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 explore the role of cyclin B1 (CCNB1), cyclin B2 (CCNB2) and cyclin dependent kinase 1 (CDK1) in lung adenocarcinoma (LUAD) using bioinformatic data. Methods First, RNA expression data were downloaded from two datasets in Gene Expression Omnibus (GEO), and DESeq2 software was used to identify deferentially expressed genes (DEGs). Subsequent analyses were conducted based on the results of these DEGs: protein-protein interaction (PPI) network was constructed with STRING database; the modules in PPI network were analyzed by Molecular Complex Detection software, and the most significant modules were selected, the genes included in these modules were the hub genes; high-throughput RNA sequencing data from other databases were used to verify the expression of these hub genes to confirm whether they were DEGs; survival curve analyses of the confirmed DEGs were conducted to select genes that had significant influence on the survival of LUAD; the expression of these hub genes in different stages of LUAD were also analyzed. Then, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for these selected hub genes using KOBAS database. MuTarget tool was used to analyze the correlations between the expression of these selected hub genes and gene mutation status in LUAD. The potential value of these hub genes in the treatment of LUAD was explored based on the drug information in GDSC database. Finally, immunohistochemical data from Human Protein Atlas (HPA) database were used to verify the expression of these hub genes in LUAD again. Results According to the expression data in GEO, 594 up-regulated genes and 651 down-regulated genes were identified (P<0.05), among which 30 hub genes were selected for subsequent analyses. The RNA high-throughput sequencing data of other databases verified that 18 genes were DEGs, among which 8 hub genes had significant impact on disease-free survival in LUAD (P<0.05). Moreover, the 8 genes were differentially expressed in different stages of LUAD, which were higher in the middle and late stage of LUAD. Among the 8 genes. CCNB1, CCNB2 and CDK1 were significantly enriched in the cell cycle pathway. The expression of CCNB1, CCNB2 and CDK1 in LUAD was closely related to the TP53 mutation status. In addition, CDK1 was associated with four drugs, revealing the potential value of CDK1 in the treatment of LUAD. Finally, immunohistochemical data from HPA database verified that CCNB1, CCNB2 and CDK1 were highly expressed in LUAD in the protein level. Conclusion Overexpression of CCNB1, CCNB2 and CDK1 are associated with poor prognosis of LUAD, indicating that the three genes may be prognostic biomarkers of LUAD and CDK1 is a potential therapeutic target for LUAD.
ObjectiveTo investigate the effect of different lymph node dissection methods on the prognosis of patients with stage ⅠA spread through air space (STAS)-positive lung adenocarcinoma≤ 2 cm. MethodsClinical data of 3148 patients with lung adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, the First Affiliated Hospital of University of Science and Technology of China from 2016 to 2018 were retrospectively analyzed. Patients with stage ⅠA STAS-positive lung adenocarcinoma≤ 2 cm were included and divided into two groups based on lymph node dissection methods: systematic lymph node dissection group and limited lymph node dissection group. Compare the clinical and pathological data of two groups of patients and use Cox proportional hazards regression model for multivariate survival analysis. ResultsA total of 209 STAS-positive patients were enrolled in the study, including 98 males and 111 females, aged 28-83 (60.42±10.15) years. Univariate analysis showed that the mode of lymph node dissection, past history, micropapillary histological subtype, and papillary histological subtype were risk factors for patient prognosis. Multifactorial analysis showed that lymph node dissection method, age, and micropapillary histological subtype were risk factors for patient prognosis. Meanwhile, among STAS-positive patients, systematic lymph node dissection had a better prognosis than limited lymph node dissection patients. ConclusionSTAS plays an important role in patient prognosis as an independent risk factor for prognosis of stage ⅠA ≤2 cm lung adenocarcinoma. When STAS is positive, the choice of systematic lymph node dissection may be more favourable to patients' long-term prognosis.
ObjectiveTo explore the effectiveness of Ovol2 gene for epithelial-mesenchymal transition (EMT) to offer some theory evidences for the targeted therapy in lung adenocarcinoma. MethodsA549 cells were treated with control and Ovol2 overexpressioned by lentivirus infection. Real-time PCR were performed to test the mRNA level of genes correlated to EMT. Western Blot was performed for protein level of the following makers:E-cadherin, N-cadherin, vimentin, ect. Moreover, we tested the migration and invasion ability of A549 cells by transwell and wound healing experiment. ResultsAfter treated with Ovol2 overexpressed, the expression level of E-cadherin raised, while the expression level of N-cadherin, vimentin and Twist1 declined in both mRNA and protein expression level. The results of wound healing and transwell experiment indicated that the migration and invasion ability of A549 cells weakened. ConclusionOverexpression of Ovol2 gene can suppress the distant metastasis ability and invasion ability of A549 cells by inhibiting the EMT.
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 explore the molecular mechanism of LINC00626 regulating malignant progression of lung adenocarcinoma metastasis through JAK1/STAT3/KHSRP axis. Methods Quantitative real-time polymerase chain polymerase chain reaction was used to detect the expression of LINC00626 and KHSRP mRNA in human non-small-cell lung carcinoma cell lines (A549, H1299, H1975, H1437), human normal bronchial epithelial cell line (16HBE) and 144 lung adenocarcinoma tissues. The knockdown LINC00626 lentivirus and the control lentivirus were transferred into H1299 and H1437 cells, and named as sh-LINC00626 group (silencing of LINC00626 by transfecting short hairpin RNA lentiviral vector and sh-NC Group negative control by transfecting short hairpin RNA lentiviral). The overexpressed LINC00626 lentivirus and the control lentivirus were transferred into A549 and H1975 cells and named as LINC00626 group and Vector group. KHSRP vector on the basis of silencing LINC00626 and blank vector on the basis of silencing LINC00626 were added in H1437 cells. Cell counting kit-8 assay and Transwell migration/invasion assay were used to detect cell proliferation, migration and invasion. The expression levels of JAK/STAT and KHSRP in stably transfected cells were detected by Western blot. The effect of LINC00626 in vivo was studied in nude mice. Nuclear-cytoplasmic separation and RNA fluorescence in situ hybridization assay are used to predict the subcellular localization of LINC00626 and KHSRP. RNA pull down and mass spectrometry analysis were used to identify LINC00626 binding proteins. Results The expression levels of LINC00626 and KHSRP in non-small-cell lung carcinoma cell lines were significantly higher than those in normal human bronchial epithelial cells. LINC00626 and KHSRP were highly expressed in lung adenocarcinoma. Compared with the control group, the cell proliferation rate, colony formation, cell migration and invasion of H1437 cells were significantly decreased in knockdown group, while the reverse was true for over-expression. LINC00626 and KHSRP were located in the nucleus. LINC00626 directly binded to the KHSRP protein. Compared with the control group, H1437 cells transfected with knockdown LINC00626 and KHSRP significantly increased cell proliferation rate, cell migration, number of invasions. Compared with the control group, knockdown group showed a significant decrease in tumor volume and weight, cell proliferation rate and proliferation index, and the number of lung metastases. While the overexpression group showed an opposite effect, there were significant differences among the groups (P<0.01). The expression of JAK1 and STAT3 mRNA and protein in sh-LINC00626 group was lower than that in sh-NC Group (P<0.05), and the expression of JAK1 and STAT3 mRNA and protein in sh-LINC00626 group was higher than that in Vector group (P<0.05). Conclusion LINC00626 promotes malignant progression of lung adenocarcinoma metastasis through JAK1/STAT3/KHSRP signaling axis.
Lung cancer is one of the malignant tumors with the greatest threat to human health, and studies have shown that some genes play an important regulatory role in the occurrence and development of lung cancer. In this paper, a LightGBM ensemble learning method is proposed to construct a prognostic model based on immune relate gene (IRG) profile data and clinical data to predict the prognostic survival rate of lung adenocarcinoma patients. First, this method used the Limma package for differential gene expression, used CoxPH regression analysis to screen the IRG to prognosis, and then used XGBoost algorithm to score the importance of the IRG features. Finally, the LASSO regression analysis was used to select IRG that could be used to construct a prognostic model, and a total of 17 IRG features were obtained that could be used to construct model. LightGBM was trained according to the IRG screened. The K-means algorithm was used to divide the patients into three groups, and the area under curve (AUC) of receiver operating characteristic (ROC) of the model output showed that the accuracy of the model in predicting the survival rates of the three groups of patients was 96%, 98% and 96%, respectively. The experimental results show that the model proposed in this paper can divide patients with lung adenocarcinoma into three groups [5-year survival rate higher than 65% (group 1), lower than 65% but higher than 30% (group 2) and lower than 30% (group 3)] and can accurately predict the 5-year survival rate of lung adenocarcinoma patients.
ObjectiveTo investigate the risk factors for lymph node metastasis in resectable lung adenocarcinoma by combining spatial location, clinical, and imaging features, and to construct a lymph node metastasis prediction model. MethodsA retrospective study on patients who underwent chest computed tomography (CT) at the First Affiliated Hospital of Nanjing Medical University from June 2016 to June 2020 and were surgically confirmed to have invasive lung adenocarcinoma with or without lymph node metastasis was conducted. Patients were divided into a positive group and a negative group based on the presence or absence of lymph node metastasis. Clinical and imaging data of the patients were collected, and the independent risk factors for lymph node metastasis in resectable lung adenocarcinoma were analyzed using univariate and multivariate logistic regression. A combined spatial location-clinical-imaging feature prediction model for lymph node metastasis was established and compared with the traditional lymph node metastasis prediction model that does not include spatial location features. ResultsA total of 611 patients were included, with 333 in the positive group, including 172 males and 161 females, with an average age of (58.9±9.7) years; and 278 in the negative group, including 127 males and 151 females, with an average age of (60.1±11.4) years. Univariate and multivariate logistic regression analyses showed that the spatial relationship of the lesion to the lung hilum, nodule type, pleural changes, and serum carcinoembryonic antigen (CEA) levels were independent risk factors for lymph node metastasis. Based on this, the combined spatial location-clinical-imaging feature prediction model had a sensitivity of 91.67%, specificity of 74.05%, accuracy of 87.88%, and area under the curve (AUC) of 0.885. The traditional lymph node metastasis prediction model, which did not include spatial location features, had a sensitivity of 76.40%, specificity of 72.10%, accuracy of 53.86%, and AUC of 0.827. The difference in AUC between the two prediction methods was statistically significant (P=0.026). Compared with the traditional prediction model, the predictive performance of the combined spatial location-clinical-imaging feature prediction model was significantly improved. ConclusionIn patients with resectable lung adenocarcinoma, those with basal spatial location, solid density, pleural changes with wide base depression, and elevated serum CEA levels have a higher risk of lymph node metastasis.
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.
Lung ground glass opacity (GGO), which is associated with the pathology of the lung adenocarcinoma, is drawing more and more attention with the increased detection rate. However, it is still in the research stage for the imaging interpretation of GGO lesions. In this paper, we reviewed and analyzed the new classification of lung adenocarcinoma corresponding to the interpretation of GGO imaging feature, which emphasizes on how to determine the GGO lesions comprehensively and quantitative determination of the invasive extent of GGO.