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Objective:To investigate the effects of temozolomide combined with γ-fractional stereotactic radiotherapy on the expression of S100B and exosomal microRNA-330(miR-330) in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases.Methods:A total of 82 patients with NSCLC brain metastases from February 2018 to October 2020 were selected prospectively, and they were divided into the control group and the observation group by the random number table method, each with 41 patients. The control group received γ-fractional stereotactic radiotherapy, and the observation group received temozolomide on the basis of the control group. The therapeutic efficacy and prognosis of the two groups were compared, and the levels of serum myelin basic protein (MBP), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) levels, liver and kidney function indexes, serum S100B, carcinoembryonic antigen (CEA), exosomal miR-330 were compared between the two groups before and after the treatment. The neurologic function of the patients were evaluated by Mini Mental State Examination (MMSE) and National Institutes Health Stroke Scale (NIHSS).Results:The total remission rate in the observation group was higher than that in the control group: 65.85%(27/41) vs. 34.15%(14/41), there was statistical differences ( χ2 = 8.24, P<0.05), but the disease control rate between the two groups had no significant difference ( P>0.05). After the treatment, the levels of serum MBP, GFAP and NSE in the observation group were lower than those in the control group: (10.13 ± 2.07) μg/L vs. (14.39 ± 2.58) μg/L, (0.57 ± 0.12) μg/L vs. (0.75 ± 0.16) μg/L, (5.09 ± 1.16) μg/L vs. (7.17 ± 1.35) μg/L, there were statistical differences ( P<0.05). The levels alanine aminotransferase, blood urea nitrogen and serum creatinine after treatment between the two groups had no significant differences ( P>0.05). After the treatment, the NIHSS scores in the observation group was lower than that in the control group, MMSE scores was higher than that in the control group: (4.16 ± 0.52) scores vs. (4.73 ± 0.44) scores, (22.07 ± 2.51) scores vs. (20.68 ± 2.19) scores, there were statistical differences ( P<0.05). After treatment, the serum levels of S100B and CEA in the observation group were lower than those in the control group, and the expression of exosomal miR-330 was higher than that in the control group: (62.37 ± 10.54) mg/L vs. (68.05 ± 9.39) mg/L, (12.61 ± 2.05) μg/L vs.(14.08 ± 1.97) μg/L, 0.49 ± 0.12 vs. 0.42 ± 0.05, there were statistical differences ( P<0.05). The median survival time in the observation group was 14.6 months, while that in the control group was 11.50 months. There were no significant differences in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Treatment with temozolomide combined with γ-fractional stereotactic radiotherapy for NSCLC patients with brain metastases can improve the therapeutic efficacy, neurological function, inhibit the expression of serum S100B, CEA and exosomal miR-330, and prolong the survival time of patients.
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Immunotherapy,represented by immune checkpoint inhibitors(ICIs),has significantly changed the treat-ment strategy of non-small cell lung cancer(NSCLC)and has become an important therapy for all stages of NSCLC.However,there is an urgent need for further clarification regarding ICIs for elderly patients with advanced NSCLC.Treatment strategies for ICIs were guided by assessing survival data of elderly NSCLC patients included in clinical trials.We concluded that treatment regi-mens such as ICI monotherapy,dual immunotherapy,and ICIs combined with chemotherapy could be carried out in elderly NSCLC patients with a performance status(PS)score<2.Elderly NSCLC patients treated with ICIs could achieve similar benefits as younger patients and are generally well tolerated.However,as age increases(especially above 80 years),the efficacy decreased and the incidence of immune-related adverse events(irAEs)gradually increased.Therefore,ICIs should be carefully selected for advanced NSCLC patients at an advanced age.Compared to age,PS was a key factor causing patients to be excluded from ICIs and poorer survival outcomes.In conclusion,immunotherapy in elderly patients with advanced NSCLC is extremely challenging,and many issues still need further exploration in this field.
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AIM:To investigate the impact of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on the migration,invasion,and ferroptosis of non-small-cell lung cancer A549 cells.METHODS:The A549 cells were divided into control group,low-,medium-and high-dose(100,150 and 200 μg/mL)PHSTF groups,ferroptosis inhibitor liprox-statin-1(Lip-1)group,and high-dose PHSTF combined with Lip-1 group,each cultured in corresponding media.Cell via-bility was assessed using the CCK-8 assay,while cell migration and invasion abilities were determined through scratch and Transwell assays.Cell lipid peroxidation levels were measured using the glutathione(GSH)assay kit.RT-qPCR was em-ployed to assess the mRNA expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while Western blot was utilized to examine the protein expression of SLC7A11,GPX4,Kelch-like epichlorohy-drin-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1).RE-SULTS:Compared with control group,PHSTF significantly diminished the viability of A549 cells in a time-and dose-de-pendent manner(P＜0.01),and the cell migration and invasion were also reduced(P＜0.01),along with a significant de-crease in GSH level(P＜0.01).Treatment with PHSTF inhibited the mRNA and protein expression levels of ferroptosis-re-lated proteins,including SLC7A11 and GPX4(P＜0.01),suppressed the protein expression of Nrf2 and HO-1(P＜0.01),and enhanced the expression of Keap-1(P＜0.01).The Lip-1 partially restored the decrease in cell viability in-duced by PHSTF(P＜0.01),significantly up-regulated the protein expression levels of SLC7A11,GPX4,Nrf2 and HO-1,and suppressed the protein expression of Keap-1(P＜0.01).CONCLUSION:Total flavonoids of Pterocarya hupehen-sis Skan can inhibit the migration and invasion of non-small-cell lung cancer A549 cells,and induce the cell ferroptosis by regulating the Keap-1/Nrf2/HO-1 pathway.
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Objective:To investigate the value of peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and serum lactate dehydrogenase (LDH) levels for predicting the occurrence of radiation pneumonia (RP) in small cell lung cancer.Methods:A total of 84 patients with small cell lung cancer who received image-guided radiotherapy in Xuzhou Cancer Hospital between September 2019 and September 2022 were retrospectively analyzed. They were divided into an RP group ( n = 25) and a non-RP group ( n = 59) according to whether RP occurred. Peripheral blood NLR and PLR and serum LDH levels were compared between the two groups before and after radiotherapy. The receiver operating characteristic curve (ROC curve) was used to analyze the value of peripheral blood NLR, PLR, and serum LDH levels for the diagnosis of RP in small cell lung cancer. Results:Before radiotherapy, there were no significant differences in peripheral blood NLR and PLR between the two groups (both P > 0.05). After radiotherapy, peripheral blood NLR and PLR in the RP group were (3.39 ± 0.81) and (129.06 ± 24.90), respectively, which were significantly higher than those in the non-RP group [(2.54 ± 0.71), (104.76 ± 26.26), t = 3.61, 3.83, both P < 0.05]. The NLR (2.86 ± 0.30) and PLR (110.07 ± 10.05) were the lowest in patients with grade 2 RP and they were highest in patients with grade 4 RP [(4.49 ± 0.63), (168.88 ± 14.11)]. The grade of RP was positively correlated with peripheral blood NLR and PLR. The sensitivity of peripheral blood NLR in the diagnosis of RP was 88.0%, the specificity was 66.1%, and the area under the curve (AUC) was 0.791. The sensitivity of PLR in the diagnosis of RP was 48.0%, the specificity was 94.9%, and the AUC was 0.735. The sensitivity of NLR combined with PLR in the diagnosis of RP was 92.0%, the specificity was 59.3%, and the AUC was 0.801. There was no significant difference in serum LDH levels between the two groups before and after radiotherapy (both P > 0.05). Logistic regression analysis showed that NLR and PLR were risk factors for RP in patients with small cell lung cancer ( OR = 2.309, 1.037; 95% CI: 1.061-5.024, 1.004-1.071). Conclusion:In patients with small cell lung cancer who develop RP, peripheral blood NLR, and PLR are markedly elevated compared with those in patients who do not develop RP, and combined detection of peripheral blood NLR and PLR has a high value for early diagnosis of RP in patients with small cell lung cancer.
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Objective:To investigate the efficacy of tirellizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer and its effect on immune function and quality of life in patients.Methods:In this retrospective case-control study, we analyzed the clinical data of 104 patients with advanced (stages III and IV) non-small cell lung cancer who received treatment at Zhoushan Hospital between May 2021 and June 2022. These patients were divided into two groups: group A ( n = 52) and group B ( n = 52), based on the treatment methods utilized. Patients in group A received chemotherapy with gemcitabine plus cisplatin or pemetrexed plus cisplatin. Meanwhile, patients in group B were treated with tirellizumab combined with chemotherapy regimens of gemcitabine plus cisplatin or pemetrexed plus cisplatin, with 21 days as a treatment cycle. Both groups of patients received three cycles of treatment. The short-term efficacy was compared between the two groups. Additionally, serum levels of tumor markers, immune function indexes, quality of life score, and incidence of adverse reactions were compared between the two groups before and after treatment. Results:The short-term response rate in group B was significantly higher than that in group A [51.92% (27/52) vs. 32.69% (17/52), Z = 4.11, P < 0.001]. When compared with pretreatment levels, serum levels of tumor markers and the percentage of CD8 + cells decreased in both groups after treatment. Notably, the serum levels of tumor markers and the percentage of CD8 + cells were significantly lower in group B compared with group A (all P < 0.05). Moreover, after treatment, the percentage of CD4 + cells, the ratio of CD4 +/CD8 + cells, functional subscale, symptom subscale, and total score increased significantly compared with pretreatment levels (all P < 0.05) and were significantly higher in group B compared with those in group A (all P < 0.05). The incidence of adverse events in group B was significantly higher than that in group A [44.23% (23/52) vs. 21.15% (11/52), χ2 = 6.29, P = 0.012]. Conclusion:Tirelizumab combined with chemotherapy is effective for advanced non-small-cell lung cancer. The combined therapy can lower serum levels of tumor markers, restore immune function, and improve overall quality of life.
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Objective:To analyze the prognostic value of MET, Cyclin D1, and MET gene copy number (GCN) for non-small cell lung cancer (NSCLC).Methods:This study included 61 patients with NSCLC who received treatment at the Enze Hospital, Taizhou Enze Medical Center (Group) between January 2018 and June 2019. The expression levels of MET and Cyclin D1 were determined using immunohistochemistry. MET GCN was evaluated using a quantitative polymerase chain reaction. Clinicopathological characteristics were compared among patients with different expression levels of these proteins. The Spearman correlation coefficient was used to assess the relationship between MET, Cyclin D1, and MET GCN. The Kaplan-Meier method was used to analyze survival rates. Univariate and multivariate Cox regression analyses were conducted to investigate the correlation between MET, Cyclin D1, and MET GCN and survival rates.Results:Thirty-six cases (59.02%) tested positive for MET, which was mainly expressed in the cytoplasm and membrane. Similarly, 36 cases (59.02%) were positive for Cyclin D1, which was mainly expressed in the cytoplasm. Patients with MET ( χ2 = 6.89, P = 0.009) and MET/Cyclin D1 ( χ2 = 4.05, P = 0.004) had a high proportion of poorly differentiated histology. Moreover, patients with MET GCN ≥ 3 had a relatively high proportion of lymph node metastasis ( χ2 = 8.11, P = 0.004) and TNM stages III-IV ( χ2 = 3.91, P = 0.048). Furthermore, patients with MET GCN ≥ 3/Cyclin D1 also had a high proportion of lymph node metastasis ( χ2 = 6.73, P = 0.009). MET was significantly associated with MET GCN ( r = 0.39, P = 0.002) and Cyclin D1 ( r = 0.39, P = 0.002), while MET GCN was significantly associated with Cyclin D1 ( r = 0.30, P = 0.017). The median survival time of patients with and without MET was 24.0 and 32.5 months, respectively, while the median survival time of patients with MET GCN ≥ 3 and < 3 was 11.0 and 30.5 months, respectively. Multivariate analysis showed that TNM stages III-IV, positive expression of MET, and MET GCN ≥ 3 were significantly associated with a high risk of death. Conclusion:The positive expression of MET and MET GCN ≥ 3 may be adverse prognostic factors in patients with NSCLC. The activation of the MET/Cyclin D1 signaling pathway could potentially contribute to the development and progression of NSCLC.
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Objective:To investigate the effects of Kanglaite injection combined with chemotherapy on quality of life and myelosuppression in patients with non-small cell lung cancer (NSCLC).Methods:The clinical data of 60 patients with NSCLC who received treatment at Zhejiang Jinhua Guangfu Tumor Hospital from August 2018 to February 2022 were retrospectively analyzed. These patients were divided into an experimental group and a control group, with 30 patients in each group according to the treatment methods used. The patients in the experimental group received the Kanglaite injection in combination with chemotherapy using gemcitabine and cisplatin, whereas the patients in the control group were treated solely with chemotherapy with gemcitabine and cisplatin. The quality of life was evaluated using the Karnofsky Performance Status score. Before and after treatment, a comparison was made between the two groups in terms of Karnofsky Performance Status score, the incidence of adverse reactions (such as myelosuppression), and clinical efficacy.Results:After treatment, the disease control rate and objective response rate in the experimental group were 86.67% (26/30) and 60.00% (18/30), respectively, which were significantly higher than 60.00% (18/30) and 30.00% (9/30) in the control group ( χ2 = 4.18, 4.31, both P < 0.05). Prior to treatment, the Karnofsky Performance Status scores in the experimental and control groups were (70.68 ± 3.75) points and (70.29 ± 5.11) points ( t = 0.34, P = 0.790), respectively. After treatment, the Karnofsky Performance Status scores in the experimental group were significantly higher than those in the control group [(67.02 ± 5.87) points vs. (62.37 ± 3.59) points, t = -5.29, P < 0.05]. The incidence of adverse reactions in the experimental group was significantly higher than that in the control group [40.00% (12/30) vs. 36.67% (11/30), χ2 = 0.07, P = 0.790). Additionally, the incidence of myelosuppression in the experimental group was significantly lower than that in the control group [56.67% (17/30) vs. 86.67% (26/30), χ2 = 6.90, P = 0.030]. Conclusion:Compared with chemotherapy alone, Kanglaite injection combined with chemotherapy can effectively relieve the clinical symptoms of patients with advanced non-small cell lung cancer, leading to improved prognosis.
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Objective To compare the clinical efficacies of video-assisted thoracoscopic segmentectomy versus lobectomy for early-stage non-small cell lung cancer.Methods The clinical data of 234 patients with stage ⅠA non-small cell lung cancer and undergoing different surgical methods under video-assisted thoracoscopy admitted to Chongqing Dianjiang General Hospital were retrospectively analyzed,and the patients were divided into the lung segment group and the lung lobe group according to their surgical methods.The clinical characteristics of the patients in the two groups were balanced by a 1-to-1 ratio matching through the propensity score matching method,and each group finally included 63 cases.The perioperative indicators containing operation time,intraoperative blood loss,postoperative thoracic drainage tube indwelling time,thoracic drainage volumes 24 hours and 48 hours after operation and postoperative hospital stay were compared of patients between the two groups.The incidence of postoperative complications such as air leakage>6 days,pulmonary infection,atelectasis,hemoptysis,and hoarseness in the two groups was collected.Results There was no significant difference in the operation time,intraoperative blood loss,thoracic drainage volumes 24 hours and 48 hours after operation,postoperative thoracic drainage tube indwelling time or incidence of postoperative complications of patients between the two groups(P>0.05).The postoperative hospital stay of patients in the lung segment group was shorter than that in the lung lobe group,with statistically significant difference(P=0.003).Conclusion For patients with stage ⅠA non-small cell lung cancer,video-assisted thoracoscopic segmentectomy has similar perioperative efficacy to lobectomy,while segmentectomy has a more significant advantage in shortening the hospital stay.
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AIM:To investigate the relationship between the dynamic changes of Lymphocyte-to-monocytes ratios(LMR)before PD-1 inhibitor treat-ment and the efficacy and prognosis of PD-1 inhibi-tor treatment in patients with advanced non-small cell lung cancer(NSCLC).METHODS:The clinical case data of 83 patients with advanced non-small cell lung cancer admitted to the Cancer Hospital of Wuhu Second People's Hospital from June 2019 to July 2022 were retrospectively analyzed.The rou-tine blood LMR values of all patients before and af-ter treatment were collected,the cut-off value was calculated according to the ROC curve,and the LMR was divided into two groups:high and low be-fore treatment and after treatment.The differenc-es of ORR,DCR,PFS and OS among the patients in each group were analyzed and compared,and the value of LMR value and dynamic changes after treatment on the efficacy and prognosis of patients with PD-1 inhibitors in the treatment of NSCLC pa-tients was analyzed.RESULTS:According to the ROC curve,the critical value of LMR was 1.8,and the LMR was divided into the low LMR group at baseline(LMRB/S<1.8),the high LMR group at base-line(LMRB/S≥1.8)and the low LMR group after treatment(LMRafter<1.8)and the high LMR group af-ter treatment(LMRafter≥1.8).The ORR and DCR after immunotherapy in the high LMRB/S group were high-er than those in the low LMRB/S group(P=0.037;P= 0.0025).Among the patients with low LMRB/S be-fore treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group after treatment(P=0.005).Among the patients with high LMR before treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group(P=0.034).Kaplan-Meier analysis showed that PFS and OS were longer in the high LMRB/S group than in the low LMRB/S group before treat-ment.In the low LMRB/S group before treatment,PFS and OS were longer in patients with LMRafter≥1.8 than those with LMRafter<1.8(P=0.047;P=0.007).Multivariate Cox regression model analysis showed that high LMRB/S value before treatment was an in-dependent risk factor for PFS and OS in NSCLC pa-tients(P=0.006;P=0.033).CONCLUSION:High LMR value of patients before immunotherapy may im-prove the efficacy of PD-1 inhibitors,improve the prognosis of patients,and prolong the survival time.Moreover,the increase of LMR value after treatment may increase the efficacy of patients with low LMR before treatment and improve the prognosis of patients.
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Immune checkpoint inhibitors(ICIs)mainly including the CTL antigen 4(CTLA-4)and PD-1/PD-L1,which would offer a notable clinical benefit for non-small cell lung cancer(NSCLC)patients.By strengthening the antitumor immune re-sponse of the body,ICIs lead to immune-related adverse events(irAEs),including checkpoint inhibitor pneumitis(CIP).Although the clinical incidence of CIP is relatively low,some serious cases may prolong or terminate of immunotherapy,even life threateing.This article tries to summarize the clinical manifestations,pathological characteristics,biological mechanism,susceptible population,diagnosis and differential diagnosis,and integrated traditional Chinese and Western medicine treatment of CIP,in order to understand CIP more clearly.
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Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.
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Lung cancer is the malignant tumor with the highest incidence and death in the world,among which non-small cell lung cancer(NSCLC)accounts for the largest proportion.The BRAF gene is a proto-on-cogene associated with poor prognosis in NSCLC,represented by BRAF V600E mutations.In recent years,the diagnosis and treatment of NSCLC patients with BRAF V600E mutation has become the focus of accurate di-agnosis and treatment of lung cancer,especially its whole-course management.There are many related studies on targeting,immunotherapy and chemotherapy for patients with BRAF V600E mutation.This paper reviewed the relevant research progress at home and abroad.
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Objective To observe the levels of serum thymidine kinase 1(TK1)and secreted protein Dikkopf-1(DKK1)in patients with advanced non-small cell lung cancer(NSCLC),and analyze the relation-ship between serum TK1,DKK1 and the prognosis of NSCLC.Methods This study adopted a prospective co-hort study method,a total of 91 chemotherapy patients with advanced NSCLC admitted in Jinshan Branch of Shanghai Sixth People's Hospital from January 2020 to June 2021 were enrolled as the research objects.All patients received the detection of serum TK1 and DKK1 on admission,completed 4 chemotherapy cycles in Jinshan Branch of Shanghai Sixth People's Hospital and were followed up for 3 months.The disease remission rate was evaluated according to the relevant standards.The patients with complete remission and partial re-mission were included in the good prognosis group,and those with the stable and progressive lesions were in-cluded in the poor prognosis group.The levels of serum TK1 and DKK1 were compared between the two groups.Logistic regression was used to analyze the relationship between the levels of serum TK1 and DKK1 and the prognosis of patients with advanced NSCLC.Results Among 91 patients with advanced NSCLC who received chemotherapy,threre were 58 cases(63.74％)in the good prognosis group,and 33 cases(36.26％)in the poor prognosis group.The levels of serum carcinoembryonic antigen(CEA),TK1 and DKK1 in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).Logistic regression anal-ysis showed that the high levels of serum TK1 and DKK1 were the influencing factors of poor prognosis in pa-tients with advanced NSCLC(OR＞1,P＜0.05).The receiver operating characteristic curve was drawn,and the results showed that the area under the curve of serum TK1,DKK1 alone and combined for predicting the poor prognosis in patients with advanced NSCLC was＞0.700,all of which had certain predictive value,and the predictive value of the combined detection was the highest.Conclusion The abnormal increase of serum TK1 and DKK1 levels may indicate a high risk of poor prognosis in patients with advanced NSCLC.Early monito-ring of serum TK1 and DKK1 levels in patients has certain positive significance for predicting and evaluating the prognosis of patients.
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Objective To investigate the correlation between the expression of long non-coding ribonucleic acid growth arrest specific 5(lncRNA GAS5),phospholysine phosphohistidine inorganic pyrophosphate phos-phatase(LHPP)and epithelial-mesenchymal transition(EMT)in cancer tissues of patients with non-small cell lung cancer(NSCLC)and its clinical significance.Methods Cancer tissues and adjacent tissues of 90 patients with NSCLC who underwent surgical resection in the First Hospital Affiliated to Hebei North College from June 2018 to January 2020 were collected.The expressions of lncRNA GAS5,LHPP and EMT-associated pro-teins[E-calmodulin(E-Cad),N-calmodulin(N-Cad),and vimentin(VIM)]were detected by real-time fluores-cence quantitative polymerase chain reaction.The relationship between lncRNA GAS5 and LHPP mRNA and clinicopathological features in cancer tissues of NSCLC patients was analyzed,and the correlation between ln-cRNA GAS5 and LHPP mRNA and EMT-associated proteins expression in cancer tissues of NSCLC patients was analyzed by Pearson correlation.Kaplan-Meier method was used to plot the survival curves of NSCLC pa-tients with different lncRNA GAS5 and LHPP mRNA expressions,and multivariate Cox regression was used to analyze the prognostic factors of NSCLC patients.Results The expressions of lncRNA GAS5,LHPP mR-NA and E-Cad mRNA in cancer tissues of NSCLC patients were lower than those in adjacent tissues,while the expressions of N-Cad mRNA and VIM mRNA were higher than those in adjacent tissues,with statistical sig-nificance(P＜0.05).Pearson correlation analysis showed that lncRNA GAS5 in cancer tissues of NSCLC pa-tients was positively correlated with E-Cad mRNA expression(r=0.724,P＜0.001),and negatively correla-ted with N-Cad mRNA and VIM mRNA expression(r=-0.699,-0.689).P＜0.001);lncRNA GAS5 was positively correlated with LHPP mRNA expression(r=0.651,P＜0.001).The mRNA expressions of ln-cRNA GAS5 and LHPP in cancer tissues of NSCLC patients with different degrees of differentiation,tumor TNM stage and lymph node metastasis were significantly different(P＜0.05).Kaplan-Meier survival curve a-nalysis showed that the 3-year overall survival rate in the lncRNA GAS5 high expression group[68.18％(30/44)]was higher than that in the lncRNA GAS5 low expression group[36.96％(17/46)].The 3-year overall survival rate in the high LHPP mRNA expression group[67.39％(31/46)]was higher than that in the lowLHPP mRNA expression group[36.36％(16/44)],and the difference was statistically significant(x2=10.274,10.322,P＜0.05).Low differentiation,TNM stage Ⅲ and lymph node metastasis were independent risk factors for death in NSCLC patients,and lncRNA GAS5≥1.32 and LHPP mRNA≥1.12 were independ-ent protective factors(P＜0.05).Conclusion The low expression of lncRNA GAS5 and LHPP mRNA in cancer tissues of patients with NSCLC is related to EMT-associated proteins expression,differentiation de-gree,tumor TNM stage,lymph node metastasis and prognosis,and may become a new target for the diagnosis and treatment of NSCLC.
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Objective To investigate the role of microRNA(miR)-567 in the proliferation,migration and cell cycle of non-small cell lung cancer(NSCLC)through regulation of cyclin dependent kinase 8(CDK8)and its clinical relevance.Methods Tumor tissues and adjacent tissues of 40 NSCLC patients were collected,and the expressions of miR-567 and CDK8 were detected by real-time quantitative fluorescent PCR(qRT-PCR).miR-NC mimic,miR-567 mimic,oe-NC,and oe-CDK8 were transfected into A549 and H1975 cells.The ex-pressions of miR-567 and CDK8 were detected using qRT-PCR.Cell proliferation was detected by CCK-8 method,and cell migration was detected by Transwell assay.Cell cycle changes were detected by flow cytome-try.The targeting of miR-567 and CDK8 was detected by luciferase reporter gene assay.Results In the tumor tissues of NSCLC patients,the expression of miR-567 was decreased,while the expression of CDK8 was in-creased,and the two were negatively correlated(P＜0.05).In A549 and H1975 cells,miR-567 mimic group was compared with miR-NC mimic group,the expression of miR-567 was increased,the expression of CDK8 was decreased,the proliferation and migration levels of cells were decreased,the proportion of G1 phase was increased,and the proportion of S phase was decreased.The fluorescence intensity of miR-567 mimic group was lower than that of miR-NC mimic group in normal CDK8.miR-567 mimic+oe-CDK8 group was compared with miR-567 mimic+oe-NC group,the expression of CDK8 was increased,the proliferation and migration levels of cells were increased,the proportion of cells in G1 phase was decreased,and the proportion of cells in S phase was increased.Conclusion miR-567 can inhibit NSCLC proliferation and migration by targeting CDK8 expression and controlling tumor cell arrest in the S phase.
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Objective To analyze the therapeutic effect of anti-programmed death receptor 1(PD-1)/pro-grammed death ligand 1(PD-L1)and the characteristics of intestinal flora in patients with non-small cell lung cancer(NSCLC).Methods A total of 81 NSCLC patients admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to January 2022 were taken as the research object.According to the patients'immunotherapy response,the patients were divided into non-response group and response group.The differences in clinical data and intestinal flora distribution between the two groups were compared,and the correlation between PFS and intestinal flora a diversity index was analyzed by Spearman correlation.Results The proportion of smoking patients in response group was significantly lower than that in non-re-sponse group,and the difference was statistically significant(x2=4.648,P=0.031).Chao1 index,ACE index and shannon wiener index patients in non-response group were lower than those in response group,while Simpson diversity index was higher than that in response group,with statistical significance(P＜0.05).Chao1 index,ACE index and shannon wiener index were positively correlated with PFS(r=0.526,0.579 and 0.539,all P＜0.05),while Simpson diversity index was negatively correlated with PFS(r=-0.867,P＜0.001).The principal coordinate analysis was used to analyze the β diversity structure of intestinal flora.The first principal component contribution rate was 70.36％,and the second principal component contribution rate was 16.63％.Conclusion The diversity and distribution of intestinal flora in NSCLC patients are related to anti-PD-1/PD-L1 therapy.The higher the diversity of intestinal flora,the more sensitive the anti-PD-1/PD-L1 therapy.
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Objective To screen for ferroptosis-related differentially expressed genes(DEGs)of epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)resistance in non-small cell lung cancer(NSCLC).Methods The gene sequencing dataset GSE117846 of NSCLC EGFR-TKIs resistant cells was se-lected from the Gene Expression Omnibus data base(GEO)and screened for DEGs with P＜0.05 and | log2 FC |1.Ferroptosis-related genes were collected using the FerrDb database and jvenn was used to intersected the DEGs screened from GSE117846 dataset with the ferroptosis-related genes obtained from FerrDb database.GO function and KEGG pathway enrichment analysis of intersection genes were performed,and protein-pro-tein interaction(PPI)network was drawn.The score of intersection genes was calculated by using Cytohubba plug-in in Cytoscape software,and the top 10 genes were used for Hub genes screening.ULCAN and GEPIA2 databases were used to analyze the expression of Hub genes in NSCLC and its effect on the survival prognosis of patients.Real-time fluorescence quantitative PCR(qPCR)was used to detect the relative expression levels of Hub gene mRNA in NSCLC patients'cancer tissues,adjacent tissues and in vitro cells to verify the results of bioinformatics analysis.Results A total of 60 ferroptosis-related DEGs of EGFR-TKIs resistance in NSCLC were screened out,including 30 up-regulated genes and 30 down-regulated genes.The 60 genes were mainly enriched in P53 signaling pathway,ferroptosis pathway and FoxO signaling pathway.There were 57 nodes and 99 edges in the PPI network,with an average clustering coefficient of 0.377 and PPI enrichment P＜0.01.The Hub gene screened out by Cytohubba plug-in was tumor protein P63(TP63).ULCAN and GE-PIA2 database analysis showed that the expression of TP63 in lung adenocarcinoma tissue was significantly lower than that in normal tissue,while the expression of TP63 in lung squamous cell carcinoma tissue was sig-nificantly higher than that in normal tissue,and the differences were statistically significant(P＜0.05).In pa-tients with lung adenocarcinoma,there was no significant difference in the survival prognosis between TP63 high and low expression groups(P＞0.05),while in patients with lung squamous cell carcinoma,the survival prognosis of TP63 low expression group was better,and the difference was statistically significant(P＜0.05).QPCR showed that TP63 mRNA highly expressed in lung squamous cell carcinoma tissue and lowly expressed in lung adenocarcinoma tissue compared with adjacent tissues(P＜0.05).The expression of TP63 mRNA was down-regulated in gefitinib-resistant PC9/GR cells(P＜0.05),which was consistent with the re-sults of bioinformatics analysis.Conclusion TP63 may be an important gene linking NSCLC EGFR-TKIs re-sistance to ferroptosis.
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Objective:To investigate whether chlorogenic acid can inhibit the proliferation, migration, invasion and promote apoptosis of lung cancer A549 cells by causing mitochondrial dysfunction through PI3K-Akt pathway.Methods:A549 cells were treated with chlorogenic acid at concentrations of 0, 25, 50, 100, 150, and 200 μg/ml for 48 h. CCK-8 assay was used to detect the cell proliferation rate and calculate the half maximal inhibitory concentration (IC 50). A549 cells were divided into three groups: control group, chlorogenic acid group (IC 50) and chlorogenic acid + 740-YP group (IC 50 chlorogenic acid +50 μg/ml 740YP). After 48 h of intervention, the cell migration distance was detected by cell scratch assay. Cell invasion assay was used to detect cell invasion ability. Cell cycle, apoptosis and mitochondrial membrane potential were detected by flow cytometry. The content of malondialdehyde (MDA) in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein expression of p-PI3K, p-Akt and Caspase3. Results:The IC 50 of chlorogenic acid to A549 cells was 57.45 μg/ml. The results of cell scratch assay showed that the 48 h migration distances of the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (424.80±14.43), (289.67±18.93) and (402.22±17.99) μm, respectively. The results of cell invasion assay showed that the numbers of invasive cells after 48 h were 96.00±6.24, 35.33±7.64 and 83.00±2.00, and the results of flow cytometry showed that the 48 h apoptosis rates were (6.15±0.17) %, (54.63±0.72) % and (17.27±0.39) %, respectively, among the three groups with statistically significant differences ( F=105.98, P<0.001; F=90.62, P<0.001; F=8 321.99, P<0.001). Compared with the control group, the cell migration distances and invasive numbers of chlorogenic acid group and chlorogenic acid + 740YP group were decreased (all P<0.05), while the apoptosis rates were significantly increased (both P<0.001). Compared with chlorogenic acid group, the cell migration distance of chlorogenic acid + 740YP group increased ( P<0.001), the number of cell invasion increased ( P<0.001), and the apoptosis rate decreased ( P<0.001). The results of flow cytometry showed that the proportions of cells in G 0/G 1 phase in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (65.75±0.58) %, (55.84±0.78) % and (55.24±1.37) %, respectively. The proportions of G 2/M phase were (11.21±1.03) %, (20.23±0.62) % and (9.96±0.33) %, and the proportions of S phase were (23.04±0.49) %, (23.92±1.36) % and (34.80±1.15) %, respectively, with statistically significant differences ( F=111.02, P<0.001; F=181.26, P<0.001; F=113.05, P<0.001). Compared with the control group, the proportions of G 0/G 1 phase cells in chlorogenic acid group and chlorogenic acid + 740YP group decreased (both P<0.001), and the proportion of G 2/M phase in chlorogenic acid group increased ( P<0.001), and the proportion of S phase cells in chlorogenic acid + 740YP group increased ( P<0.001). Compared with chlorogenic acid group, the proportion of G 2/M phase cells decreased and the proportion of S phase cells increased in chlorogenic acid + 740YP group (both P<0.001). The results of mitochondrial membrane potential detection showed that the JC-1 fluorescence intensity of mitochondria in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were 39.51±1.32, 10.05±0.19 and 21.85±1.45, respectively, with a statistically significant difference ( F=508.82, P<0.001). Compared with the control group, the fluorescence intensity of chlorogenic acid group and chlorogenic acid + 740YP group decreased (both P<0.001). Compared with chlorogenic acid group, the fluorescence intensity of chlorogenic acid + 740YP group increased ( P<0.001). ELISA results showed that the MDA contents of the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (0.47±0.01), (0.61±0.01) and (0.56±0.01) nmol/ml, respectively, with a statistically significant difference ( F=162.30, P<0.001). Compared with the control group, MDA contents in chlorogenic acid group and chlorogenic acid + 740YP group increased (both P<0.001). Compared with chlorogenic acid group, MDA content in chlorogenic acid + 740YP group decreased ( P=0.001). Western blotting results showed that the relative protein expression levels of p-PI3K in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were 1.01±0.33, 0.28±0.14 and 0.34±0.20, respectively. The relative protein expression levels of p-Akt were 1.00±0.16, 0.43±0.05 and 0.95±0.14, and the relative protein expression levels of Caspase3 were 1.00±0.04, 1.41±0.05 and 0.70±0.13, respectively, and there were statistically significant differences ( F=8.48, P=0.018; F=19.11, P=0.002; F=57.50, P<0.001). Compared with the control group, the expressions of p-PI3K and p-Akt protein in chlorogenic acid group decreased, and the expression of Caspase3 protein increased (all P<0.05). The expressions of p-PI3K and Caspase3 protein in chlorogenic acid + 740YP group decreased (both P<0.05). Compared with chlorogenic acid group, the expression of p-Akt protein in chlorogenic acid + 740YP group increased, and the expression of Caspase3 protein decreased (both P<0.05) . Conclusion:Chlorogenic acid may inhibit the PI3K-Akt pathway by reducing the phosphorylation of PI3K and Akt proteins, resulting in the damage of mitochondrial function and the accumulation of MDA, which eventually leads to the damage of lung cancer A549 cells function and the reduction of cells activity, and then promotes cells apoptosis.
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Objective:To investigate the serum levels of miR-19b and miR-744-5p in patients with non-small cell lung cancer (NSCLC), and to analyze the clinical value of miR-19b and miR-744-5p in the diagnosis of NSCLC.Methods:A total of 226 NSCLC patients (NSCLC group) and 100 healthy people (control group) admitted to Jilin Cancer Hospital from August 2019 to August 2022 were selected as research objects. Quantitative real-time PCR was used to measure and compare the serum levels of miR-19b and miR-744-5p between the NSCLC group and the control group, and the relationships between the two indicators and different clinical and pathological characteristics of NSCLC patients were analyzed. The receiver operating characteristic curve was used to analyze the clinical value of miR-19b, miR-744-5p and their joint detection in the diagnosis of NSCLC.Results:Compared with the control group, the serum miR-19b level (3.86±1.25 vs. 1.06±0.41) in the NSCLC group significantly increased ( t=21.87, P<0.001), while the miR-744-5p level (1.80±0.48 vs. 5.75±1.69) significantly decreased ( t=32.36, P<0.001). The serum miR-19b levels in NSCLC patients with pathological types of adenocarcinoma, maximum tumor diameter ≥3 cm, medium to low differentiation, stage Ⅲ-Ⅳ, and with lymph node metastasis were higher than those in squamous cell carcinoma ( t=5.94, P<0.001), maximum tumor diameter <3 cm ( t=2.65, P=0.009), well differentiation ( t=4.33, P<0.001), stageⅠ-Ⅱ ( t=12.32, P<0.001), patients without lymph node metastasis ( t=8.13, P<0.001), while miR-744-5p levels were lower than those in squamous cell carcinoma ( t=8.27, P<0.001), tumor maximum diameter <3 cm ( t=5.34, P<0.001), well differentiation ( t=6.95, P<0.001), stageⅠ-Ⅱ ( t=11.40, P<0.001), patients without lymph node metastasis ( t=10.36, P<0.001). The area under the curve (AUC) of serum miR-19b combined with miR-744-5p in the diagnosis of NSCLC was 0.914 (95% CI: 0.841-0.959), with sensitivity and specificity of 90.9% and 84.0%, respectively. AUC was significantly than that of the single indicator detection of miR-19b (AUC=0.824, 95% CI: 0.770-0.869) and miR-744-5p (AUC=0.783, 95% CI: 0.709-0.838) ( Z=2.28, P=0.021; Z=2.36, P=0.017) . Conclusion:Serum miR-19b level of NSCLC patients is increased, miR-744-5p levels is decreased, and joint detection of serum miR-19b and miR-744-5p has high clinical value in the diagnosis of NSCLC.
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Objective:To explore the impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer (NSCLC) .Methods:The retrospective analysis of clinical data from 121 patients diagnosed with advanced NSCLC who were admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2021 to January 2023 was conducted. These patients were divided into a control group ( n=57) and an observation group ( n=64) based on the designated treatment protocol. Specifically, individuals in the control group received standard chemotherapy (cisplatin+paclitaxel), while those in the observation group underwent penpilimab therapy in conjunction with conventional chemotherapy. The comparative assessment encompassed short-term clinical efficacy, quality of life, immune function parameters, angiogenic factors [including endostatin, insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) ], circulating endothelial cells, and adverse reactions within the two groups. Results:After 6 courses of treatment, the objective response rate [67.19% (43/64) vs. 49.12% (28/57) ] and disease control rate [87.50% (56/64) vs. 70.18% (40/57) ] in observation group were higher than those in control group, with statistically significant differences ( χ2=4.06, P=0.044; χ2=5.52, P=0.019). The quality of life score of observation group [ (56.77±6.81) points] was significantly higher than that of control group [ (47.73±8.23) points], with a statistically significant difference ( t=6.61, P<0.001) ; The T cell subgroup CD3 + levels [ (63.59±9.00) % vs. (53.06±8.80%), t=6.49, P<0.001], CD4 + levels [ (46.54±8.20) % vs. (30.74±7.32) %, t=11.13, P<0.001] and CD4 +/CD8 + ratio (1.90±0.36 vs. 1.21±0.28, t=11.66, P<0.001) in observation group were significantly higher than those in control group, with statistically significant differences; Endostatin in observation group [ (48.99±3.43) μmol/L] was significantly higher than that in control group [ (31.35±3.87) μmol/L], with a statistically significant difference ( t=26.58, P<0.001), IGF-1 [ (102.31±20.35) μg/L vs. (134.98±19.02) μg/L] and VEGF [ (31.70±4.32) pg/ml vs. (58.71±5.99) pg/ml] were significantly lower in observation group than those in control group, with statistically significant differences ( t=18.73, P<0.001; t=28.14, P<0.001). The number of circulating endothelial cells in observation group [ (58.77±10.03) /ml] was significantly lower than that in control group [ (87.01±8.01) /ml], with a statistically significant difference ( t=17.20, P<0.001). During treatment, there were no statistically significant differences in the incidence of gastrointestinal reaction ( χ2=0.01, P=0.908), leukopenia ( χ2=0.64, P=0.424), thrombocytopenia ( χ2=0.28, P=0.597), anemia ( χ2=1.66, P=0.197), nephrotoxicity ( χ2=0.64, P=0.424), skin rash ( χ2=1.33, P=0.249) between the two groups. Conclusion:The combination therapy of pembrolizumab and chemotherapy for the treatment of advanced NSCLC has demonstrated noteworthy effectiveness. This regimen has the potential to enhance patients' immune functionality, ameliorate their overall quality of life, suppress angiogenesis, and exhibits a commendable profile of safety and reliability.