ABSTRACT
BACKGROUND: Although visceral pleural invasion, lymphovascular invasion, tumor spread through air spaces, and poor differentiation are pathological risk factors associated with unfavorable prognosis in patients with lung adenocarcinoma, the cumulative impact of these factors on prognosis remains unclear. METHODS: We enrolled 1532 patients with stage I lung adenocarcinoma. Patients were divided according to the number of risk factors as follows: Group A (without risk factors), Group B (one risk factor), and Group C (multiple risk factors). Moreover, we stratified patients into two subgroups based on tumor size (≤ 3 cm, 3-4 cm). Kaplan-Meier analysis was used to evaluate 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Overall, 949, 404, and 179 patients were included in Groups A, B, and C, respectively. Group C had a larger tumor size and more cases of extrathoracic recurrence than the other groups. The 5-year DFS and OS gradually decreased across Groups A to C (DFS: 94.3%, 80.6%, and 64.3%, respectively, p < 0.001; OS: 97.2%, 92.7%, and 77%, respectively, p < 0.001). A similar trend was observed for tumors ≤ 3 cm in size (DFS: 95.2%, 83.2%, and 68.5%, respectively, p < 0.001; OS: 97.6%, 94.1%, and 79.6%, respectively, p < 0.001), but a less pronounced trend was observed for tumors between 3 and 4 cm in size (DFS: 72.1, 60.8, and 43.3%, respectively, p = 0.054; OS: 85.7, 82.1, and 64.7%, respectively, p = 0.16). CONCLUSIONS: Postoperative survival worsened with increasing pathological risk factors in patients with stage I lung adenocarcinoma, especially those with tumor size ≤ 3 cm.
ABSTRACT
BACKGROUND: Highest mediastinal lymph node (HMLN) involvement is a category of uncertain resection, yet the prognostic significance of HMLN involvement remains controversial. METHODS: A total of 486 patients with pathological stage III-N2 disease who underwent radical resection were enrolled from January 2015 to December 2018. Patients were allocated into two groups-HMLN involvement (219 cases) and HMLN-negative (249 cases) groups. Kaplan-Meier analysis and Cox proportional hazard regression models were used to evaluate the impact of HMLN involvement on 5-year recurrence-free survival (RFS) and overall survival (OS). RESULTS: The proportion of patients with multiple N2 diseases (72.1% vs. 23.7%; p < 0.001) and stage IIIA (87.2% vs. 77.5%; p < 0.009) were greater in the HMLN-involvement group than in the HMLN-negative group, and the survival rates of the HMLN-involvement group were significantly lower than those of the HMLN-negative group (RFS: 27.2% vs. 49.8%, p < 0.001; OS: 42.1% vs. 59.2%, p = 0.001). HMLN status was an independent factor for OS only (RFS: adjusted hazard ratio [aHR] 1.26, 95% confidence interval CI 0.94-1.68; OS: aHR 1.45, 95% CI 1.07-1.99) in the entire stage III cohort. After stratification of patients according to stage, the involvement of HMLN decreased both RFS and OS in the stage IIIA group (RFS: aHR 1.46, 95% CI 1.06-2.02; OS: aHR 1.70, 95% CI 1.19-2.42); however, no such difference was observed within the stage IIIB group. CONCLUSIONS: HMLN involvement is a prognostic factor of deteriorating survival in highly advanced N2 disease only in patients with stage IIIA.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lymph Nodes , Lymphatic Metastasis , Mediastinum , Neoplasm Staging , Humans , Male , Female , Survival Rate , Middle Aged , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/mortality , Mediastinum/pathology , Lymph Nodes/pathology , Lymph Nodes/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/mortality , Prognosis , Follow-Up Studies , Retrospective Studies , Aged , Pneumonectomy , Lymph Node ExcisionABSTRACT
Exosomes mediate cellular communications in cancer by transmitting active molecules. However, the CAFs-derived molecular determinants that regulate esophageal squamous cell carcinoma (ESCC) metastasis have not been fully characterized. The purpose of this study was to investigate the potential roles of exosomal LINC01410 of ESCC cells. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA). The expression of LINC01410 and miR-122-5p was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The biological roles of LINC01410 in ESCC cells were investigated using transwell assay. Western blot assay was employed to detect protein levels. The potential downstream molecular mechanism of LINC01410 was demonstrated with dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down. CAFs promote the metastasis and epithelial-mesenchymal transition (EMT) of ESCC cells. CAFs exert their roles by transferring exosomes to ESCC cells, leading to a significant increase of LINC01410 level in ESCC cells. Mechanically, LINC01410 secreted by CAFs-Exo could contribute to metastasis and EMT by sponging miR-122-5p and increasing PKM2 level in TE-1 and Eca-109 cells. Additionally, LINC01410/miR-122-5p/PKM2 axis affecting ESCC metastasis and EMT in vitro and in vivo.
Subject(s)
Cancer-Associated Fibroblasts/metabolism , Epithelial-Mesenchymal Transition/physiology , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/metabolism , Exosomes/metabolism , Animals , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Gene Expression Regulation, Neoplastic/physiology , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolismABSTRACT
BACKGROUND: SMARCD3 has recently been shown to be an important gene affecting cancer, playing an important role in medulloblastoma and pancreatic ductal adenocarcinoma. Therefore, we conducted this research to investigate the potential involvement of SMARCD3 across cancers and to offer recommendations for future studies. METHODS: Utilizing information on 33 malignancies in the UCSC Xena database, SMARCD3 expression and its prognostic value were assessed. The tumor microenvironment was evaluated with the "CIBERSORT" and "ESTIMATE" algorithms. SMARCD3 and immune-related genes were analyzed using the TISIDB website. The pathways related to the target genes were examined using GSEA. MSI (microsatellite instability), TMB (tumor mutational burden), and immunotherapy analysis were used to evaluate the impact of target genes on the response to immunotherapy. RESULTS: There is heterogeneity in terms of the expression and prognostic value of SMARCD3 among various cancers, but it is a risk factor for many cancers including uterine corpus endometrial cancer (UCEC), renal clear cell carcinoma (KIRC), and gastric adenocarcinoma (STAD). GSEA revealed that SMARCD3 is related to chromatin remodeling and transcriptional activation, lipid metabolism, and the activities of various immune cells. The TMB and MSI analyses suggested that SMARCD3 affects the immune response efficiency of KIRC, LUAD and STAD. Immunotherapy analysis suggested that SMARCD3 may be a potential immunotherapy target. RT-qPCR demonstrated the variation in SMARCD3 expression in KIRC, LUAD, and STAD. CONCLUSION: Our study revealed that SMARCD3 affects the prognosis and immunotherapy response of some tumors, providing a direction for further research on this gene.
Subject(s)
Biomarkers, Tumor , Immunotherapy , Neoplasms , Tumor Microenvironment , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/therapy , Microsatellite Instability , Gene Expression Regulation, Neoplastic , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolismABSTRACT
The determination of biomarkers in the blood specific for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) is crucial for the selection of effective treatment strategies and the prediction of prognosis. The purpose of the present study was to analyze the differentially expressed genes (DEGs) in LUSC and LUAD from The Cancer Genome Atlas (TCGA) database. In order to identify the potential biomarkers for non-small cell lung cancer (NSCLC) for clinical diagnosis, bioinformatics was used to analyze the DEGs of two subtypes of NSCLC, LUAD and LUSC. Exosomes were isolated from the serum of patients with LUAD or LUSC and identified using transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. A total of four differential exosomal mRNAs were selected for validation with serum samples from 70 patients with NSCLC via reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curves were established to evaluate the clinical diagnostic value of four DEGs for patients with LUAD and LUSC. The analysis based on TCGA data revealed the DEGs in LUSC and LUAD: A total of 1,619 genes were differentially expressed in patients with LUSC and LUAD. DEGs analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that inflammation-related signaling pathways, such as complement pathways, and multiple autoimmune diseases, such as systemic lupus erythematosus and asthma were mainly enriched in LUAD. The cell cycle, Hippo signaling pathway, Rap1 signaling pathway and Wnt signaling pathway were the main signaling pathways enriched in LUSC. The combination of tumor protein P63 (TP63), keratin 5 (KRT5), CEA cell adhesion molecule 6 (CEACAM6) and surfactant protein B (SFTPB) improved the specificity and sensitivity in the diagnosis of different lung cancer subtypes. Exosomal TP63, KRT5, CEACAM6 and SFTPB mRNAs can thus be used as biomarkers to differentiate between LUSC and LUAD, and may provide a novel strategy for their differential diagnosis and treatment.