Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Analysis and Review of Downregulated Actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy

BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Research progress on dynamic monitoring of ctDNA and drug resistance related concomitant mutations in non-small cell lung cancer

Owing to significantly prolonged survival,targeted therapy has become standardized recommendation for advanced non-small cell lung cancer patients with mutated driver genes.However,the genetic status of lung cancer patients is dynamic.By dynamically monitoring the evolution of genes status,differential genes and concomitant genes related to progressive disease could be confirmed early,so as to achieve a more accurate and comprehensive insight of the whole process management of targeted therapy for lung cancer patients.Under the guidance of accurate genetic testing results,it is helpful to provide patients with more effective,long-term,and stable individualized targeted therapy.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

Correlation between pre-anesthesia anxiety and emergence agitation in non-small cell lung cancer surgery patients

BACKGROUND Preoperative anxiety is a common emotional problem during the perioperative period and may adversely affect postoperative recovery.Emergence agitation(EA)is a common complication of general anesthesia that may increase patient discomfort and hospital stay and may be associated with the development of postoperative complications.Pre-anesthetic anxiety may be associated with the development of EA,but studies in this area are lacking.AIM To determine the relationship between pre-anesthetic anxiety and EA after radical surgery in patients with non-small cell lung cancer(NSCLC).METHODS Eighty patients with NSCLC undergoing surgical treatment between June 2020 and June 2023 were conveniently sampled.We used the Hospital Anxiety and Depression Scale’s(HADS)anxiety subscale(HADS-A)to determine patients’anxiety at four time points(T1-T4):Patients’preoperative visit,waiting period in the surgical waiting room,after entering the operating room,and before anesthesia induction,respectively.The Riker Sedation-Agitation Scale(RSAS)examined EA after surgery.Scatter plots of HADS-A and RSAS scores assessed the correlation between patients’pre-anesthesia anxiety status and EA.We performed a partial correlation analysis of HADS-A scores with RSAS scores.RESULTS NSCLC patients’HADS-A scores gradually increased at the four time points:7.33±2.03 at T1,7.99±2.22 at T2,8.05±2.81 at T3,and 8.36±4.17 at T4.The patients’postoperative RSAS score was 4.49±1.18,and 27 patients scored≥5,indicating that 33.75%patients had EA.HADS-A scores at T3 and T4 were significantly higher in patients with EA(9.67±3.02 vs 7.23±2.31,12.56±4.10 vs 6.23±2.05,P<0.001).Scatter plots showed the highest correlation between HADS-A and RSAS scores at T3 and T4.Partial correlation analysis showed a strong positive correlation between HADS-A and RSAS scores at T3 and T4(r=0.296,0.314,P<0.01).CONCLUSION Agitation during anesthesia recovery in patients undergoing radical resection for NSCLC correlated with anxiety at the time of entering the operating room and before anesthesia induction.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report

BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.

Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Clinical Effect of Tislelizumab Combined with Chemotherapy in the Treatment of Stage IIIb-IV Non-Small Cell Lung Cancer

Objective:To analyze the therapeutic effect of tislelizumab combined with chemotherapy in patients with stage IIIb-IV non-small cell lung cancer(NSCLC).Methods:A total of 50 patients with stage IIIb-IV NSCLC admitted between January 2022 and January 2024 were randomly divided into two groups using a random number table.The observation group included 25 cases treated with tislelizumab combined with chemotherapy,while the reference group included 25 cases treated with conventional chemotherapy.The clinical control rate,adverse reaction rate,tumor markers,immune function indicators,and quality of life scores were compared between the two groups.Results:The observation group had a higher clinical control rate and a lower adverse reaction rate compared to the reference group(P<0.05).Before treatment,there were no significant differences in tumor markers,immune function indicators,and quality of life scores between the two groups(P>0.05).Three months after treatment,the tumor marker levels in the observation group were lower than those in the reference group.Except for CD8^(+),all immune function indicators in the observation group were higher than those in the reference group,and the quality-of-life scores in the observation group were higher than those in the reference group(P<0.05).Conclusion:Implementing tislelizumab combined with chemotherapy in patients with stage IIIb-IV NSCLC can improve the clinical control rate,reduce the adverse reaction rate,lower tumor marker levels,protect immune function,and improve quality of life.

Exploring the impact of non-small cell lung cancer tumor microbiome on the efficacy of chemotherapy and immune checkpoint inhibitors

Background:This study aimed to investigate the potential of intratumoral microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers as predictive biomarkers for antitumor efficacy in patients with non-small cell lung cancer.Methods:This study observed patients with metastatic non-driver mutation non-small cell lung cancer who were initially diagnosed at the First Affiliated Hospital of Dalian Medical University’s Department of Oncology from August 2021 to July 2022 and completed at least four cycles of chemotherapy combined with immune checkpoint inhibitor treatment.Lung biopsy tissues,fecal,and peripheral blood samples were collected from these patients.Based on the efficacy of the combined chemotherapy and immunotherapy,patients were divided into an effective group and an ineffective group.The tumor microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers were compared between the two groups.The lung and fecal microbiota were analyzed using 16S rRNA high-throughput sequencing.Flow cytometry was used to detect T-cell subsets,and enzyme-linked immunosorbent assay was employed to measure inflammatory factors.Results:A total of 21 patients were observed.There were significant differences in the tumor microbiota between the responsive and non-responsive groups,particularly the proportion of the genera Sphingomonas and Pseudomonas.The gut microbiome composition changed after treatment,but there were no differences between the two groups before treatment.There were no significant differences in T-cell subsets and inflammatory markers between the responsive and non-responsive groups.Conclusion:The composition of intratumoral microbiota in non-small cell lung cancer patients may serve as an indicator of response to chemotherapy combined with immunotherapy.The predictive value of gut microbiota,T-cell subsets,and inflammatory markers appears limited.Future research should further validate the predictive role of changes in gut microbiota on treatment outcomes.

EGFR-TKI单药与传统化疗方案治疗进展期NSCLC安全性的网状meta分析

目的对一至三代表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)与传统化疗方案治疗进展期非小细胞肺癌(NSCLC)的安全性进行比较,同时采用网状meta分析方法评价三代EGFR-TKI与一、二代之间的安全性。方法检索PubMed、Embase、Cochrane图书馆、中国生物医学文献数据库、中国知网、万方数字化期刊全文数据库、维普数据库,检索时限均为从建库至2020年12月,搜集EGFR-TKI单药对比铂类为基础培美曲塞化疗方案的随机对照试验(RCT)。筛选文献、提取资料,并用Cochrane系统评价偏倚风险评估工具对纳入研究的RCT进行偏倚风险评估,采用RevMan 5.3软件、STATA 15.1软件进行meta分析。结果meta分析结果显示,试验组(EGFR-TKI单药)、对照组(培美曲塞联合铂类)患者的腹泻[相对危险度(RR)=2.16,95%置信区间(CI)0.742~6.297,P>0.05]、便秘(RR=0.44,95%CI 0.187~1.039,P>0.05)发生率比较差异均无统计学意义。试验组白细胞减少发生率、中性粒细胞减少发生率、贫血发生率、血小板减少发生率、食欲不振发生率、恶心发生率均低于对照组(RR=0.21,95%CI 0.10~0.41,P<0.001;RR=0.21,95%CI 0.08~0.55,P<0.001;RR=0.26,95%CI 0.13~0.51,P<0.001;RR=0.39,95%CI 0.24~0.64,P<0.001;RR=0.39,95%CI 0.28~0.55,P<0.001;RR=0.30,95%CI 0.24~0.37,P<0.001);试验组皮疹发生率高于对照组(RR=9.63,95%CI 6.30~14.72,P<0.001)。对一至三代EGFR-TKI的不良反应进行网状meta分析结果显示,三代EGFR-TKI奥希替尼组白细胞减少发生率要高于一、二代EGFR-TKI,贫血发生率与埃克替尼组相似,但高于吉非替尼组和阿法替尼组(均P<0.05)。结论一至三代EGFR-TKI的血液系统、消化系统不良反应发生率均低于传统化疗方案;三代EGFR-TKI与一、二代相比,在白细胞减少及贫血发生率方面各具优势。

基于UHPLC-MS技术的NSCLC血浆生物学标志物的筛选及鉴定研究

目的研究UHPLC-MS技术的NSCLC血浆生物学标志物的筛选及鉴定。方法本研究纳入符合非小细胞肺癌临床诊断标准的60例NSCLC患者,随机分为两组,接受靶向治疗(TACE)的非小细胞肺癌患者为鉴别诊断组,未接受靶向治疗的NSCLC患者为正常对照组。结果在60例NSCLC患者中,通过LC-MS/MS技术共检测到552个生物标志物。在其中17个生物标志物中,有8个出现在已知的EGFR突变患者中,另7个出现在ALK融合患者中,6个出现在HER2突变患者中。此外,NSCLC患者血浆中含有丰富的非编码RNA(miRNA),包括58个miRNA和23个mRNA。结论本研究中,采用LC-MS/MS技术对NSCLC患者血浆进行分析,可快速、高效地获得血浆样品中的生物学标志物。这些标志物可以作为NSCLC诊断的潜在生物学标志物,并且可以用于预测肿瘤进展和不良预后。

High expression of PD-L1 mainly occurs in non-small cell lung cancer patients with squamous cell carcinoma or poor differentiation

Background:Lung cancer is one of the most lethal cancers worldwide,but studies have shown that the higher the expression of programmed cell death protein 1 ligand 1(PD-L1)in non-small cell lung cancer(NSCLC),the more likely it will benefit from anti-PD-L1 immunotherapy.The purpose of our study was to collect and analyze abundant clinical samples in order to provide evidence for clinicians and patients who might consider anti-PD-L1 immunotherapy while jointly formulating treatment plans.Methods:On the one hand,we obtained cases from The Cancer Genome Atlas(TCGA)database,including 498 lung squamous cell cancer(LUSC)patients and 515 lung adenocarcinoma(LUAD)patients.We studied the lung caner driver gene in LUSC and LUAD.On the other hand,PD-L1 expression was detected in lung cancer tissues of 1,008 NSCLC patients with immunohistochemistry staining(IHC),and we studied the correlation between PD-L1 protein expression and clinicopathological characteristics.Results:PD-L1 expression was higher in LUSC than in LUAD at the mRNA level.In univariate analysis,PD-L1 expression at the protein level was higher in patients who were males,were LUSC,were smokers,had a tumor diameter>3 cm,had poor differentiation,or had stages Ⅲ-Ⅳ disease.In multivariate analysis,PD-L1 expression was higher in patients who were LUSC or in poor differentiation.Conclusion:In term of protein level,PD-L1 expression was higher in NSCLC patients who were LUSC or in poor differentiation.We recommend that PD-L1 IHC detection can be routinely performed in such populations that are likely to benefit most from PD-L1 immunotherapy.

炙甘草汤加减联合PD-1治疗晚期NSCLC(气阴两虚型)的疗效

目的:分析炙甘草汤加减联合程序性死亡受体1(programmed cell death protein-1,PD-1)治疗晚期非小细胞肺癌(nonsmall cell lung cancer,NSCLC)(气阴两虚型)的临床疗效。方法:回顾性分析2020年12月至2022年12月就诊于吉林省肿瘤医院、长春中医药大学附属医院的晚期NSCLC(气阴两虚型)患者72例,随机分为两组各36例,对照组(PD-1单抗)、治疗组(PD-1单抗联合炙甘草汤加减)。主要观察指标为免疫功能(CD3^(+)、CD3^(+)/CD4^(+)、CD3^(+)/CD8^(+))和生存质量评分(KPS),次要观察指标为客观缓解率(objective response rate,ORR)、中医症候积分、血清肿瘤标志物癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白片段(CYFRA211)、免疫相关不良反应(胃肠毒性、肺毒性、肝毒性、甲状腺毒性)发生率。结果:治疗组在调节免疫功能CD3^(+)、CD3^(+)/CD4^(+)、CD3^(+)/CD8^(+),提高患者生存质量在T3时间点、T4时间点、降低肿瘤标志物CEA、CY211、改善中医证候咳嗽、乏力、心悸、腹泻的症状和减少免疫相关性肺炎、腹泻方面,均优于对照组(P<0.05)。两组患者客观缓解率分别为治疗组36.1%,对照组25.0%,无显著性差异(P>0.05)。结论:炙甘草汤加减联合PD-1治疗晚期NSCLC的患者,可以显著增强免疫功能,提高临床疗效,减少免疫相关不良反应且安全性较好。

Effects and translatomics characteristics of a small-molecule inhibitor of METTL3 against non-small cell lung cancer

In non-small cell lung cancer(NSCLC),the heterogeneity promotes drug resistance,and the restricted expression of programmed death-ligand 1(PD-L1)limits the immunotherapy benefits.Based on the mechanisms related to translation regulation and the association with PD-L1 of methyltransferaselike 3(METTL3),the novel small-molecule inhibitor STM2457 is assumed to be useful for the treatment of NSCLC.We evaluated the efficacy of STM2457 in vivo and in vitro and confirmed the effects of its inhibition on disease progression.Next,we explored the effect of STM2457 on METTL3 and revealed its effects on the inhibition of catalytic activity and upregulation of METTL3 protein expression.Importantly,we described the genome-wide characteristics of multiple omics data acquired from RNA sequencing,ribosome profiling,and methylated RNA immunoprecipitation sequencing data under STM2457 treatment or METTL3 knockout.We also constructed a model for the regulation of the translation of METTL3 and PD-L1.Finally,we found PD-L1 upregulation by STM2457 in vivo and in vitro.In conclusion,STM2457 is a potential novel suppressor based on its inhibitory effect on tumor progression and may be able to overcome the heterogeneity based on its impact on the translatome.Furthermore,it can improve the immunotherapy outcomes based on PDL1 upregulation in NSCLC.