摘要
RESUMEN Los inhibidores de la tirosina quinasa han cambiado drásticamente la perspectiva clínica de los pacientes con cáncer de pulmón de células no pequeñas avanzado con mutaciones del receptor del factor de crecimiento epidérmico. Sin embargo, existen aún retos en el manejo de los pacientes con esta mutación en un escenario metastásico, como es la resistencia intrínseca y adquirida a inhibidores de tirosina quinasa. Se discutirán los últimos avances y nuevas estrategias en primera línea de tratamiento, resistencia a osimertinib y tratamiento en mutación, en el exón 20.
ABSTRACT Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.
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Objective To exploring the correlation between the expression level of serum carbohydrate antigen 211(CA211)and the number of natural killer(NK)cells and prognosis in non-small cell lung cancer(NSCLC)pa-tients.Methods 132 NSCLC patients admitted to the Affiliated Hospital of Hangzhou Normal University from June 2019 to July 2022 were selected as the test group,and 132 patients with benign lung lesions during the same period were selected as the control group.Data were collected from the laboratory to analyze the relationship between serum CA211 expression and NK cell count in NSCLC with clinical prognosis,as well as the related factors affecting the prognosis of NSCLC patients.Results The neutrophil to lymphocyte ratio(NLR)and serum CA211 expression in the test group were higher than those in the control group(P＜0.05),while the count of NK cells was less than that in the control group(P＜0.05);The expression level of serum CA211 in the test group was negatively cor-related with the count of NK cells(r=-0.405,P＜0.001);There were significant differences in lymph node metastasis and TNM staging among patients with different levels of serum CA211 expression and NK cell count(P＜0.05);The one-year survival rate of patients with low expression of CA211 was significantly higher than that of patients with high expression of CA211(P＜0.05),and the one-year survival rate of patients with high count of NK cells was higher than that of patients with low count of NK cells(P＜0.05);Lymph node metasta-sis,TNM staging and CA211 level were all risk factors affecting the prognosis of NSCLC patients(P＜0.05),while counting of NK cells was protective factor for the prognosis of NSCLC patients(P＜0.05).Conclusions The level of serum CA211 and the number of NK cells in NSCLC patients are closely related to pathological characteristics and clinical prognosis.
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Objective To investigate the impacts of cinobufotalin combined with docetaxel+cisplatin chemotherapy on the disease control and the level of vascular endothelial growth factor(VEGF)in serum of patients with non-small cell lung cancer.Methods Totally 70 patients with non-small cell lung cancer admitted to Zhejiang Veteran Hospital from March 2019 to March 2022 were included.They were randomly divided into combination group(cinobufotalin combined with docetaxel+cisplatin,n= 35)and control group(docetaxel+cisplatin chemotherapy alone,n=35).The disease control rates of two groups,serum VEGF level,carcinoembryonic antigen(CEA),cy-tokeratin 19(CK19)and carbohydrate antigen 125(CA125)were measured using ELISA;life quality of patients was evaluated with the KPS score;The adverse events between two groups were compared.Results The disease control rate in the combination group(33/35,94.29％)was higher than that that of control group(25/35,71.43％,)(P＜0.05).After treatment,the level of VEGF in both groups of patients decreased,and the KPS score increased(P＜0.05)especially in the combination group(P＜0.05).After treatment,the level of serum CEA,CA125,and CK19 of control group and combination group were obviously lower than those before treatment(P＜0.05),while those in the combination group were even lower(P＜0.05).The incidence of adverse events in the combination group(5/35,14.29％)was lower than that in the control group(13/35,37.14％)(P＜0.05).Conclusions Cinobufotalin combined with docetaxel+cisplatin chemotherapy as a potential new chemotherapy significantly reduces the level of VEGF and tumor biomarkers in serum factor,improves the life quality of patients.The combined therapy is proved tobe safe.
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Objective To explore the effects of prohibitin 2(PHB2)on sensitivity of non-small cell lung cancer cell line A549 to erlotinib(Erl)and its potential mechanisms.Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2.The effects of PHB2 inhibition on cell proliferation and apop-tosis induced by Erl were observed.The colocalization of microtuble-associated protein light chain 3 alpha(LC3)and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha(GFP-LC3)transfection.Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU)staining.Cell colony formation was evaluated by colony forming assay.Apoptotic index of A549 cells was evaluated by TUNEL.Western blot was used to measure the expressions of PHB2 and LC3Ⅱ.Mitochondrial transmembrane potential,cytochrome c and respiratory chain complexⅠ/Ⅱ/Ⅴactivity were analyzed by the commercially availa-ble kits.Results Compared with the siPHB2 and siCtrl+Erl group,the EdU-positive A549 cells and the number of cell colonies decreased significantly(P＜0.05),while the TUNEL-positive A549 cells increased significantly(P＜0.05)in the siPHB2+Erl group.In addition,compared with the siPHB2 and siCtrl+Erl group,mitochondrial transmembrane potential and respiratory chain complexⅠ/Ⅱ/Ⅴactivity decreased significantly(all P＜0.05)and the levels of cytochrome c increased in mitochondrial fractions(P＜0.05)and decreased in cytosolic fractions(P＜0.05)in the siPHB2+Erl group.Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.
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Objective To investigate the effect of Anlotinib on proliferation and apoptosis in non-small cell lung cancer(NSCLC)cells and its molecular mechanism.Methods Non-small cell lung cancer cell lines A549 and H1299 were incubated with Anlotinib,miR-16-5p agonist and/or PD-1 overexpression vector respectively.CCK-8 assay and EDU assay were applied to detect the proliferation.Flow cytometry was performed to detect the cell apop-tosis.The relative expression of miR-16-5 p in A549 and H1299 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).The relative protein expression of PD-1 in A549 and H1299 was detected by Western blot assay.The interaction between miR-16-5p and PD-1 was determined by dual luciferase reporter assay.Finally,A549 cell xenograft model was established to assess the effect of Anlotinib on tumor growth in vivo.Results Anlotinib significantly increased miR-16-5p expression and decreased PD-1 expression in A549 cells and H1299 cells,inhibited cell proliferation and promoted apoptosis in a dose-dependent manner(P＜0.05).The highly-expressed miR-16-5p inhibited proliferation and promoted cell apoptosis(P＜0.05).Also,miR-16-5p targeted at PD-1 and negatively regulated PD-1 expression.Knockdown of PD-1 inhibited proliferation and pro-moted cell apoptosis(P＜0.05).PD-1 over-expression reversed the Anlotinib-mediated pro-proliferation and anti-apoptosis of miR-16-5p in A549 cells and H1299 cells(P＜0.05).Anlotinib significantly reduced tumor growth in vivo(P＜0.05).Conclusions Anlotinib may inhibit cell proliferation,anti-apoptosis,and reduce tumor growth for NSCLC,which is involved in miR-16-5p/PD-1 axis.
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Objective To investigate the association between four single nucleotide polymorphisms(SNP)(rs9340 in MAPK1,rs14804 in NRAS,rs712 and rs7973450 in KRAS)in the 3'UTR of ERK1/2 signaling pathway-related genes and non-small cell lung cancer(NSCLC).Methods A total of 478 NSCLC patients and 480 healthy controls were enrolled in this study.Four SNPs were genotyped by using TaqMan assays.The association between the four SNPs and NSCLC was analyzed.Results The distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the non-small cell squamous cell carcinoma(SCC)group(P = 0.009),suggesting that the G allele of rs9340 may be a protective factor for non-small cell lung squamous cell carcinoma(OR = 0.67,95%CI:0.50～0.91).In addition,in the<50 years age group,the distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the NSCLC group(P = 5.07×10-4),indicating that the G allele of rs9340 may be a protective factor for NSCLC(OR = 0.46,95%CI:0.29～0.72).Conclusion The SNP rs9340 in MAPK1 may be associated with the risk of NSCLC.
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Objective To explore the diagnostic value of serum ficolin-3(FCN3)and collagen triple helix repeat containing-1(CTHRC1)in non-small cell lung cancer(NSCLC)and their relationship with clinicopathological characteristics.Methods From July 2021 to August 2022,73 patients with NSCLC who were admitted to the our Hospital were selected as the study group,and 55 healthy people who came to our hospital for physical examination were regarded as the control group.the serum levels of FCN3 and CTHRC1 were measured by enzyme-linked immunosorbent assay(ELISA);Pearson method was applied to analyze the correlation of serum FCN3 and CTHRC1 levels in NSCLC patients;Logistic regression analysis was applied to analyze the influencing factors of NSCLC;the diagnostic value of serum FCN3 and CTHRC1 levels on the occurrence of NSCLC was analyzed by the ROC curve.Results The levels of serum FCN3 and CTHRC1 in the study group were obviously higher than those in the control group(P＜0.05);the levels of serum FCN3 and CTHRC1 were correlated with the degree of cancer cell differentiation,TNM stage and lymph node metastasis in NSCLC patients(P＜0.05);Pearson method analysis showed that there was a positive correlation between serum FCN3 and CTHRC1 levels in NSCLC patients(r=0.258,P=0.028);Logistic regression analysis showed that serum FCN3 and CTHRC1 were the influencing factors of NSCLC(P＜0.05);the area under the ROC curve of serum FCN3 and CTHRC1 levels in diagnosis of NSCLC was 0.869 and 0.810,respectively,the area under the ROC curve of NSCLC was 0.881,which were better than those of serum FCN3 and CTHRC1.Conclusion The levels of serum FCN3 and CTHRC1 in patients with NSCLC increase,which are related to the degree of cancer cell differentiation,TNM stage and lymph node metastasis,they are risk factor for NSCLC,and the combination of the two is more valuable in diagnosis of NSCLC.
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Objective To investigate the relationship between serum micro RNA(miRNAs)-873 and micro RNA-138-5p expression and tumor immune microenvironment(TIME)and prognosis in patients with non-small cell lung cancer(NSCLC).Methods A total of 108 NSCLC patients(NSCLC group)and 65 healthy volunteers(control group)who were admitted to Ba'nan Hospital Affiliated to Chongqing Medical University from February 2019 to February 2021 were selected.Real-time quantitative fluorescence polymeric chain reaction(qRT-PCR)was used to detect the expression of miR-873 and miR-138-5p in serum,and multiple immunofluorescence staining was used to detect tumor immune microenvironment indicators.Regular follow-up was conducted after discharge.Pearson analyzed the correlation between the expression of miR-873 and miR-138-5p in serum and the TIME index,and Kaplan-Meier and COX proportional risk regression analyzed the relationship between miR-873 and miR-138-5p and the prognosis of NSCLC patients.Results Comparison with control group,the expressions of miR-873(1.02±0.23 vs 3.15±0.82)and miR-138-5p(1.21±0.26 vs 3.54±0.92)in serum of NSCLC group were decreased,and the differences were statistically significant(t=-25.426,-24.769,all P＜0.05).The expressions of serum miR-873 and miR-138-5p of patients with low-to-moderate differentiation in TNM stages Ⅲ to Ⅳ were lower than those with highly differentiated patients in TNM stages Ⅰ to Ⅱ(t=9.615,10.253;6.889,3.361,all P＜0.05).The expressions of miR-873 and miR-138-5p in serum were negatively correlated with the values of PD-1,PD-L1,CD4 and CD8 H(r=-0.418～-0.673,all P＜0.05).The OS survival rate of NSCLC patients with low expression of miR-873 and miR-138-5p was lower than that of those with high expression of miR-873 and miR-138-5p(Log-Rankχ2=4.724,5.607,P＜0.05).TNM stage Ⅲ～Ⅳ was a risk factor for poor prognosis in patients with NSCLC(P＜0.05),and miR-873 and miR-138-5p were protective factors(P＜0.05).Conclusion The expressions of miR-873 and miR-138-5p in serum of NSCLC patients are down-regulated,which is related to TIME and low survival rate.
摘要
Lung cancer is the malignant tumor with the highest incidence and mortality among the Chinese.Tumor node metastasis(TNM)staging established by the American Joint Committee on Cancer(AJCC)and International Union Against Cancer(UICC)is a commonly used criterion,but it still has limitations in judging the prognosis of non-small cell lung cancer(NSCLC)patients.With the advantages of real-time and convenient sampling,the immune score based on peripheral blood biomarkers have the ability to predict prognosis and efficacy of NSCLC patients,which have been developed and validated in clinical studies.However,clinical impleruentation of peripheral immune scores is still not widely in NSCLC patients.Therefore,this study introduces and evaluates the 6 peripheral immune scores and reviews the reseach progress of them in the treatment of NSCLC.
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Objective To investigate the biological function of long non-coding RNA(LncRNA)LINC01137 in immune escape of non-small cell lung cancer(NSCLC)cells and its potential regulatory mechanisms.Methods The blood samples of 24 healthy volunteers and 24 NSCLC patients were collected.The tumor tissues and paracancerous tissues of 24 NSCLC patients were collected,and the levels of LINC01137 were detected.The binding sites of LINC01137 and miR-22-3p were predicted by Starbase database and verified by the luciferase reporter gene analysis.A549 cells were transfected with exosomes derived from A549 cells and/or sh-LINC01137 interference sequence to detect cell proliferation and invasion.The supernatant of A549 cells were collected to culture CD8+T cells,and the levels of CD8+T cell exhaustion markers,including interfereron-γ(IFN-γ),tumor necrosis factor-α(TNF-α),granzyme B and interleukin-2(IL-2),and the percentage of PD-1+Tim3+CD8+T cells were detected.CD8+T cells were transfected with exosomes and/or miR-22-3p mimics to detect the protein level of PD-1.Results The expression of LINC01137 in tumor tissues of patients with NSCLC was increased compared with paracancerous tissues(3.357±0.548 vs 1.011±0.371),while the expression of LINC01137 in peripheral blood of patients with NSCLC was increased compared with healthy volunteers(3.216±0.342 vs 1.007±0.313),with statistically significant differences(t=-17.367,-17.147,all P<0.001).There was a positive correlation between the expression of LINC01137 in tumor tissue and peripheral blood(r=0.755,P<0.05).LINC01137 was significantly enriched in exosomes derived from A549 cells.Compared with Exo+sh-NC group,the cell viability(65.85%±4.71%vs 100.15%±11.93%)and cell invasion(21.46%±3.48%vs 43.12%±1.44%)in Exo+sh-LINC01137 group were decreased,and the differences were statistically significant(t=4.630,9.953,all P<0.01).The expression of LINC01137 in peripheral blood of NSCLC patients was negatively correlated with the percentage of CD8+T cells(r=-0.520,P<0.05).Compared with Exo+sh-NC group,the IFN-γ(3 865.31±543.85 pg/ml vs 1 786±105.98 pg/ml),TNF-α(4 631.93±510.71 pg/ml vs 1 973.24±379.62 pg/ml),Granzyme B(3 876.49±312.43 pg/ml vs 1 879.43±287.58 pg/ml),and IL-2 mRNA levels(3.286±0.437 vs 1.015±0.314)were increased,and the percentage of PD-1+Tim3+CD8+T cells(7.68%±2.18%vs 18.95%±3.21%)was decreased in Exo+sh-LINC01137 group,with statistical significances(t=-6.497,-7.237,-8.146,-7.310,5.021,all P<0.01).Our results showed that miR-22-3p was the target gene of LINC01137.Compared with Exo+NC mimic group,the level of PD-1 protein in Exo+miR-22-3p group(0.384±0.087 vs 1.003±0.147)was significantly decreased,and the difference was statistically significant(t=6.277,P<0.01).Conclusion The expression of LINC01137 was significantly up-regulated in tumor tissues and plasma of NSCLC patients.Exosomes LINC01137 derived NSCLC cell induces CD8+T cell exhaustion by targeting miR-22-3p and inhibiting its expression,and thus promoting NSCLC cell immune escape.
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Objective To investigate the relationship between the expression of claudin 10(CLDN10)and chondroitin sulfate proteoglycan 4(CSPG4)of tissue and clinicopathologic characteristics and prognosis in non-small cell lung cancer(NSCLC).Methods A total of 136 NSCLC patients who underwent surgery in Taizhou People's Hospital,Nanjing Medical University from January 2017 to April 2018 were randomly selected as the study subjects,and these subjects were grouped into survival group(n=63)and death group(n=69)based on follow-up outcomes(survival or death).Specimens of cancer tissue and adjacent tissues excised during surgery were collected from 136 patients.Real-time fluorescence quantitative PCR(RT-qPCR)was applied to detect the expression levels of CLDN10 and CSPG4 in cancer tissue and adjacent tissues.Based on the average expression levels of CLDN10 and CSPG4 in cancer tissues of NSCLC patients,they were grouped into CLDN10 high expression group(n=66),CLDN10 low expression group(n=70)and CSPG4 high expression group(n=71),CSPG4 low expression group(n=65).Multivariate COX regression analysis was used to determine the prognostic factors of NSCLC patients.Kaplan-Meier survival curve was applied to analyze the relationship between the expression levels of CLDN10 and CSPG4 in NSCLC patients and their prognosis.Results The expression level of CLDN10(0.96±0.25)in NSCLC tissues was lower than that in adjacent tissue(1.73±0.42),and the expression level of CSPG4 in NSCLC tissues(1.80±0.46)was higher than that in adjacent tissues(1.04±0.27),with statistical significance(t=18.372,16.617,all P<0.05).Compared with the survival group,the proportion of low undifferentiated,lymph node metastasis and CSPG4 expression of cancer tissues in the death group were higher,and the CLDN10 expression level of cancer tissues in the death group was lower,with statistical significance(t/χ2=8.463,7.423,11.696,6.426,all P<0.05).The five-year survival rate of the high expression group of CLDN10(58.46%)was higher than that of the low expression group(37.31%),and the five-year survival rate of the low expression group of CSPG4(55.56%)was higher than that of the high expression group(40.58%),and the differences were statistically significant(χ2=7.848,4.018,all P<0.05).Multivariate COX analysis results showed that low expression of CLDN10,high expression of CSPG4,low differentiation degree,and lymph node metastasis were all risk factors affecting the prognosis of NSCLC patients(HR=1.362,1.368,1.335,1.314,all P<0.05).Conclusion The expression level of CLDN10 was low and CSPG4 was high in cancer tissues of NSCLC patients,which was closely related to the development and prognosis of NSCLC.
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Non-small cell lung cancer(NSCLC)is a highly lethal malignant tumor that poses a serious threat to human health.Traditional methods for tumor diagnosis and treatment have many limitations.However,circulating tumor DNA(ctDNA)detection,a kind of liquid biopsy technology,has gained widespread attention in the field of NSCLC personalized therapy and monitoring due to its non-invasive,convenient,and comprehensive sensitivity.This article will review the latest research progress of ctDNA detection in the clinical diagnosis and treatment of NSCLC in recent years,including its applications in early screening,disease diagnosis,tumor mutation monitoring,treatment efficacy evaluation,and prognosis assessment.
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Objective To analyze the clinical data and head imaging features of perioperative acute ischemic stroke(POAIS)with non-small cell lung cancer(NSCLC)and to explore the possible risk factors and pathogeneses of it,and to provide evidence for the prevention and treatment of POAIS.Methods Data of patients with primary NSCLC who underwent lung resection and had POAIS was retrospectively collected,and the clinical data of patients with cerebral infarction of large artery atherosclerosis(LAA)and stroke of undetermined etiology(SUE)was compared.Results There were 25 NSCLC patients with POAIS,some of whom had no history of cardiovascular and cerebrovascular diseases,and the proportion was higher in SUE.The most common excision site was left upper lobe,especially in SUE.The pathological stage and type were mainly early stage and adenocarcinoma.Most patients developed POAIS within 7 days after surgery,and mainly mild to moderate.Middle cerebral artery was the main responsible vessel and most patients'cerebral infarction locations≥3.SUE was the most common type of Trial of Org 10172 in Acute Stroke Treatment(TOAST),followed by LAA type.Compared with SUE,more patients had a history of type 2 diabetes(P=0.006)and higher preoperative fasting glucose level(P=0.013)with LAA type.Conclusion Attention should be paid to the prevention of LAA type cerebral infarction in NSCLC patients with type 2 diabetes or preoperative high fasting glucose level,and antithrombotic regimen is selected according to different etiological mechanisms of POAIS.The formation of pulmonary vein thrombosis after lung resection should be prevented and paid attention to.
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Objective To investigate the significance of intratumoral and peritumoral radiomics models in predicting occult lymph node metastasis in stage T1 non-small cell lung cancer(NSCLC)and to compare the predictive accuracy in different peritumoral radiomics models.Methods The CT images and clinical data of 211 patients without lymph node metastasis on preoperative CT examination and pathologically confirmed NSCLC after surgery were collected.The radiomics features were derived from the three-dimensional volume of interest(VOI)of the intratumoral and peritumoral at 3-,5-,and 10-mm following lesion segmentation on CT images of each patient.The feature data of all nidus were radomly divide into training set and validation set with a ratio of 7︰3.The Pearson or Spearman correlation test was performed to remove redundancy.Dimensionality was reduced by the least absolute shrinkage and selection operator(LASSO)regression analysis.The linear combination of selected features and corresponding coefficients were used to construct the Radiomics score(Radscore).The clinical model and comprehensive model were constructed by logistic regression analysis.The conprehensive model was visualized with the nomogram,and its performance was evaluated.Results Among the peritumoral radiomics models,the peritumoral 5-mm model showed the best predictive efficacy[validation set,area under the curve(AUC)0.771].The comprehensive model containing Radscore,CT image features and CEA exhibited the best performance(validation set,AUC 0.850).Conclusion Intratumoral and peritumoral radiomics models perform efficiently in predicting occult lymph node metastasis in stage T1 NSCLC,and nomogram can effectively and noninvasively predict occult lymph node metastasis in NSCLC.
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Objective To explore the value of radiomics in differential diagnosis of small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).Methods Literature on the differential diagnosis of SCLC and NSCLC using radiomics was searched in Chinese and English databases.After literature screening and data extraction,Meta-DiSc1.4 and State16.0 SE software were used for analysis.Results A total of 910 patients were included in 8 studies.Meta-analysis results showed that the radiomics differential diag-nosis of SCLC and NSCLC had high co-sensitivity(Sen)and specificity(Spe),0.87[95%confidence interval(CI)0.83-0.91]and 0.88(95%CI 0.85-0.90),respectively.Meta-regression analysis showed that heterogeneity was not caused by feature extraction software type,joint machine learning,image pattern,brain metastasis,and sample size.Publication bias results didn't show any sig-nificant publication bias.Conclusion The radiomics method can differentiate and diagnose SCLC from NSCLC more accurately.When Matlab software is used to extract MRI image features combined with machine learning,and the sample size is large enough,the radiomics can differentiate and diagnose SCLC from NSCLC more accurately.
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Objective To analyze the immune regulation mechanism of C-MET expression in non-small cell lung cancer by transcriptome sequencing technology.Methods The C-MET expression of lung adenocarci-noma cell line(H1993)and lung squamous cell carcinoma cell line(EBC-1)with high C-MET expression was silenced using siRNA molecular interference technology.The differentially expressed genes(DEGs)before and after C-MET silencing were detected using transcriptome sequencing technology.The signal pathways and related genes of the immune microenvironment in which C-MET may participate in regulation were excavated through bioinformat-ics analysis.Finally,the co-culture technique of human immune cells with H1993 and EBC-1 was used to verify the effect of C-MET on immune factors such as INF-γ,INF-β and CXCL-10.Results We detected 505 DEGs in total using transcriptome sequencing.There were 38 differentially expressed genes in the C-MET regulation group before and after H1993,24 upregulated differentially expressed genes,and 14 downregulated differentially expressed genes,respectively.There are a total of 467 differentially expressed genes in the C-MET regulation group of EBC-1,347 upregulated differentially expressed genes,and 121 downregulated differentially expressed genes,respec-tively.KEGG analysis of differential genes suggested that C-MET expression might participate in the regulation of immune cell regulatory factors through the IL-17 signaling pathway,white blood cell differentiation,cytokine receptor activity,cell cycle,cytokine receptor activity,and cytokine-cytokine receptor interaction.The effect of C-MET on immune factor secretion was verified using the co-culture technique of lung cancer cells and human immune cells,and the results of Rt-qPCR assay suggested,the mRNA transcriptional level of INF-γ in PBMC co-cultured with the C-MET high expression group was 77 times that of the low expression group,and the mRNA transcriptional level of CXCL-10 was 1.6 times that of the low expression group.The mRNA transcriptional level of INF--β was twice as high as that of the low expression group.Conclusion C-MET expression may participate in the regulation of tumor surrounding immune microenvironment through IL-17 signaling pathway,leukocyte differen-tiation,and cytokine receptor activity pathway.
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Objective To investigate the effect and regulatory mechanism of autophagy related multifunc-tional protein p62/SQSTM1 on biological behavior in non-small cell lung cancer(NSCLC).Methods RT-qPCR was used to detect the expression of p62 in normal lung cells and NSCLC cells.CCK-8,wound-healing and Transwell assays were used to detect the effects of inhibition and promotion of p62 expression on the proliferation,migration and invasion in NSCLC cells.Western blotting was used to detect the effects of inhibition and promotion of p62 expression on the expression of apoptosis-related proteins(Bcl-2 and Bax)and autophagy-related proteins(ATG5 and Becline1)in NSCLC cells.A nude mouse transplantation tumor experiment was used to detect the effect of inhibiting p62 expression on the tumor volume and mass of NSCLC cells in vivo.Results Compared with that in normal lung cells,the expression level of p62 in A549 cells was the highest.Cell function experiments in vitro showed that inhibition of p62 expression reduced the abilities of proliferation,migration and invasion in A549 cells,and suppressed autophagy and induced apoptosis.Consistently,p62 overexpression has the opposite effects.In addi-tion,animal experiments in vivo showed that inhibition of p62 expression decreased the tumor volume and mass of tumor-bearing mice.Conclusion p62 could promote the growth of NSCLC A549 cell in vivo and in vitro by modu-lating autophagy.
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Objective To investigate the influence of the Janus kinase-signal transducer and transcription activator(JAK-STAT)signaling pathway mediated by Kruppel-like factor 14(KLF14)on the prognosis of non-small cell lung cancer(NSCLC).Methods From January 2018 to September 2019,NSCLC tissues from 80 patients and malignancy-free paracancerous tissues from 25 patients were collected.Medical follow-up ended in April 2023.Immunohistochemistry was used to detect the expression of KLF14 in tissues,and the patients were divided into a high-expression group and a low-expression group according to the median level of KLF14 expression.Over-expres-sion or knock-down of KLF14 and JAK1 was achieved by transfection of KLF14 and JAK1 overexpression plasmid in A549 cells and transfection of KLF14 and JAK1 specific short hairpin RNA(shKLF14 and shJAK1)in HCC827 cells.The proliferation activity of cells was analyzed by cell clone formation test.Transwell analyzed the migration and invasion of cells.Results As compared with the normal paracancerous tissues,the expression of KLF14 in NSCLC tissue decreased(P<0.001).The low expression of KLF14 was significantly correlated with tumor diameter of>3 cm,lymph node metastasis and clinical stage Ⅲ(P<0.05).There was a significant difference in the overall survival rate between the high KLF14 expression group and the low KLF14 expression group,and the patients with low KLF14 expression had poor prognosis(P = 0.039).After overexpression of KLF14,the proliferation ability of A549 cells and the number of migration and invasion of these cells decreased significantly(P<0.05);while after knock-down of KLF14,the proliferation ability of HCC827 cells and the number of migration,and invasion of these cells increased significantly(P<0.05).As compared with Vector + KLF14 group,the number of colonies,migration and invasion of A549 cells in JAK1 + KLF14 group increased significantly(P<0.05).As compared with shNC + shKLF14 group,the number of colonies,migration and invasion of HCC827 cells in shJAK1 + shKLF14 group decreased significantly(P<0.05).Conclusions Low expression of KLF14 is associated with poor overall survival in NSCLC patients.Up-regulation of KLF14 significantly inhibits the proliferation and metastasis of lung cancer cells in vitro,and its mechanism may be related to inhibition of the JAK-STAT signaling pathway.
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Objective To analyze and compare the clinical efficacy of CalliSpheres drug-eluting micro-spheres and blank microspheres in the treatment of advanced non-small cell lung cancer by bronchial arterial chemoembolization.Methods Fifty patients with advanced non-small cell lung cancer who had failed or relapsed after radiotherapy,chemotherapy,targeting and immunotherapy were collected and treated with super-selective bronchial artery chemoembolization.A retrospective analysis was conducted to compare the tumor response rate and survival between CalliSpheres drug-eluting and blank microspheres.Results The PR,ORR and DCR in the drug-eluted microsphere group were higher than those in the blank microsphere group,and there was a statistical difference in DCR between the two groups 1 month after surgery(χ2 = 4.08,P = 0.04).PD in the drug-eluted microsphere group was lower than that in the blank microsphere group.The CEA,CYF and SCC in the drug-eluted microsphere group after surgery were lower than those in the blank microsphere group,and the CEA,CYF and SCC in the two groups after surgery were lower than those before surgery,and there were statistical differences in CEA and CYF 1 month after surgery between the two groups.The PFS and OS in drug-eluted microsphere group were higher than those in blank microsphere group.Conclusion CalliSpheres drug-eluting microspheres could improve the effective rate of tumor treatment and prolong the survival time more effectively than the blank micro-spheres via arterial chemoembolization,providing reliable clinical practice basis for the treatment of advanced non-small cell lung cancer.
摘要
Objective To analyze the mutation of common driver genes in patients with non-small cell lung cancer(NSCLC)in eastern Henan Province.Methods A retrospective analysis was performed on 661 patients with NSCLC admitted to the First People's Hospital of Shangqiu city from March 2022 to July 2023.Five kinds of gene mutation detection kits(fluorescent PCR)were used for gene detection in all enrolled patients.The relationship between the clinical features and the status of each driver gene was analyzed by statistical methods.Results In the 661 patients with NSCLC,the mutation rates of EGFR,KRAS,ALK,ROS1,PIK3CA,BRAF,HER2,RET,MET14 and NRAS were 47.35%,9.68%,5.45%,1.82%,2.87%,1.82%,1.21%,0.91%,0.61%and 0%.Mutations in EGFR,ROS1 and HER2 were more likely to occur in women(P<0.05),while KRAS mutations were more common in men(P<0.05).The mutation rates of EGFR,KRAS and ALK in adenocarcinoma was significantly higher than that in squamous cell carcinoma and NSCLC.NOS(P<0.05),and the mutation rate of PIK3CA in NSCLC.NOS was the highest.The mutation rate of KRAS gene in stage Ⅰ+Ⅱ was significantly higher than that in stage Ⅲ+Ⅳ(P<0.05),and there was no significant correlation between other genes and clinical stage.Compared with smokers,the mutation rate of total driver gene was significantly higher in non-smokers(P<0.05).EGFR,ALK,PIK3CA,ROS1,BRAF and HER2 were more common in non-smokers(P<0.05),while KRAS gene was more common in smokers(P<0.05).The mutation rate of 10 driver genes in sediment cell block samples was 78.67%,and the detection rate was significantly higher than that in other types of samples(P<0.05).Conclusion Com-mon driver genes such as EGFR,KRAS and ALK are correlated with gender,pathological type,clinical stage and smoking.Qualified samples of sediment cells have obvious advantages for gene detection and could be widely pro-moted in patients.ARMS-PCR combined detection of 10 genes could be used as the preferred gene detection method for newly diagnosed and treated NSCLC patients.