEA levels did not differ significantly between 6 groups (P>0.05). The serum NSE level of the 4 to 6 month treatment group was lower than that of the 7 to 12 month treatment group (P<0.05), but both in the normal reference range. The NSE levels did not differ in any other groups (P>0.05). Serum sCD146 was associated with metastasis (P<0.05), but not associated with serum CEA or NSE, nor with sex, age, tumor staging, tumor diameter or lesion number (allP>0.05).ConclusionsCD146 may be involved in the mechanism of TKI killing tumor cells and the mechanism of TKI resistance, and may be a serological marker for monitoring the efficacy of TKI and judging the resistance of TKI.
ObjectiveTo investigate the correlation between UBE2Q1 expression and clinicopathologic features and prognosis of lung adenocarcinoma. MethodsThis study retrospectively chose the cancer tissue and para-carcinoma tissue samples of 74 patients with stage I to III lung adenocarcinoma who received radical resection in Nanjing Chest Hospital from January 2013 to December 2016. Immunohistochemistry staining was used to detect the expression level of UBE2Q1, and patients were divided into high-expression group and low-expression group according to the Immunohistochemistry staining score. The correlation of UBE2Q1 expression level and clinicopathological characteristics was analyzed by Chi-square test. Kaplan-Meier survival curve analyzed the correlation between UBE2Q1 and prognosis of lung adenocarcinoma patients. The risk factors affecting the survival of lung adenocarcinoma patients were analyzed by univariate and multivariate Cox proportional risk models. ResultsUBE2Q1 was highly expressed in lung adenocarcinoma tissues, and the expression level was correlated with tumor diameter, lymph node metastasis, and TNM stage (P<0.05), and did not correlate with patients’ gender, age, smoking history, and tumor differentiation (P>0.05). The results of the Kaplan-Meier survival analysis showed that patients with low expression of UBE2Q1 compared with those with high expression of UBE2Q1 had longer DFS and OS (both P<0.05). Cox proportional risk model showed that tumor diameter, lymph node metastasis, TNM stage, and high UBE2Q1 expression were the risk factors for DFS and OS, among which TNM stage was an independent risk factor. ConclusionUBE2Q1 was highly expressed in lung adenocarcinoma tissues and correlated with large tumor diameter, lymph node metastasis, late TNM stage and poorer prognosis in lung adenocarcinoma, and UBE2Q1 was a risk factor for lung adenocarcinoma.