A new strategy for evaluating antitumor activity in vitro with time-dimensional characteristics of RTCA technology / 中国药理学通报

Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1

Prognostic Value and Immune Infiltration of Anoikis-related LncRNAs in Lung Adenocarcinoma / 肿瘤防治研究

Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.

Research progress of artificial intelligence in pathological subtypes classification and gene expression analysis of lung adenocarcinoma / 中国胸心血管外科临床杂志

@#Lung adenocarcinoma is a prevalent histological subtype of non-small cell lung cancer with different morphologic and molecular features that are critical for prognosis and treatment planning. In recent years, with the development of artificial intelligence technology, its application in the study of pathological subtypes and gene expression of lung adenocarcinoma has gained widespread attention. This paper reviews the research progress of machine learning and deep learning in pathological subtypes classification and gene expression analysis of lung adenocarcinoma, and some problems and challenges at the present stage are summarized and the future directions of artificial intelligence in lung adenocarcinoma research are foreseen.

High risk factors in images for infiltrating lung adenocarcinoma manifesting as peripheral ground-glass nodules / 中国胸心血管外科临床杂志

@#Objective     To explore the correlation between the imaging features of peripheral ground-glass pulmonary nodules and the invasion degree of lung adenocarcinoma, and the high risk factors for infiltrating lung adenocarcinoma under thin-slice CT, which provides some reference for clinicians to plan the surgical methods of pulmonary nodules before operation and to better communicate with patients, and assists in building a clinical predictive model for invasive adenocarcinoma. Methods    Clinical data of the patients with peripheral ground-glass pulmonary nodules (diameter≤3 cm) in thin-slice chest CT in the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were continuously collected. All patients underwent thin-slice CT scan and thoracoscopic surgery in our center. According to the pathological examination results, they were divided into two groups: an adenocarcinoma lesions before infiltration group, and an invasive lung adenocarcinoma group. The thin-slice CT imaging parameters of pulmonary nodules were collected. The nodular diameter, mean CT value, consolidation tumor ratio (CTR), nodular shape, vacuolar sign, bronchial air sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign and other clinical data were collected. Univariate and multivariate analyses were conducted to analyze the independent risk factors for the infiltrating lung adenocarcinoma, and to analyze the threshold value and efficacy of each factor for the identification of infiltrating lung adenocarcinoma. Results     Finally 190 patients were enrolled. There were 110 patients in the adenocarcinoma lesions before infiltration group, including 21 males and 89 females with a mean age of 53.57±10.90 years, and 80 patients in the invasive lung adenocarcinoma group, including 31 males and 49 females with a mean age of 56.45±11.30 years. There was a statistical difference in the mean CT value, nodular diameter, CTR, gender, smoking, nodular type, nodular shape, vacuolar sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign between the two groups (P<0.05). However, there was no statistical difference between the two groups in age (P=0.081), lesion site (P=0.675), and bronchial air sign (P=0.051). Multiple logistic regression analysis showed that nodular diameter, mean CT value, CTR and lobulation sign were independent risk factors for differentiating preinvasive adenocarcinoma from invasive adenocarcinoma. At the same time, the threshold value was calculated by Youden index, indicating that the CTR was 0.45, the nodal diameter was 10.5 mm and the mean CT value was –452 Hu. Conclusion     In the peripheral ground-glass pulmonary nodules, according to the patient's CT imaging features, such as mixed ground-glass nodules, irregular shapes, vacuoles, short burrs, clear boundaries, pleural indentations, and vascular clusters, have a certain reference value in the discrimination of the invasion degree of ground-glass pulmonary nodules. At the same time, it is found in this research that peripheral ground-glass pulmonary nodules with diameter greater than 10.5 mm, CT value greater than –452 Hu, CTR greater than 0.45 and lobulation sign are more likely to be infiltrating lung adenocarcinoma.

A predictive model of lymph node metastasis after thoracoscopic surgery for lung adenocarcinoma with a diameter≤3 cm / 中国胸心血管外科临床杂志

@#Objective    To predict the probability of lymph node metastasis after thoracoscopic surgery in patients with lung adenocarcinoma based on nomogram. Methods    We analyzed the clinical data of the patients with lung adenocarcinoma treated in the department of thoracic surgery of our hospital from June 2018 to May 2021. The patients were randomly divided into a training group and a validation group. The variables that may affect the lymph node metastasis of lung adenocarcinoma were screened out by univariate logistic regression, and then the clinical prediction model was constructed by multivariate logistic regression. The nomogram was used to show the model visually, the receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve to evaluate the calibration degree and practicability of the model. Results    Finally 249 patients were collected, including 117 males aged 53.15±13.95 years and 132 females aged 47.36±13.10 years. There were 180 patients in the training group, and 69 patients in the validation group. There was a significant correlation between the 6 clinicopathological characteristics and lymph node metastasis of lung adenocarcinoma in the univariate logistic regression. The area under the ROC curve in the training group was 0.863, suggesting the ability to distinguish lymph node metastasis, which was confirmed in the validation group (area under the ROC curve was 0.847). The nomogram and clinical decision curve also performed well in the follow-up analysis, which proved its potential clinical value. Conclusion    This study provides a nomogram combined with clinicopathological characteristics, which can be used to predict the risk of lymph node metastasis in patients with lung adenocarcinoma with a diameter≤3 cm.

Invasiveness assessment by CT quantitative and qualitative features of lung cancers manifesting ground-glass nodules in 555 patients: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective     To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. Methods    The patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results     A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion     The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.

Effect of ANKRD49 on migration of human lung adenocarcinoma cells and its mechanism / 中国生物制品学杂志

@#Objective To study the effect of ankyrin repeat domain 49(ANKRD49)on the migration of human lung adenocarcinoma cell line NCI-H1299 and its mechanism.Methods NCI-H1299 cells were infected with lentivirus vector carrying ANKRD49 gene and shRNA targeting ANKRD49 to construct the cell models stably overexpressing and knocking down ANKRD49. Meanwhile,the control cell models infected with empty lentivirus vector and lentivirus vector with scramble sequences were constructed respectively. The expression levels of ANKRD49 mRNA and protein were detected by real-time fluorescence quantitative PCR and Western blot. The effect of ANKRD49 on cell migration was measured by scratch test. The mRNA and protein levels of matrix metalloproteinase(MMP)-2/9 and tissue inhibitor of metalloproteinase(TIMP)-1/2 were detected by real-time fluorescence quantitative PCR and Western blot. The protein expression levels of p65,p-p65,IκBα and p-IκBα were detected by Western blot.Results The levels of ANKRD49 mRNA and protein in the ANKRD49 overexpression group were significantly higher than those in the control group(t = 70. 02 and 45. 68,respectively,each P < 0. 001). Compared with the control group,the migration ability of cells in the ANKRD49 overexpression group significantly increased at 24 h and 48 h(t = 5. 343 and 3. 282,P = 0. 005 9 and 0. 030 4,respectively);The mRNA transcription levels and protein expression levels of MMP-2 and MMP-9 significantly increased(t = 9. 304 and 6. 193,P =0. 000 7 and 0. 003 5,respectively),while the mRNA and protein expression of TIMP-1 and TIMP-2 decreased significantly(t = 3. 858 and 3. 517,P = 0. 018 2 and 0. 024 5,respectively),and the values of MMP-2/TIMP-1 and MMP-9/TIMP-2 significantly increased(t = 17. 7 and 9. 682,P < 0. 001 and < 0. 01,respectively);The expression of p-p65 and pIκBα significantly increased,the total protein levels of p65 and IκBα showed no obvious change,and the values of p-p65/p65 and p-IκBα/IκBα significantly increased(t = 3. 962 and 5. 370,P = 0. 016 7 and 0. 005 8,respectively). However,knocking down of ANKRD49 presented the opposite results.Conclusion ANKRD49 promotes the migration of NCI-H1299cells by enhan-cing the expression of MMP-2/9,the values of MMP-9/TIMP-1 and MMP-2/TIMP-2 via activating NF-κB/p65 signa-ling pathway.

Activation of CTHRC1 by HOXB9 Promotes Angiogenesis through Fatty Acid Metabolism in Lung Adenocarcinoma

Abstract Background: CTHRC1 is highly expressed in various cancers. Objectives: The aim of the study was to study the role of CTHRC1 played in lung adenocarcinoma (LUAD) development and its underlying biological functions. Methods: Enriched pathways and upstream transcription factors of CTHRC1 were explored by bioinformatics analysis. Dual-luciferase assay and Chromatin immunoprecipitation assay were used to verify the binding relationship between CTHRC1 and HOXB9. CCK-8 was utilized to detect cell viability. Expression levels of CTHRC1, HOXB9, and angiogenesis-related genes were assessed by quantitative real time-polymerase chain reaction. Angiogenesis assay was used to detect angiogenesis ability. Quantitative analysis of metabolites were used to detect the accumulation of neutral lipids, the levels of free fatty acids (FAs), and glycerol. Western blot was conducted to measure expression of metabolic enzymes of FA. Results: CTHRC1 was enriched in FA metabolic pathway, which was positively correlated and bound with HOXB9. CTHRC1 and HOXB9 expression was remarkably up-regulated in LUAD cells. Overexpression of CTHRC1 promoted FA metabolic pathway and angiogenesis, and FA inhibitor Orlistat restored it to NC group level. Meanwhile, CTHRC1 affected LUAD angiogenesis by activating HOXB9 to regulate FA metabolism. Conclusions: This study found that activation of CTHRC1 by HOXB9 induces angiogenesis by mediating FA metabolism. CTHRC1 may be a potential target for LUAD diagnosis.

TTYH3 is a prognostic biomarker and associates with immune cell infiltrations of lung adenocarcinoma / TTYH3 es un biomarcador pronóstico y se asocia con infiltraciones de células inmunitarias del adenocarcinoma de pulmón

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

Effect of SMAC Gene on Sensitivity of Lung Adenocarcinoma Cells to Paclitaxel and Cell Viability Based on caspase-3/Bcl-2/Bax Signaling Pathway / 肿瘤防治研究

Objective To investigate the effect of the SMAC gene on paclitaxel sensitivity and cellular activity in lung adenocarcinoma cells based on the caspase-3/Bcl-2/Bax signaling pathway. Methods A paclitaxel-resistant cell line A549/Taxol was established for lung adenocarcinoma, and the cells were divided into four following groups: pcDNA-NC (transfected with pcDNA-NC blank vector), pcDNA-SMAC (transfected with pcDNA-SMAC vector), siRNA-NC (transfected with siRNA-NC empty virus vector), and siRNA-SMAC groups (transfected with siRNA-SMAC lentiviral vector). The SMAC mRNA expression in cells was detected by qRT-PCR; cell sensitivity was detected by MTT; cell proliferation ability was detected by cloning assay; cell invasion ability was detected by Transwell; apoptosis ability was detected by flow cytometry assay; and caspase-3, Bcl-2 and Bax protein expression in cells were detected by Western blot analysis. Results The SMAC mRNA expression was significantly lower in A549 cells compared with BEAS-2B cells (P < 0.05). The SMAC mRNA expression was significantly higher in the pcDNA-SMAC group than that in the pcDNA-NC group cells (P < 0.05). The SMAC mRNA expression was significantly lower in the cells of the siRNA-SMAC group (P < 0.05) than that in the siRNA-NC group. The SMAC mRNA expression was significantly lower in the cells of the siRNA-SMAC group (P < 0.05) than in the siRNA-NC group. Compared with the pcDNA-NC group, the cell IC50, cell clone number, cell invasion ability, and Bcl-2 protein and Bcl-2/Bax ratio were significantly lower in the pcDNA-SMAC group, the cell resistance index reversal was 2.51-fold, and the apoptosis ability and caspase-3, as well as Bax protein expression, were significantly higher (P < 0.05). Compared with the siRNA-NC group, cell IC50, cell clone number, cell invasion ability, and Bcl-2 protein and Bcl-2/Bax ratio were significantly higher in the siRNA-SMAC group, and apoptosis ability and caspase-3 and Bax protein expression were significantly lower (P < 0.05). Conclusion High expression of SMAC increases paclitaxel sensitivity, inhibits cell growth and invasion, promotes apoptosis in lung adenocarcinoma cells, and has a regulatory effect on the caspase-3/Bcl-2/Bax signaling pathway.

miR-9500 Regulates Migration and Invasion of Lung Adenocarcinoma Cells by Targeting SMAD2 / 肿瘤防治研究

Objective To explore the molecular mechanism underlying miR-9500 regulating the migration and invasion of lung adenocarcinoma cells by targeting SMAD2. Methods The core target genes of miR-9500 were screened out by bioinformatics analysis, and their GO function analysis, KEGG signaling pathway enrichment, and survival analysis were performed. The targeted binding sites between miR-9500 and SMAD2 were predicted, and the direct targeting relationship between miR-9500 and SMAD2 was verified by dual-luciferase reporter assay. qRT-PCR and Western blot were used to assess the effect of miR-9500 on the mRNA and protein expression levels of SMAD2. Wound healing assay, Transwell assay, and Matrigel invasion assay were used to determine the effect of miR-9500 on the migration and invasion of lung adenocarcinoma cells. Results The core target genes of miR-9500 were mainly enriched in the cancer pathway, TGF-β signaling pathway, and focal adhesion. However, only the expression levels of VAMP2, SMAD2, and RXRA among the top 10 core target genes were significantly correlated with the overall survival of patients with lung adenocarcinoma. miR-9500 targeted SMAD2 and down-regulated the expression levels of SMAD2, and overexpression of miR-9500 significantly inhibited the migration and invasion of lung adenocarcinoma cells and markedly decreased the expression levels of MMP2 and MMP9. Conclusion miR-9500 can inhibit the migration and invasion of lung adenocarcinoma cells by targeting SMAD2, which may play an important role in the tumorigenesis and development of lung adenocarcinoma as a tumor suppressor.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma / 中国医学科学杂志(英文版)

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

Research progress on the characteristics and rapid diagnostic tools of early lung adenocarcinoma subtypes / 中国胸心血管外科临床杂志

@#Lung adenocarcinoma has become the most common type of lung cancer. According to the 2015 World Health Organization histological classification of lung cancer, invasive lung adenocarcinoma can be divided into 5 subtypes: lepidic, acinar, papillary, solid, and micropapillary. Relevant studies have shown that the local lobectomy or sublobectomy is sufficient for early lepidic predominant adenocarcinoma, while lobectomy should be recommended for tumors containing micropapillary and solid ingredients (≥5%). Currently, the percentage of micropapillary and solid components diagnosed by frozen pathological examination is 65.7%, and the accuracy of diagnosis is limited. Therefore, to improve the accuracy of diagnosis, it is necessary to seek new methods and techniques. This paper summarized the characteristics and rapid diagnosis tools of early lung adenocarcinoma subtypes.

Clinical observation of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of EGFR-TKI acquired resistant advanced lung adenocarcinoma / 中国药房

OBJECTIVE To compare the short-term therapeutic effect and safety of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） acquired resistant advanced lung adenocarcinoma. METHODS The information of 84 patients with EGFR-TKI acquired resistant advanced lung adenocarcinoma in the Third People’s Hospital of Chengdu was analyzed retrospectively during Jun. 2019-Oct. 2021. The patients were divided into chemotherapy group （32 cases）， anlotinib combined chemotherapy group （24 cases） and bevacizumab combined chemotherapy group （28 cases）. Patients in the chemotherapy group were given Pemetrexed disodium for injection and Carboplatin injection， and symptomatic treatment was given for adverse reactions. On the first day of chemotherapy， patients in the anlotinib combined chemotherapy group received Anlotinib hydrochloride capsules 10 mg orally， once a day， for 14 consecutive days and 7 days of discontinuation， based on the treatment of the chemotherapy group. Patients in the bevacizumab combined chemotherapy group were given Bevacizumab injection of 15 mg/kg intravenously 1 day before chemotherapy， based on the treatment of the chemotherapy group. Three groups of patients were treated for a total of four cycles， with one cycle every three weeks. The overall response rate （ORR）， disease control rate （DCR）， median progression-free survival （mPFS）， and the changes of serum tumor markers were compared among three groups before and after treatment； meanwhile， the occurrence of adverse drug reactions was recorded， and the 1-year survival rate was followed up. RESULTS After 4 treatment cycles， ORR and DCR of bevacizumab combined chemotherapy group and anlotinib combined chemotherapy group were higher than chemotherapy group （P＜0.05）； mPFS of the two groups were significantly longer than chemotherapy group， and DCR of anlotinib combined chemotherapy group was significantly higher than bevacizumab combined chemotherapy group （P＜0.05）. After 4 treatment cycles， the serum levels of tumor markers in three groups were significantly lower than before treatment， and both combined chemotherapy groups were significantly lower than chemotherapy group （P＜0.05）. There was no statistically significant difference in the incidence of adverse reactions such as nausea， vomiting， bone marrow suppression， and 1-year survival rate among the three groups of patients （P＞0.05）. CONCLUSIONS Bevacizumab and anlotinib combined with chemotherapy drug are effective and safe in the treatment of advanced lung adenocarcinoma with acquired EGFR-TKI resistance.

Research progress on the correlation between imaging characteristics and pathological invasion degree of early lung adenocarcinoma / 中国胸心血管外科临床杂志

@#With the development of multi-slice spiral computed tomography (CT) technology and the popularization of low-dose spiral CT screening, more and more adenocarcinomas presenting ground-glass nodule (GGN) are found. Pathological invasiveness is one of the important factors affecting the choice of treatment strategy and prognosis of patients with early lung adenocarcinoma. Imaging features have attracted wide attention due to their unique advantages in predicting the pathologic invasiveness of early lung adenocarcinoma. The imaging characteristics of GGN can be used to predict the pathologic invasiveness of lung adenocarcinoma and provide evidence for clinical decisions. However, the imaging parameters and numerical values for predicting pathologic invasiveness are still controversial, which will be reviewed in this paper.

Efficacy of systematic versus lobe-specific lymph node dissection in the treatment of clinicalⅠA stage lung adenocarcinoma: A propensity score matching study in a single center / 中国胸心血管外科临床杂志

@#Objective     To analyze the effects of systematic lymph node dissection (SLND) and lobe-specific lymph node dissection (L-SND) on perioperative and long-term outcomes of patients with clinicalⅠA (cⅠA) stage lung adenocarcinoma. Methods     A retrospective analysis was done on the patients with cⅠA stage lung adenocarcinoma who received thoracoscopic radical resection admitted to the Affiliated Hospital of Qingdao University from January 2013 to August 2016. Propensity score matching was conducted to eliminate the biases. The recurrence-free survival was compared between the two groups after matching. Perioperative parameters and postoperative complications were also analyzed. Results     A total of 725 patients were enrolled, including 252 males and 473 females, with a median age of 62.0 (31.0-69.0) years. There were 228 patients in the L-SND group and 497 patients in the SLND group. After matching, there were 211 patients in each group and no statistical difference in the incidence of postoperative complications (10.9% vs. 13.7%, P=0.374), identification of metastatic positive lymph nodes (12.3% vs. 9.0%, P=0.270), or recurrence-free survival (P=0.492) were found between two groups, whereas the operation time (163.9±39.4 min vs. 135.4±32.4 min, P<0.001), intraoperative blood loss [100.0 (20.0-800.0) mL vs. 100.0 (10.0-400.0) mL, P<0.001], intubation time [4.0 (1.0-18.0) d vs. 4.0 (1.0-9.0) d, P<0.001] and hospital stay (12.3±3.3 d vs. 10.8±2.4 d, P=0.003) in the SLND group were found to be significantly higher or longer than those in the L-SND group. Conclusion     L-SND has a similar efficiency to SLND in terms of postoperative complications, pathological lymph node metastasis, and recurrence-free survival, as well as significant advantages in reducing intraoperative blood loss, and shortening operation time, intubation time and length of hospital stay. Therefore, L-SND can be recommended to replace SLND as a method for lymph node resection in patients with cⅠA stage lung adenocarcinoma.

Intermittent EGFR-TKI Therapy is Associated with Durable Response in Advanced EGFR-Mutant NSCLC: A Case Report

@#Madam S, who diagnosed to have stage IV lung adenocarcinoma with exon 21 L858R point mutation (T3N2M1a) was admitted for massive pericardial effusion in April 2016. She was ECOG 4 on admission. Her ECOG improved to 1 after pericardial tapping and initiation of free sample erlotinib 100 mg daily. Repeated CT thorax post treatment showed the disease was partial responded. Due to financial constraints, she had never bought any EGFR-TKI. She was given a free sample of erlotinib intermittently for total of 12 months followed by intermittent afatinib supply for 2 years. Due to this limited supply, she took half doses of afatinib by cutting a 40 mg tablet once every few days to sustain the continuation of cancer treatment. No major side effects were observed and she remained ECOG 0 with good weight gain. Up to her last clinic visit in September 2021, her PFS was more than 5 years. Intermittent doses of EGFR-TKI may prolong PFS in patients with advanced EGFRm+ NSCLC who has limited treatment options.

Biological characteristics and clinical significance of cuproptosis-related genes in lung adenocarcinoma / 中国胸心血管外科临床杂志

@#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.

Risk factors of postoperative acute pain after thoracoscopic surgery for patients with early-stage lung adenocarcinoma / 中华胸心血管外科杂志

Objective:To improve the understanding of acute pain after thoracoscopic surgery in patients with early-stage lung adenocarcinoma, to analyze and screen out the independent risk factors that may induce acute postoperative pain. The patients' surgery experience may get improved through the corresponding timely and effective interventions.Methods:We retrospectively reviewed the clinical data of 204 patients with early-stage lung adenocarcinoma who were treated by a single medical team of our center from May 2021 to October 2021, and analyzed the assessment results of acute postoperative pain. Patients were grouped according to the general condition, past medical history, social and spiritual attributes, lesion characteristics, surgical approaches and anesthetic methods. Comparison of proportions of acute postoperative pain between the groups were made, and independent risk factors were identified.Results:A total of 84 males and 120 females were enrolled, with a mean age of(57.9±11.5)years old and a median operation time of 120(110, 145) min. No serious complication or perioperative death occurred in the whole group. Postoperative pain control failed in 76 cases(37.3%), 24 cases(11.8%) suffered from severe postoperative pain, and 33 cases(16.2%) required additional intramuscular injection of strong analgesics after surgery. Those who were younger than 60 years old, with a university degree or above, received two-incision surgery, operated for more than 2 h, received general anesthesia only, or in a state of depression, had significantly higher rates of postoperative acute pain, compared with their respective control groups( P<0.05). The independent risk factors for acute pain after thoracoscopic surgery included age( P=0.002), history of alcoholism( P=0.014), number of incisions( P=0.016), operation time( P=0.010), depression status( P=0.037) and enhanced anesthetic method( P=0.012). Conclusion:A large amount of patients with early-stage lung cancer suffered from acute pain after thoracoscopic surgery, which seriously affected their treatment experience and even quality of life. Young patients with a history of alcoholism and depression status were high-risk groups for postoperative acute pain. Applying Uniportal video-assisted thoracoscopic surgery, reducing the operation time as much as possible, and choosing enhanced analgesic anesthesia represented by epidural block combined with general anesthesia might be effective ways to reduce the probability of acute postoperative pain.