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1.
Chinese Journal of Lung Cancer ; (12): 889-900, 2024.
Article in Chinese | WPRIM | ID: wpr-1010096

ABSTRACT

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.


Subject(s)
Humans , Lung Neoplasms/genetics , Adenocarcinoma of Lung/genetics , China , Prognosis , Transcription Factors
2.
Chinese Journal of Lung Cancer ; (12): 881-888, 2024.
Article in Chinese | WPRIM | ID: wpr-1010097

ABSTRACT

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Dual Specificity Phosphatase 1/pharmacology , Cell Proliferation , p38 Mitogen-Activated Protein Kinases/pharmacology , Methylation , Apoptosis , Cell Line, Tumor
3.
Chinese Journal of Lung Cancer ; (12): 901-909, 2024.
Article in Chinese | WPRIM | ID: wpr-1010098

ABSTRACT

BACKGROUND@#The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.@*METHODS@#We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.@*RESULTS@#All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.@*CONCLUSIONS@#Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.


Subject(s)
Humans , Lung Neoplasms/metabolism , Interleukin-5/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use , Retrospective Studies , Programmed Cell Death 1 Receptor , Biomarkers , Immunotherapy , Disease Progression , B7-H1 Antigen
4.
Chinese Journal of Lung Cancer ; (12): 910-918, 2024.
Article in Chinese | WPRIM | ID: wpr-1010099

ABSTRACT

BACKGROUND@#The thoracic small biopsy sampling procedure including transbronchial forceps lung biopsy (TBLB) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) can be accompanied by rapid on-site evaluation (ROSE) of sample material to provide immediate feedback for the proceduralist. The present study aims to investigate the supplemental effect of ROSE smear samples for lung cancer molecular test.@*METHODS@#In a retrospective study, 308 patients admitted to our hospital from August 2020 to December 2022 undergoing diagnostic TBLB and EBUS-TBNA with ROSE and subsequently diagnosed as non-small cell lung cancer (NSCLC) were analyzed. The matched formalin-fixed paraffin-embedding (FFPE) tissue section and ROSE smears for tumor cellularity were compared. DNA yields of smears were determined. Real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS) were performed on adequate smear samples.@*RESULTS@#ROSE smear samples were enriched in tumor cells. Among 308 biopsy samples, 78 cases (25.3%) exhibited inadequate FFPE tissue sections, whereas 44 cases (14.3%) yielded adequate smear samples. Somatic mutations detected in the FFPE tissue section samples were also detected in the matching adequate smear sample.@*CONCLUSIONS@#ROSE smear samples of the thoracic small biopsies are beneficial supplemental materials for ancillary testing of lung cancer. Combined use of cytology smear samples with traditional FFPE section samples can enhance the detection rate of informative mutations in patients with advanced NSCLC. We recommend that the laboratory could further evaluate the ROSE cell smears of the patient when FFPE tissue sections are inadequate, and that adequate cell smears can be used as a supplemental source for the molecular testing of NSCLC.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Rapid On-site Evaluation , Retrospective Studies , Molecular Diagnostic Techniques , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods
5.
Chinese Journal of Lung Cancer ; (12): 919-933, 2024.
Article in Chinese | WPRIM | ID: wpr-1010100

ABSTRACT

BACKGROUND@#Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment. Long non-coding RNA (lncRNA) THAP7-AS1 is known to be highly expressed in gastric cancer, but has been less studied in other cancers. The aim of the study is to explore the role and mechanism of methyltransferase-like 3 (METTL3) mediated up-regulation of N6-methyladenosine (m6A) modified lncRNA THAP7-AS1 expression in promoting the development of lung cancer.@*METHODS@#Samples of 120 lung cancer and corresponding paracancerous tissues were collected. LncRNA microarrays were used to analyze differentially expressed lncRNAs. THAP7-AS1 levels were detected in lung cancer, adjacent normal tissues and lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of THAP7-AS1 in lung cancer and the relationship between THAP7-AS1 expression and survival rate and clinicopathological parameters were analyzed. Bioinformatics analysis, methylated RNA immunoprecipitation (meRIP), RNA pull-down and RNA-immunoprecipitation (RIP) assay were used to investigate the molecular regulation mechanism of THAP7-AS1. Cell proliferation, migration, invasion and tumorigenesis of SPC-A-1 and NCI-H1299 cells were determined by MTS, colony-formation, scratch, Transwell and xenotransplantation in vivo, respectively. Expression levels of phosphoinositide 3-kinase/protein kenase B (PI3K/AKT) signal pathway related protein were detected by Western blot.@*RESULTS@#Expression levels of THAP7-AS1 were higher in lung cancer tissues and cell lines (P<0.05). THAP7-AS1 has certain diagnostic value in lung cancer [area under the curve (AUC)=0.737], and its expression associated with overall survival rate, tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). METTL3-mediated m6A modification enhanced THAP7-AS1 expression. The cell proliferation, migration, invasion and the volume and mass of transplanted tumor were all higher in the THAP7-AS1 group compared with the NC group and sh-NC group of SPC-A-1 and NCI-H1299 cells, while the cell proliferation, migration and invasion were lower in the sh-THAP7-AS1 group (P<0.05). THAP7-AS1 binds specifically to Cullin 4B (CUL4B). The cell proliferation, migration, invasion, and expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD), phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) were higher in the THAP7-AS1 group compared with the Vector group of SPC-A-1 and NCI-H1299 cells (P<0.05).@*CONCLUSIONS@#LncRNA THAP7-AS1 is stably expressed through m6A modification mediated by METTL3, and combines with CUL4B to activate PI3K/AKT signal pathway, which promotes the occurrence and development of lung cancer.


Subject(s)
Humans , Lung Neoplasms/pathology , RNA, Long Noncoding/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Up-Regulation , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Methyltransferases/metabolism , Cullin Proteins/genetics
6.
Chinese Journal of Lung Cancer ; (12): 934-942, 2024.
Article in Chinese | WPRIM | ID: wpr-1010101

ABSTRACT

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently the first-line standard of care for patients with non-small cell lung cancer (NSCLC) that harbor EGFR mutations. Nevertheless, resistance to EGFR-TKIs is inevitable. In recent years, although immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm in advanced NSCLC without driver mutation, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Compared with wild-type tumors, tumors with EGFR mutations show more heterogeneity in the expression level of programmed cell death ligand 1 (PD-L1), tumor mutational burden (TMB), and other tumor microenvironment (TME) characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In this review, we summarized the clinical data with regard to the efficacy of ICIs in patients with EGFR-mutated NSCLC and deciphered the unique TME in EGFR-mutated NSCLC.
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Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , ErbB Receptors/metabolism , Immunotherapy , Mutation , B7-H1 Antigen/genetics , Protein Kinase Inhibitors/pharmacology , Tumor Microenvironment
7.
Chinese Journal of Lung Cancer ; (12): 943-949, 2024.
Article in Chinese | WPRIM | ID: wpr-1010102

ABSTRACT

So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.
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Subject(s)
Humans , Lung Neoplasms/genetics , Clinical Relevance , Evolution, Molecular , Mutation , Tumor Microenvironment
8.
Chinese Journal of Lung Cancer ; (12): 950-956, 2024.
Article in Chinese | WPRIM | ID: wpr-1010103

ABSTRACT

Due to the advancement of 16S rRNA sequencing technology, the lower respiratory tract microbiota, which was considered non-existent, has been revealed. The correlation between these microorganisms and diseases such as tumor has been a hot topic in recent years. As the bacteria in the surrounding can infiltrate the tumors, researchers have also begun to pay attention to the biological behavior of tumor bacteria and their interaction with tumors. In this review, we present the characteristic of the lower respiratory tract bacteria and summarize recent research findings on the relationship between these microbiota and lung cancer. On top of that, we also summarize the basic feature of bacteria in tumors and focus on the characteristic of the bacteria in lung cancer. The relationship between bacteria in lung cancer and tumor development is also been discussed. Finally, we review the potential clinical applications of bacterial communities in the lower respiratory tract and lung cancer, and summarize key points of sample collection, sequencing, and contamination control, hoping to provide new ideas for the screening and treatment of tumors.
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Subject(s)
Humans , Lung Neoplasms , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Microbiota , Respiratory System , Lung/microbiology
9.
Chinese Journal of Lung Cancer ; (12): 957-960, 2024.
Article in Chinese | WPRIM | ID: wpr-1010104

ABSTRACT

Ground-glass nodule (GGN) lung cancer often progresses slowly in clinical and there are few clinical studies on long-term follow-up of patients with operable GGN lung cancer treated with stereotactic body radiation therapy (SBRT). We present a successful case of GGN lung cancer treated with SBRT, but a new GGN was found in the lung adjacent to the SBRT target during follow-up. The nodule progressed rapidly and was confirmed as lung adenocarcinoma by surgical resection. No significant risk factors and related driving genes were found in molecular pathological findings and genetic tests. It deserves further study whether new GGN is related to the SBRT. This case suggests that the follow-up after SBRT should be vigilant against the occurrence of new rapidly progressive lung cancer in the target area and adjacent lung tissue.
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Subject(s)
Humans , Lung Neoplasms/pathology , Radiosurgery , Retrospective Studies , Adenocarcinoma of Lung/surgery , Lung/pathology
10.
Article in Chinese | WPRIM | ID: wpr-1010105

ABSTRACT

BACKGROUND@#Radiation therapy is one of the most common treatments for non-small cell lung cancer (NSCLC). However, the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients, and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge. This study aimed to identify the molecules associated with radioresistance in lung adenocarcinoma (LUAD), identified thyroid hormone receptor interactor 13 (TRIP13) as the main target initially, and explored whether TRIP13 is related to radioresistance in LUAD and the specific mechanism, with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic.@*METHODS@#Three datasets, GSE18842, GSE19188 and GSE33532, were selected from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (|log FC|>1.5, P<0.05) in each of the three datasets using the R 4.1.3 software, and then Venn diagram was used to find out the differentially expressed genes common to the three datasets. The screened differential genes were then subjected to protein-protein interaction (PPI) analysis and module analysis with the help of STRING online tool and Cytoscape software, and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database, and the TRIP13 gene was identified as the main molecule for subsequent studies. Subsequently, the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line, H292DR. The radioresistance of H292DR cells was verified using cell counting kit-8 (CCK-8) assay and clone formation assay. The expression levels of TRIP13 in H292 and H292DR cells were measured by Western blot. Small interfering RNA (siRNA) was used to silence the expression of TRIP13 in H292DR cells and Western blot assay was performed. The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing, followed by the detection of changes in the expression levels of proteins closely related to homologous recombination, such as ataxia telangiectasia mutated (ATM) protein.@*RESULTS@#Screening of multiple GEO datasets, validation of external datasets and survival analysis revealed that TRIP13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy. And the results of gene set enrichment analysis (GSEA) of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy. Experimentally, TRIP13 expression was found to be upregulated in H292DR, and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation.@*CONCLUSIONS@#TRIP13 is associated with poor prognosis in LUAD patients treated with radiation, possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms/radiotherapy , Adenocarcinoma of Lung/radiotherapy , Cell Count , Combined Modality Therapy , ATPases Associated with Diverse Cellular Activities , Cell Cycle Proteins
11.
Article in Chinese | WPRIM | ID: wpr-1010106

ABSTRACT

BACKGROUND@#Low-dose spiral computed tomography (LDCT) has been recommended for lung cancer screening in high-risk populations. However, evidence from Chinese populations was limited due to the different criteria for high-risk populations and the short-term follow-up period. This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013.@*METHODS@#A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017. Results of LDCT examination, and screen-detected cancer cases in all participants were obtained from the Reporting System of the Lung Cancer Screening Program. The newly-diagnosed cases and their vital status up to December 31, 2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics. Standardized incidence ratio (SIR) and 95%CI were calculated using the local population at ages of 40 or above as the reference. Proportions of early-stage cancer (stage 0-I), pathological types, and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations. Cox regression models were applied to evaluate the hazard ratio (HR) and 95%CI of LDCT screening with all-cause death of the lung cancer cases.@*RESULTS@#The crude and age-standardized incidence of lung cancer in screened population were 373.3 (95%CI: 343.1-406.1) and 70.3 per 100,000 person-years, respectively, with an SIR of 1.8 (95%CI: 1.6-1.9), which was observed to decrease with following-up time. The early-stage cancer accounted for 49.4% of all lung cancer cases derived from the screened population, significantly higher than 38.4% in cases from the non-screened population during the same period (P<0.05). The proportion of lung adenocarcinoma (40.7% vs 35.9%) and 5-year survival rate (53.7% vs 41.5%) were also significantly higher in the cases from the screened population (all P<0.05). LDCT screening was associated with 30% (HR=0.7, 95%CI: 0.6-0.8) reduced all-cause deaths of the cases.@*CONCLUSIONS@#The participants of the screening program are at high-risk of lung cancer. LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases, indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations.


Subject(s)
Adult , Humans , Lung Neoplasms/epidemiology , Tomography, X-Ray Computed , Early Detection of Cancer/methods , China/epidemiology , Tomography, Spiral Computed/methods , Mass Screening
12.
Article in Chinese | WPRIM | ID: wpr-1010107

ABSTRACT

BACKGROUND@#Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD.@*METHODS@#Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed.@*RESULTS@#SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1.@*CONCLUSIONS@#SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.


Subject(s)
Humans , Prognosis , Proteomics , Lung Neoplasms/genetics , Oncogenes , Adenocarcinoma of Lung/genetics , Biomarkers , Endonucleases/genetics
13.
Article in Chinese | WPRIM | ID: wpr-1010109

ABSTRACT

BACKGROUND@#Invasive mucinous adenocarcinoma (IMA) was a rare and specific type of lung adenocarcinoma, which was often characterized by fewer lymphatic metastases. Therefore, it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis (TNM) staging. So, this study aimed to develop Nomograms to predict outcomes of patients with pathologic N0 in resected IMA.@*METHODS@#According to the inclusion criteria and exclusion criteria, IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University (training cohort, n=78) and Ningbo No.2 Hospital (validation cohort, n=66) were reviewed between July 2012 and May 2017. The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established, and the performances of models were evaluated. Finally, the validation cohort data was put in for external validation.@*RESULTS@#Univariate analysis showed that pneumonic type, larger tumor size, mixed mucinous/non-mucinous component, and higher overall stage were significant influence factors of 5-year progression-free survival (PFS) and overall survival (OS). Multivariate analysis further indicated that type of imaging, tumor size, mucinous component were the independent prognostic factors for poor 5-year PFS and OS. Moreover, the 5-year PFS and OS rates were 62.82% and 75.64%, respectively. In subgroups, the survival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients, respectively. The C-index of Nomograms with 5-year PFS and OS were 0.815 (95%CI: 0.741-0.889) and 0.767 (95%CI: 0.669-0.865). The calibration curve and decision curve analysis (DCA) of both models showed good predictive performances in both cohorts.@*CONCLUSIONS@#The Nomograms based on clinicopathological characteristics in a certain extent, can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.


Subject(s)
Humans , Prognosis , Lung Neoplasms/pathology , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma of Lung/pathology , Neoplasm Staging , Lung/pathology , Retrospective Studies
14.
Article in Chinese | WPRIM | ID: wpr-1010110

ABSTRACT

BACKGROUND@#With the rise of multicolor flow cytometry, flow cytometry has become an important means to detect the immune microenvironment of lung cancer, but most of them are used to detect the proportion of cell subsets or the function of major cell subsets, and they cannot be detected at the same time. Therefore, a reliable 21-color flow cytometry protocol was established to detect the immune cell subsets in human non-small cell lung cancer (NSCLC) tumor tissues.@*METHODS@#Cell membrane surface antibodies cluster of differentiation (CD)45, CD3, CD19, CD4, CD8, programmed cell death 1 (PD-1), CD39, CD103, CD25, CD127, chemokine receptor 8 (CCR8), CD56, CD11c, human leukocyte antigen (HLA)-DR, CD38, CD27, CD69, CD62L, CD45RA, CCR7 and nucleic acid dye L/D were used to develop the protocol. Firstly, antibody titration experiments, voltage optimization, subtraction of one color staining and single color staining experiments were carried out for each antibody, and after the experimental conditions and detection schemes were determined, the feasibility of the scheme was verified by using peripheral blood mononuclear cells (PBMCs) specimens of six healthy adult volunteers. Tumor tissue samples from 6 NSCLC patients were tested and analyzed.@*RESULTS@#The established 21-color flow cytometry protocol was used to detect the tumor tissue samples of 6 NSCLC patients, and the proportion of each cell subset in lung cancer tissue, as well as the immunophenotype and differentiation of the main cell population, were analyzed.@*CONCLUSIONS@#The successfully established 21-color flow cytometry protocol is suitable for the detection of PBMCs and NSCLC tissue samples, which provides an effective new idea for monitoring the immune microenvironment status in lung cancer.


Subject(s)
Adult , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Flow Cytometry , Leukocytes, Mononuclear/pathology , Lung/pathology , Tumor Microenvironment
15.
Article in Chinese | WPRIM | ID: wpr-1010111

ABSTRACT

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.
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Subject(s)
Humans , Myeloid-Derived Suppressor Cells , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms/drug therapy , T-Lymphocytes , Immunotherapy , Tumor Microenvironment
16.
Article in Chinese | WPRIM | ID: wpr-1010112

ABSTRACT

V-Raf murine sarcoma viral oncogene homolog B (BRAF) alteration is one of the most essential driver genes of non-small cell lung cancer (NSCLC). BRAF encodes serine/threonine protein kinases, and its mutations typically lead to protein compositional activation, thereby activating the mitogen-activated protein kinase kinase (MEK) signaling pathway. A promising new approach for the treatment of mutated BRAF and/or downstream MEK may provide customized treatment opportunities for BRAF driven NSCLC patients. However, combination therapy is necessary to overcome the difficulties such as short duration of benefit, poor therapeutic effect of non-V600 BRAF mutations and susceptibility to drug resistance. This article reviewed the progress in structural characteristics, related signaling pathways, mutation types of BRAF gene, and the clinical pathological relationship between BRAF mutations and NSCLC, as well as the therapy, in order to provide more evidences for clinical doctors to make treatment decisions.
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Subject(s)
Animals , Mice , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Proto-Oncogene Proteins B-raf/genetics , Mutation , Mitogen-Activated Protein Kinase Kinases/therapeutic use , Protein Kinase Inhibitors/therapeutic use
17.
Journal of Chinese Physician ; (12): 43-47, 2024.
Article in Chinese | WPRIM | ID: wpr-1026059

ABSTRACT

Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.

18.
Journal of Chinese Physician ; (12): 478-480, 2024.
Article in Chinese | WPRIM | ID: wpr-1026123

ABSTRACT

Viruses are closely related to the occurrence of human diseases, and the infection of some viruses will lead to the occurrence and development of tumors, such as EB virus, hepatitis B virus, HPV virus, etc. On the contrary, some viruses can also be used for the treatment of tumors, such as oncolytic viruses. Lung cancer is a malignant tumor with the highest incidence rate and mortality rate in the world. In recent years, the relationship between virus and lung cancer has attracted more and more attention. Therefore, this article will review the mechanism and therapeutic impact of viruses on lung cancer.

19.
Article in Chinese | WPRIM | ID: wpr-1026308

ABSTRACT

Objective To observe the value of B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers.Methods A total of 74 lesions in 65 patients with lung cancers were prospectively enrolled,including 49 poorly differentiated lesions and 25 moderately or well differentiated ones,i.e.42 adenocarcinomas,14 squamous cell carcinomas and 18 small cell lung cancers(all poorly differentiated).B1 corrected T1 mapping was performed,ROI(ROI1 and ROI2)were delineated using 2 methods,and T1 values of different pathological types and differentiation degrees lung cancers were compared.The receiver operating characteristic(ROC)curves were drawn,and the areas under the curve(AUC)were calculated.Results Significant differences of T1 values were found among different pathological types of lung cancer(all P<0.05),as well as between small cell lung cancer and the rest 2 types of lung cancer(both P<0.05).There were significant differences of T1 values between poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)(both P<0.05).Taken ROI1 T1 value=1 524.21 ms as the cut-off value,the AUC of T1 value for distinguishing poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)was 0.698,with sensitivity of 64.50%and specificity of 76.00%.Taken ROI2 T1 value=1 630.68 ms as the cut-off value,the AUC of T1 value was 0.676,with sensitivity of 54.80%and specificity of 80.00%.Conclusion B1 corrected T1 mapping was helpful for distinguishing pathological types and differentiation degrees of lung cancers.

20.
Article in Chinese | WPRIM | ID: wpr-1026374

ABSTRACT

Conventional CT is an important imaging modality for the evaluation of lung cancer,but it has a single imaging modality.At present,multiparametric imaging techniques of spectral CT(such as virtual monoenergetic imaging,spectral attenuation curves,material decomposition images and material effective atomic number)are valuable in improving the detection rate of lesions,differentiating benign and malignant of lung nodes,assessing lymph node metastasis,pathological staging,efficacy and prognosis of lung cancer.Here,this article summarizes and reviews spectral CT imaging methods and the results of studies related to the above four techniques in lung cancer.

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