Glabridin and Anti-Non-Muscle Myosin IIA Therapy Disrupts Non-Small Cell Lung Carcinoma Motility

Lung cancer is the leading cause of cancer related death in the United States killing over 130,000 people each year. While a combination of chemo and radiation therapy may be effective, surgery is still required for many patients. Without surgery, the disease may progress and lead to metastases. We sought to determine if treatment with anti-non-muscle myosin IIA antibody would inhibit movement of the cells in the presence and absence of glabridin (an isoflavonoid compound shown to inhibit cell migration by inhibiting myosin). We compared inhibition by glabridin to that of an anti-non-muscle myosin IIA antibody and a combination therapy of both at 12 and 24 hours post wound creation. Cells that took up the anti-non-muscle myosin IIA antibody were greatly inhibited in motility and exhibited no significant change in wound healing. Glabridin treatment resulted in a dramatic increase in wound size within 12 hours and regeneration within 24 hours. The greatest decrease in motility was observed in cells treated with the combination of both glabridin and anti-non-muscle myosin IIA antibody. By 24 hrs, cell migration had halted due to death of the cells resulting from this combination. Further testing needs to be done to determine a safe mode of delivery of the combination therapy to ensure only local distribution. Controlled release drug delivery depot systems have been used as a means to provide local release of drugs intra-tumorally or adjacent to the cancerous tissue after surgical resection and have great potential.

Aquaporin 5 Expression and Its Relationship to Apoptosis in Different Grades of Differentiated Non-Small Cell Lung Carcinoma

Aquaporin 5 has been recently found as an important oncogenic marker whose expression levels seem to be determined by the level of cellular differentiation. Despite aquaporin volume decrease (AVD) being the most conserved earliest event in apoptosis, there is still a paucity of studies exploring on aquaporin expression and its relationship with apoptosis in cancer. The aim of this study was to investigate the expression of aquaporin 5 channel protein and to explore on its relationship with apoptosis in well and poorly differentiated non-small cell lung carcinoma both in-vivo and in-vitro. Findings from the study showed that the expression of AQP5 both in-vivo and in-vitro was dependent on the type and degree of tumour differentiation. In-vivo, an increase in aquaporin 5 expression was associated with an increased apoptosis in both poorly and highly differentiated adenocarcinoma (AC) while there was no association between aquaporin 5 expression and apoptosis in both poorly and highly differentiated squamous cell carcinoma (SCC). In vitro, differentiation therapy in the form of ATRA decreased both cell proliferation and increased the expression of AQP5 in A549 cells. The cytomorphological changes, expression of differentiation markers and flow cytometry apoptotic results were dependent on the dose of ATRA treatment. In conclusion, a higher expression of aquaporin 5 was found to promote the rate of the apoptotic process in lung adenocarcinoma (AC).

AN IMMUNOHISTOCHEMICAL STUDY OF OCCULT MICRO- METASTASES IN REGIONAL LYMPH NODES OF 94 PATIENTS WITH STAGE I NON-SMALL CELL LUNG CARCINOMA

In the study, 739 regional lymph nodes from 94 patients with stage I non- small cell lung carcinoma (NSCLC) were studied by immunohistochemical techniques. These lymph nodes contained no metastatic tumor as assessed by conventional histopatholgy were recut. A series of consecutive sections from the original blocks were immunostained with poly-and monoclonal antibodies to cytokeratins, carcinoembryonic antigen (CEA), and human milk fat globulin membrane antigen (HMFG-2). Single tumor cells or small clusters of tumor cells, not visible on routine examination, were readily detected. The actual number of lymph nodes that contained occult tumor cells was 123 (16.6%) from 53 patients (56.4%). The majority of 102 immunostalned positive nodes were distributed in the hllar (29% ) and peribronchlal (25%) regions. Our data indicate that (1) a series of consecutive sections and immunohistochemistry may greatly Increase the diagnostic yield of occult micrometastases in lymph nodes; (2) the high incidence of occult metastases in NSCLC may be of Importance in relation to their rapid dissemination and high death rates; (3) the high frequencyof occult nodal metastases in NSCLC raises questions in regard to our presently used criteria for staging, prognosis and treatment of ostensibly stage I disease; and (4) perhaps dissections of hllar and peribronchlal nodes will have an Importantly clinical significance in prevention of wide dissemination of tumor cells.

Effect of miR-375 on non-small cell lung carcinoma invasion,migration,and proliferation through the CIP2A pathway

Lung cancer is one of the malignant tumors with the fastest increase in morbidity and mortality and the greatest threat to people’s health and life.Worldwide,lung cancer is the leading cause of cancer death in men and the second leading cause of cancer deaths in women[1].Lung cancer is divided into two major groups,small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC)[2].SCLC accounts for approximately 20%of lung cancers.It has a high degree of malignancy and early metastasis,and is sensitive to chemotherapy and radiotherapy.The initial remission rate is high,but it is prone to secondary drug resistance and relapse.Chemotherapy is the mainstay.NSCLC includes three major histological subtypes,lung squamous cell carcinoma(SCC),lung adenocarcinoma(ADC),and large cell lung cancer(LCLC),accounting for approximately 80%of lung cancers.Cell division is slower,and the diffusion shift is relatively late[3].Nevertheless,while current research on the biological characteristics of different histological subtypes of NSCLC is expanding,its basic molecular mechanism is not yet clear.For example,smoking is more risky for SCC than ADC[4].Micro-RNA is an endogenous small RNA with a length of approximately 19–25 nucleotides.As a short non-coding RNA,its main function is to regulate the expression level of mRNA.miRNAs can be used as proto-oncogenes or tumor suppressors,and participate in various processes including proliferation,apoptosis,metabolism,and differentiation of cells through targeted binding to different transcripts[5].miRNAs are expressed in specific tissue and developmental stages under normal physiological conditions,but abnormal expression of miRNAs can lead to a series of pathological states,such as tumorigenesis and metastasis[6–7].miRNA regulates the function of tumor cells by regulating the expression of functional proteins.For example,miR-206 promotes breast cancer proliferation by inhibiting estrogen receptor alpha(ERα)while miR-34a downregulates E2 factor transcription factor 2(E2F2)expression to regulate the cell cycle and apoptosis[8–9].CIP2A,as an oncogenic protein during the malignant transformation and progression of cancer cells,has been shown to have a certain relationship with the efficacy of many drugs in cancer treatment.Oncoprotein CIP2A,also known as KIAA1524 or P90,was named in 2007 and is a cancerous inhibitor of PP2A due to its effect on cancer cells.The stability of PP2A and MYC is controlled to form a"carcinogenic connection"[10].In this study,we found that miR-375 regulated the expression of downstream protein kinase B(AKT),MYC,p-AKT and other related proteins through the CIP2A/PP2A signaling pathway,inhibiting the cancer phenotype of lung cancer,and affecting cell invasion,proliferation,apoptosis,and the cell morphology process.We found that the CIP2A gene is a direct binding target of miR-375.Thus,it has become a topic of great interest to explore whether and how miR-375 regulates ADC cells through the CIP2A signaling pathway.By up-regulating miR-375 in a lentivirus-transfected A549 cell line,we found that a series of phenotypes,including cell invasion,proliferation,and apoptosis were changed,and that CIP2A and its downstream signaling proteins were also changed.

Two Molecular Markers of Early Non-Small Cell Lung Carcinoma Based on Gene Expression in Peripheral Blood

Background: Lung cancer is among the most common cancers. Search is ongoing to find biomarkers to improve the diagnosis lung cancer techniques in early stages. In this study we evaluate the sensitivity and specificity of the MUC1 and CEA gene expressions in the peripheral blood of non-small cell lung cancer (NSCLC). Material and Methods: This study was done in Masih Daneshvari Hospital, Tehran, Iran and was case/control study that conducted on 30 NSCLC patients and 30 healthy controls. Peripheral blood was collected and total RNA was extracted then cDNA was synthesized. Sample was separately assessed by real time PCR. Results: The expression of CEA gen was positive in 24 patients indicating 80% sensitivity for this marker. The expression of CEA gen was positive in 9 controls out of 30 each. A statistically significant difference was detected between patients and healthy controls with regard to CEA mRNA expression (P 0.001). The MUC1 gen expressed in 20 out of 30 patients, while it expressed in 3 controls. The difference in MUC1 mRNA expression was statistically significant between NSCLC patients and healthy controls (P 0.001). Conclusion: MUC1 and CEA are molecular biomarkers with relatively favorable sensitivity for primary diagnosis of NSCLC.

Hypofractionated Radiotherapy for Stage I Non-small Cell Lung Carcinoma in Patients Aged 75 Years and Older

Purpose: We report our single-institution experience using hypofractionated radiotherapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) Non-Small Cell Lung Carcinoma. Materials and methods: This is a single-institution, retrospective analysis examining disease free and overall survival and toxicity after hypofractionated radiation therapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) NSCLC. Between 1991 and 2005, a total of 33 such patients were identified with a median age of 79 years. Patients were treated with a median total dose of 7000 cGy using median daily dose fractions of 250 cGy. Analysis of competing risks (local failure, distal failure or death as the first event) was performed and cumulative incidence functions (CIF) were estimated. Results: The median length of follow-up was 19.8 months (range: 4.3 - 103.8 months). Of the 33 patients treated, 21 (63.6% of total) had no evidence of disease recurrence on follow-up imaging over the course of the study. Of the 12 patients with disease recurrence, 6 (18.2% of total) had local failure as the first event and 6 (18.2% of total) had distant metastasis as the first event. Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 19.5% (95%CI: 7.6%, 35.6%);the probability of distal failure as the first detected event was 21.5% (95%CI: 7.9%,39.4%);and the probability of death without recording a failure was 44.1% (95%CI: 26.1%, 60.7%). There were no treatment related deaths reported. Conclusions: Elderly patients diagnosed with stage I non-small cell lung cancer may safely be offered hypofractionated radiotherapy as an effective option with curative intent.

Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)are highly sensitive for diagnosing and staging lung cancer.In recent years,targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma(NSCLC).Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach.AIM To evaluate the feasibility and accuracy of tissue samples obtained using EUSFNA and EBUS-TBNA for molecular diagnosis of NSCLC.METHODS A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019.All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture.We detected abnormal expression of EGFR,KRAS,MET,HER2,ROS1 and anaplastic lymphoma kinase protein.Two patients failed to complete molecular testing due to insufficient tumor tissue.The clinical features,puncture records,molecular testing results and targeted treatment in the remaining 81 patients were summarized.RESULTS In a total of 99 tissue samples obtained from 83 patients,molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9%(93/99).Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue.In the remaining 81 patients,62 cases(76.5%)were found to have adenocarcinoma,11 cases(13.6%)had squamous cell carcinoma,3 cases(3.7%)had adenosquamous carcinoma and 5 cases(6.2%)had NSCLC-not otherwise specified.The results of molecular testing showed EGFR mutations in 21 cases(25.9%),KRAS mutations in 9 cases(11.1%),ROS-1 rearrangement in 1 case(1.2%)and anaplastic lymphoma kinase-positive in 5 cases(6.2%).Twentyfour patients with positive results received targeted therapy.The total effectiveness rate of targeted therapy was 66.7%(16/24),and the disease control rate was 83.3%(20/24).CONCLUSION Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.

Primary parenchymal squamous cell carcinoma of the kidney:A case report

BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases reported.CASE SUMMARY This study reports a 51-year-old man with primary SCC of the renal parenchyma.The patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross hematuria.SCC antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated calculi.The patient underwent laparoscopic unilateral nephrectomy and lymph node dissection.Postoperative pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and ureter.The pathological stage was Pt3aN1M0.Four months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena cava.The patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease progression.CONCLUSION We report a case of primary SCC of the renal parenchyma,a rare renal malignancy.The clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis challenging.According to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.

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.

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.

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.

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.

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.

Network Structure and Variability of Recurrence Fear in Early-Stage Non-Small Cell Lung Cancer:A Symptom Network Analysis

Background:Lung cancer,one of the most prevalent and deadly malignancies worldwide,not only poses a significant physical burden but also a profound psychological challenge to patients.Among these psychological challenges,the fear of recurrence stands out as a particularly distressing issue.This fear,often rooted in the patients’past experiences with the disease and its treatment,can significantly impact their quality of life,mental health,and even compliance with follow-up care.Moreover,this fear can be exacerbated by the lack of understanding and support from healthcare professionals and family members,further isolating patients and compounding their psychological burden.Therefore,understanding and addressing the fear of recurrence in lung cancer patients is crucial for improving their overall well-being and outcomes.Aims:This study aims to develop a symptom network model for fear of recurrence in early-stage lung cancer patients,analyzing symptom correlations to enhance healthcare providers’understanding and management of these symptoms,thereby improving patient outcomes and quality of life.Design:A cross-sectional study design was used.Method:We employed convenience sampling to recruit 551 lung cancer patients from the Thoracic Surgery Department of a tertiary hospital in Beijing between January 2023 and December 2023.A cross-sectional study was conducted using the General Information Questionnaire,Fear of Disease Progression Scale,and Level of Hope Scale.Network analysis was performed with JASP 0.18.3.0 using the EBICglasso method,and centrality metrics including Betweenness,Closeness,Degree centrality,and Expected influence were calculated.Results:Symptom network analysis identified fear of family impact and future work disruption as central to recurrence fear in these patients.Gender-based analysis revealed‘fear of being unable to continue work’as central in males,while‘fear of affecting family members’was central in females.Among adolescents,concerns about future work,medication side effects,and family impact showed the highest expected influence.In contrast,older patients predominantly feared major treatment implications.One-way ANOVA indicated that older age correlated with reduced recurrence fear,and higher hope levels significantly mitigated this fear.Conclusion:This study broadens understanding of fear of recurrence across demographic variables like gender and age,elucidating symptom interrelations and impacts.Future strategies should focus on patient-specific differences in recurrence fear to formulate targeted interventions.Relevance to Clinical Practice:Through in-depth analysis of the symptom network,healthcare professionals can more comprehensively understand the psychological responses of lung cancer patients when they face the risk of recurrence,and then formulate more precise and personalized treatment plans.At the same time,doctors and nurses can adjust treatment strategies in a timely manner according to the changes in the patient’s symptom network and provide more comprehensive psychological support,thus enhancing the patient’s treatment adherence and outcome.Patient Contribution:People who were invited to participate voluntarily completed a range of questionnaires.

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.

Employing a Backpropagation Neural Network for Predicting Fear of Cancer Recurrence among Non-Small Cell Lung Cancer Patients

Objective:Non-small cell lung cancer(NSCLC)patients often experience significant fear of recurrence.To facilitate precise identification and appropriate management of this fear,this study aimed to compare the efficacy and accuracy of a Backpropagation Neural Network(BPNN)against logistic regression in modeling fear of cancer recurrence prediction.Methods:Data from 596 NSCLC patients,collected between September 2023 and December 2023 at the Cancer Hospital of the Chinese Academy of Medical Sciences,were analyzed.Nine clinically and statistically significant variables,identified via univariate logistic regression,were inputted into both BPNN and logistic regression models developed on a training set(N=427)and validated on an independent set(N=169).Model performances were assessed using Area Under the Receiver Operating Characteristic(ROC)Curve and Decision Curve Analysis(DCA)in both sets.Results:The BPNN model,incorporating nine selected variables,demonstrated superior performance over logistic regression in the training set(AUC=0.842 vs.0.711,p<0.001)and validation set(0.7 vs.0.675,p<0.001).Conclusion:The BPNN model outperforms logistic regression in accurately predicting fear of cancer recurrence in NSCLC patients,offering an advanced approach for fear assessment.

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.