Risk Of Non-small Cell Lung Cancer Research Articles

Using a Polygenic Risk Score to Improve the Risk Prediction of Non-Small Cell Lung Cancer in Taiwan.

Low-dose computed tomography (LDCT) can help reducing lung cancer mortality. In Taiwan, the existing screening criteria revolve around smoking habits and family history of lung cancer. The role of genetic variation in non-small cell lung cancer (NSCLC) development is increasingly recognized. In this study, we aimed to investigate the potential benefits of polygenic risk scores (PRSs) in predicting NSCLC and enhancing the effectiveness of screening programs. We conducted a retrospective cohort study that included participants without prior diagnosis of lung cancer and later received LDCT for lung cancer screening. Genetic data for these participants were obtained from the project of Taiwan Precision Medicine Initiative. We adopted the model of genome-wide association study-derived PRS calculation using 19 susceptibility loci associated with the risk of NSCLC as reported by Dai et al. We studied a total of 2,287 participants (1,197 male, 1,090 female). More female participants developed NSCLC during the follow-up period (4.4% v 2.5%, P = .015). The only risk factor of NSCLC diagnosis among male participants was age. Among female participants, independent risk factors of NSCLC diagnosis were age (adjusted hazard ratio [aHR], 1.08 [95% CI, 1.04 to 1.11]), a family history of lung cancer (aHR, 3.21 [95% CI, 1.78 to 5.77]), and PRS fourth quartile (aHR, 2.97 [95% CI, 1.25 to 7.07]). We used the receiver operating characteristics to show an AUC value of 0.741 for the conventional model. With the further incorporation of PRS, the AUC rose to 0.778. The evaluation of PRS for NSCLC prediction holds promise for enhancing the effectiveness of lung cancer screening in Taiwan especially in women. By incorporating genetic information, screening criteria can be tailored to identify individuals at higher risks of NSCLC.

Association between fruit intake and non-small cell lung cancer: a Mendelian randomization study.

Several studies have explored the potential relationship between fruit consumption and non-small cell lung cancer (NSCLC). However, the impact of dried fruit on NSCLC risk remains unclear. Additionally, the presence of confounding variables in these observational investigations could not be avoided. Therefore, the aim of this article was to explore the potential relationship between fruits intake and NSCLC. We extracted fruit intake data from the UK Biobank and utilized a genome-wide association study (GWAS) encompassing 218,792 individuals for NSCLC data. We employed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal associations between fruit intake and the risk of NSCLC. The major method of analysis was the inverse variance weighted (IVW). Furthermore, we conducted sensitivity analyses to corroborate the robustness of our findings. The result of our study showed convincing evidence suggesting that dried fruit intake is effective in reducing the risk of NSCLC. Specifically, the odds ratios (ORs) for NSCLC exhibited a noteworthy reduction at 0.32 [95% confidence interval (CI): 0.15, 0.67; P=0.003] with respect to dried fruit intake. Our study underscores a significant correlation between dried fruit consumption and reduced NSCLC risk. In contrast, the association with fresh fruit intake did not reach statistical significance. To substantiate and validate these findings, further prospective randomized controlled trials (RCTs) are warranted in the future.

Plasma fatty acid levels and risk of non-small cell lung cancer: a large-scale prospective cohort study.

Non-small cell lung cancer (NSCLC) ranks among the most prevalent and lethal malignancies globally. Fatty acids (FAs) play a significant role in diverse physiological and pathological mechanisms, yet their precise involvement in NSCLC remains poorly understood. This study utilized a large-scale prospective cohort of 249,132 participants, observed over an average of 12 years, to investigate the relationship between different FAs and NSCLC risk. Analytical approaches included Cox proportional hazards regression, Kaplan-Meier survival analysis, accelerated failure time (AFT) modeling, and restricted cubic spline (RCS) analysis. During the follow-up period, 1,460 participants were diagnosed with NSCLC. Cox regression analysis demonstrated that elevated levels of docosahexaenoic acid (DHA), linoleic acid (LA), and omega-3 were inversely associated with NSCLC risk. Kaplan-Meier curves, along with AFT models, corroborated that elevated concentrations of DHA and LA significantly delayed NSCLC onset. Additionally, RCS analysis uncovered nuanced dose-response relationships between these FAs and NSCLC. Stratified analyses highlighted variability based on smoking status, gender, and body mass index subgroups. The concentration of specific FAs exhibits a significant association with NSCLC risk. These results offer a foundation for devising dietary FA composition adjustments aimed at reducing NSCLC risk.

Correlation of TNF-α polymorphisms with susceptibility to lung cancer: evidence from a meta-analysis based on 29 studies

ObjectiveThis meta-analysis aims to clarify the association between the TNF-α -308G > A and − 238G > A polymorphisms and lung cancer risk.MethodA comprehensive search was conducted for relevant articles across databases such as PubMed, Google Scholar, Web of Science, EMBASE, and CNKI, up to September 25, 2023. Lung cancer risk was assessed by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). The Z-test was used to determine the significance of combined ORs, with P < 0.05 considered statistically significant. All analyses were performed using Comprehensive Meta-Analysis (CMA) 2.0 software.ResultsThe analysis included 19 case-control studies with 3,838 cases and 5,306 controls for the TNF-α -308G > A polymorphism, along with 10 studies comprising 2,427 cases and 2,357 controls for the − 238G > A polymorphism. The − 308G > A polymorphism showed no significant overall relationships, though in the Asian subgroup, the A allele was significantly reduced compared to G (OR: 0.831, p = 0.028) and the AA genotype showed significant reductions versus GG (OR: 0.571, p = 0.021), with no significant correlation in Caucasians. In non-small cell lung cancer (NSCLC), the A allele was associated with increased risk compared to G (OR: 1.131, p = 0.049). For the − 238G > A polymorphism, the AA genotype significantly increased risk compared to GG (OR: 3.171, p = 0.014), while showing a protective effect in Caucasians (OR: 0.120, p = 0.024) and a heightened risk in Asians (OR: 7.990, p = 0.007). In small cell lung cancer (SCLC), the A allele conferred protective effects, whereas NSCLC showed increased risk for the AA genotype (OR: 11.375, p = 0.002).ConclusionThe − 308G > A polymorphism has no significant overall relationships but suggests a protective role of the A allele in the Asian subgroup. Conversely, the − 238G > A polymorphism presents a complex risk profile, increasing lung cancer likelihood in Asians while protecting Caucasians. Notably, the AA genotype significantly raises risk for NSCLC, indicating its potential as a risk factor.

Recurrence-free survival after curative resection of non-small cell lung cancer between inhalational gas anesthesia and propofol-based total intravenous anesthesia: a multicenter, randomized, clinical trial (GAS TIVA trial): protocol description

BackgroundSurgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment that supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibit tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to the retrospective observational nature of previous studies. Therefore, we will test the hypothesis that the recurrence-free survival (RFS) after curative resection of NSCLC is higher in patients who received TIVA than volatile anesthetics (GAS) in this multicenter randomized trial.MethodsThis double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. Exclusion criteria will be contraindications to study drugs, American Society of Anesthesiologists physical status IV or higher, or preexisting distant metastasis or malignant tumor in other organs. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS groups with a 1:1 ratio. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms. The primary outcome will be RFS. Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years.DiscussionConfirmation of the study hypothesis would demonstrate that a relatively minor and low-cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management.Trial registrationThe study protocol was prospectively registered at the Clinical trials (https://clinicaltrials.gov, NCT06330038, principal investigator: Hyun Joo Ahn; date of first public release: March 25, 2024) before the recruitment of the first participant.

Gene-environment interactions between clonal hematopoiesis of indeterminate potential and air pollution in non-small cell lung cancer among non-smokers.

10514 Background: Small particulate matter air pollution (≤ 2.5µm diameter; PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC) among non-smokers. PM2.5 recruits pro-inflammatory macrophages to the lungs, which facilitate the clonal expansion of mutated epithelial cells and eventual transformation to NSCLC. Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition caused by the acquisition of somatic mutations in hematopoietic stem cells. CHIP and its accompanying pro-inflammatory phenotype have been linked with various age-related diseases, including incident NSCLC; however, the mechanisms underlying this relationship are unknown. In this study, we aimed to explore the interaction between CHIP and exposure to PM2.5 in the development of incident NSCLC. Methods: This study was conducted using data from participants in the UK Biobank (n = 451,095). CHIP status was determined from peripheral blood whole exome sequencing data, and defined as the presence of a somatic driver mutation in the blood at variant allele frequency (VAF) ≥2% (PMID: 36652671). Incident NSCLC was determined from UK cancer registry data, and PM2.5 exposure was determined based on ambient regional measures from 2010. Cox proportional hazard models were used to evaluate associations between CHIP, PM2.5, and NSCLC. Proteomics data was measured using OLINK proteomics in a subset of UK Biobank participants (n = 44,625). Results: CHIP was prevalent in 3.4% of UK Biobank participants (n = 15,633; never smokers: 3.0%, n = 6,916/227,133). There were 1983 incident cases of NSCLC (never smokers: n = 307). CHIP status was associated with incident NSCLC when adjusting for smoking status (HR = 1.73, 95% CI: 1.48–2.02) and analyzing exclusively non-smokers (HR = 2.01, 95% CI: 1.34-3.00). PM2.5 levels were not associated with NSCLC in non-smokers (HR = 1.00, 95% CI: 0.89–1.12 per µg/m3 increase in PM2.5); however, there was a significant interaction between PM2.5 and CHIP (HR = 1.46, 95% CI: 1.02–2.11, pint = 0.04), suggesting that it is the interplay between the two that drives incident NSCLC risk. We found no association between PM2.5 levels and increased CHIP prevalence or CHIP VAF. PM2.5 and CHIP were also found to interact to increase systemic inflammatory markers C-reactive peptide (pint = 0.01) and IL-6 (pint = 0.002). Conclusions: PM2.5 and CHIP act as a novel gene x environment interaction pair that play a key role in NSCLC etiology among non-smokers. Rather than acting in isolation to increase risk of NSCLC, PM2.5 intensifies the relationship between CHIP and NSCLC, presumably by exacerbating systemic inflammation and the hyper-inflammatory lung microenvironment. With PM2.5 levels in the UK among the lowest in the world, we posit that the CHIP x PM2.5 interaction contributes substantially to the global burden of NSCLC in non-smokers.

Adherence to the low-fat diet pattern reduces the risk of lung cancer in American adults aged 55 years and above: a prospective cohort study

ObjectivesThere is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DesignA prospective cohort study with a mean follow-up time of 8.8 years. Setting and participantsThis study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. MethodsDietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. ResultsDuring a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66−0.89), NSCLC (HR, 0.79; 95% CI, 0.67−0.93), and SCLC (HR, 0.59; 95% CI, 0.38−0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60−0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10–1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20–3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. ConclusionsOur findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.

Associations of PD-1 and PD-L1 gene polymorphisms with cancer risk: a meta-analysis based on 50 studies.

Programmed death-1 and its ligand-1 (PD-1/PD-L1), immune checkpoints proteins, play a crucial role in anti-tumor responses. A large number of studies have evaluated the relationships of PD-1/PD-L1 polymorphisms with risk of cancer, but evidence for the associations remains inconsistent. Therefore, we performed a meta-analysis to examine the associations between PD-1/PD-L1 single nucleotide polymorphisms (SNPs) and cancer predisposition. Results showed that PD-1.3 and PD-L1 rs17718883 were significantly correlated with overall cancer risk. PD-1.5 was prominently linked with cervical cancer (CC), non-small cell lung cancer (NSCLC), TC (thyroid cancer), brain tumor, AML (acute myelocytic leukemia) and UCC (urothelial cell carcinoma) risk, PD-1.9 with breast cancer (BC), AML, esophageal cancer (EC) and ovarian cancer (OC) risk, and PD-1.3 with colorectal cancer (CRC) and BCC (basal cell carcinoma) risk. PD-1.1 polymorphism slightly elevated BC and OC susceptibility, whereas the rs4143815 variant notably decreased the risk of gastric cancer (GC), hepatocellular carcinoma (HCC) and OC, but increased the risk of BC. PD-1.6 was closely linked with AML risk, PD-L1 rs2890658 with NSCLC, HCC and BC risk, rs17718883 with HCC and GC risk, rs10815225 with GC risk, and rs2297136 with NSCLC and HCC risk. Interestingly, the rs7421861, rs10815225, and rs10815225 markedly reduced cancer susceptibility among Asians. The rs7421861 polymrophism decreased cancer risk among Caucasians, rather than the rs10815225 elevated cancer risk. Our results supported that PD-1 and PD-L1 SNPs were dramatically correlated with cancer risk.

Causal role of metabolites in non-small cell lung cancer: Mendelian randomization (MR) study.

On a global scale, lung cancer(LC) is the most commonly occurring form of cancer. Nonetheless, the process of screening and detecting it in its early stages presents significant challenges. Earlier research endeavors have recognized metabolites as potentially reliable biomarkers for LC. However, the majority of these studies have been limited in scope, featuring inconsistencies in terms of the relationships and levels of association observed.Moreover, there has been a lack of consistency in the types of biological samples utilized in previous studies. Therefore, the main objective of our research was to explore the correlation between metabolites and Non-small cell lung cancer (NSCLC).Thorough two-sample Mendelian randomization (TSMR) analysis, we investigated potential cause-and-effect relationships between 1400 metabolites and the risk of NSCLC.The analysis of TSMR revealed a significant causal impact of 61 metabolites on NSCLC.To ensure the reliability and validity of our findings, we perform FDR correction for P-values by Benjaminiand Hochberg(BH) method, Our results indicate that Oleate/vaccenate (18:1) levels and Caffeine to paraxanthine ratio may be causally associated with an increased risk of NSCLC [Oleate/vaccenate(18:1)levels: OR = 1.171,95%CI: 1.085-1.265, FDR = 0.036; Caffeine to paraxanthine ratio: OR = 1.386, 95%CI:1.191-1.612,FDR = 0.032].

Abstract 2206: Obesity and cancer outcomes among patients with lung cancer and cutaneous melanoma treated with immune checkpoint inhibitors and EGFR inhibitors

Abstract Background: Obesity is a causal factor in cancer risk and progression. Immune checkpoint inhibitors (ICI) and EGFR inhibitors (EGFRi) are indicated for the treatment of several cancers, including non-small-cell lung cancer (NSCLC) and cutaneous melanoma (CM). Improved outcomes was observed with ICI in preclinical studies. We aimed to determine the association of obesity with progression-free survival (PFS) or overall survival (OS) among patients with NSCLC and CM treated with ICI or EGFRi. Methods: This was a retrospective study utilizing 2011-2019 SEER-Medicare data of Medicare Parts A and B enrolled patients ≥66 years diagnosed with NSCLC or CM who received ICI or EGFRi (NSCLC only) within 1-year post-diagnosis. Patients were followed from treatment commencement until death, loss to follow-up, or end of study. Descriptive statistics and survival analysis were used to achieve study objectives. Results: Among 2393 NSCLC patients receiving ICI, obese patients (N=281, 11.7%) were younger (73.4±5.2 yrs vs 74.4±5.9 yrs, p&amp;lt;0.01) with higher CCI scores (2 (IQR=1-4) vs 1 (IQR=0-2), p&amp;lt;0.0001) compared to non-obese patients (N=2,311, 89.2%). Time to progression(TTP) was 41% faster among obese patients (392 days (95% CI=330-468) vs 493 days (95% CI=464-525), p&amp;lt;0.01; HR=1.41 (1.13-1.76), p&amp;lt;0.01) with no significant difference in time to death (TTD) (443 days (404-488) vs 491 days (462-524), p=0.35). Among 880 CM patients, those with obesity (N=91, 10.3%)) were significantly younger (74.7±6.1 yrs vs 76.3±7.3 yrs, p=0.02) with higher CCI scores (2 (IQR=0-4) vs 0 (IQR=0-2), p&amp;lt;0.0001). TTP was 343 days (320-400). TTD was 1,409 days (1,107-2,136) with no association between obesity status and PFS or OS. Among 2,524 NSCLC patients receiving EGFRi, obese patients (126, 5.0%) were younger (73.7±6.1 yrs) vs 75.6±6.5 yrs, p&amp;lt;0.01), had higher CCI scores (2 (IQR=1-3) vs 0 (IQR=0-1), p&amp;lt;0.0001), and longer time to treatment (3 mths (IQR=1-7) vs 2 mths (IQR=1-6), p=0.02). A higher proportion were White (76.2% vs 61.3%, p&amp;lt;0.001). Risk of progression was 48% higher among obese patients (664 dys (496-778) vs 1,231 dys (1,127-1,379), p&amp;lt;0.0001; HR=1.48, 95% CI=1.11-1.97, p&amp;lt;0.01) with no significant difference in TTD (559 dys (440-763) vs 673 dys (639-707), p=0.35). Conclusion: Obesity with associated with PFS but not OS among patients with NSCLC with no association observed among patients with CM. Given that the link between obesity and NSCLC risk remains controversial, the observed association with PFS may be linked to the absence of the paradoxical effect of improve outcomes that may be seen with cancers caused by obesity such as CM. Citation Format: Sabina O. Nduaguba, Lori Hazlehurst. Obesity and cancer outcomes among patients with lung cancer and cutaneous melanoma treated with immune checkpoint inhibitors and EGFR inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2206.

Gut Microbiota Signatures with Potential Clinical Usefulness in Colorectal and Non-Small Cell Lung Cancers.

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

Combining Classic and Novel Neutrophil-Related Biomarkers to Identify Non-Small-Cell Lung Cancer

Background: Recent studies have revealed that neutrophils play a crucial role in cancer progression. This study aimed to explore the diagnostic value of neutrophil-related biomarkers for non-small-cell lung cancer (NSCLC). Methods: We initially assessed the associations between classic neutrophil-related biomarkers (neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil counts (NEU), absolute lymphocyte counts (LYM)) and NSCLC in 3942 cases and 6791 controls. Then, we measured 11 novel neutrophil-related biomarkers via Luminex Assays in 132 cases and 66 controls, individually matching on sex and age (±5 years), and evaluated their associations with NSCLC risk. We also developed the predictive models by sequentially adding variables of interest and assessed model improvement. Results: Interleukin-6 (IL-6) (odds ratio (OR) = 10.687, 95% confidence interval (CI): 3.875, 29.473) and Interleukin 1 Receptor Antagonist (IL-1RA) (OR = 8.113, 95% CI: 3.182, 20.689) shows strong associations with NSCLC risk after adjusting for body mass index, smoking status, NLR, and carcinoembryonic antigen. Adding the two identified biomarkers to the predictive model significantly elevated the model performance from an area under the receiver operating characteristic curve of 0.716 to 0.851 with a net reclassification improvement of 97.73%. Conclusions: IL-6 and IL-1RA were recognized as independent risk factors for NSCLC, improving the predictive performance of the model in identifying disease.

Comprehensive functional interrogation of susceptibility loci in GWASs identified KIAA0391 as a novel oncogenic driver via regulating pyroptosis in NSCLC

Approximately 51 non-small-cell lung cancer (NSCLC) risk loci have been identified by genome-wide association studies (GWASs). We conducted a high throughput RNA-interference (RNAi) screening to identify the candidate causal genes in NSCLC risk loci. KIAA0391 at 14q13.1 had the highest score and could promote proliferation and metastasis of NSCLC in vitro and in vivo. We next prioritized rs3783313 as a causal variant at 14q13.1, by integrating a large-scale population study consisting of 27,120 lung cancer cases and 27,355 controls, functional annotation, and expression quantitative trait locus (eQTL) analysis. Then we found that rs3783313 could facilitate a promoter-enhancer interaction to upregulate KIAA0391 expression by affecting the affinity of transcription factor NFYA. Mechanistically, KIAA0391 knockdown dramatically influenced pyroptosis-related pathways and increased the expression of CASP1. And KIAA0391 transcriptionally repressed CASP1 by binding to SMAD2 and induced an anti-pyroptosis phenotype, promoting tumorigenesis of NSCLC, which provides new insights and potential target for NSCLC.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer

BackgroundSarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients.MethodsThis study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC.ResultsThe ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC.ConclusionRDW is associated with sarcopenia risk in early-stage NSCLC.

AuNPs/CNC Nanocomposite with A "Dual Dispersion" Effect for LDI-TOF MS Analysis of Intact Proteins in NSCLC Serum Exosomes.

Detecting exosomal markers using laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) is a novel approach for examining liquid biopsies of non-small cell lung cancer (NSCLC) samples. However, LDI-TOF MS is limited by low sensitivity and poor reproducibility when analyzing intact proteins directly. In this report, gold nanoparticles/cellulose nanocrystals (AuNPs/CNC) is introduced as the matrix for direct analysis of intact proteins in NSCLC serum exosomes. AuNPs/CNC with "dual dispersion" effects dispersed and stabilized AuNPs and improved ion inhibition effects caused by protein aggregation. These features increased the signal-to-noise ratio of [M+H]+ peaks by two orders of magnitude and lowered the detection limit of intact proteins to 0.01mgmL-1. The coefficient of variation with or without AuNPs/CNC is measured as 10.2% and 32.5%, respectively. The excellent reproducibility yielded a linear relationship (y=15.41x - 7.983, R2=0.989) over the protein concentration range of 0.01 to 20mgmL-1. Finally, AuNPs/CNC-assisted LDI-TOF MS provides clinically relevant fingerprint information of exosomal proteins in NSCLC serum, and characteristic proteins S100 calcium-binding protein A10, Urokinase plasminogen activator surface receptor, Plasma protease C1 inhibitor, Tyrosine-protein kinase Fgr and Mannose-binding lectin associated serine protease 2 represented excellent predictive biomarkers of NSCLC risk.

The Role of Human Papilloma Virus (HPV) in Primary Lung Cancer Development: State of the Art and Future Perspectives.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Notably, the incidence of lung cancer among never-smokers, predominantly women, has been rising in recent years. Among the various implicated risk factors, human papilloma virus (HPV) may play a role in the development of NSCLC in a certain subset of patients. The prevalence of high-risk HPV-DNA within human neoplastic lung cells varies across the world; however, the carcinogenetic role of HPV in NSCLC has not been completely understood. Bloodstream could be one of the routes of transmission from infected sites to the lungs, along with oral (through unprotected oral sex) and airborne transmission. Previous studies reported an elevated risk of NSCLC in patients with prior HPV-related tumors, such as cervical, laryngeal, or oropharyngeal cancer, with better prognosis for HPV-positive lung cancers compared to negative forms. On the other hand, 16% of NSCLC patients present circulating HPV-DNA in peripheral blood along with miRNAs expression. Typically, these patients have a poorly differentiated NSCLC, often diagnosed at an advanced stage. However, HPV-positive lung cancers seem to have a better response to target therapies (EGFR) and immune checkpoint inhibitors and show an increased sensitivity to platinum-based treatments. This review summarizes the current evidence regarding the role of HPV in NSCLC development, especially among patients with a history of HPV-related cancers. It also examines the diagnostic and prognostic significance of HPV, investigating new future perspectives to enhance cancer screening, diagnostic protocols, and the development of more targeted therapies tailored to specific cohorts of NSCLC patients with confirmed HPV infection.

Particle filter-based parameter estimation algorithm for prognostic risk assessment of progression in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a malignant tumor that threatens human life and health. The development of a new NSCLC risk assessment model based on electronic medical records has great potential for reducing the risk of cancer recurrence. In this process, machine learning is a powerful method for automatically extracting risk factors and indicating impact weights for NSCLC deaths. However, when the number of samples reaches a certain value, it is difficult for machine learning to improve the prediction accuracy, and it is also challenging to use the characteristic data of subsequent patients effectively. Therefore, this study aimed to build a postoperative survival risk assessment model for patients with NSCLC that updates the model parameters and improves model accuracy based on new patient data. The model perspective was a combination of particle filtering and parameter estimation. To demonstrate the feasibility and further evaluate the performance of our approach, we performed an empirical analysis experiment. The study showed that our method achieved an overall accuracy of 92% and a recall of 71% for deceased patients. Compared with traditional machine learning models, the accuracy of the model estimated by particle filter parameters has been improved by 2%, and the recall rate for dead patients has been improved by 11%. Additionally, this study outcome shows that this method can better utilize subsequent patients’ characteristic data, be more relevant to different patients, and help achieve precision medicine.

Impact of IL-6 and IL-1β Gene Variants on Non-small-cell Lung Cancer Risk in Egyptian Patients

Lung cancer is a serious health and life issue, with the fastest-growing incidence and fatality rates worldwide. It is now clear that inflammation is a key factor involved in all aspects of carcinogenesis, notably lung cancer development. Genetic changes, including polymorphisms in inflammatory genes, are supposed to be a significant cause of increased lung cancer risk. The main idea of this research was to disclose the linkage between both IL-6 rs1800795 and IL-1β rs16944 variants and susceptibility to non-small-cell lung cancer (NSCLC) in Egyptians. This case–control design was composed of 127 cases and 138 controls, which were genotyped using the ARMS-PCR technique. To examine the NSCLC susceptibility under various genetic models, the odds ratio (OR) and 95% confidence intervals (CIs) were determined by logistic regression. Rs1800795 of the IL-6 gene was linked to higher odds of NSCLC under the allele model (adjusted, OR 2.28; 95% CI 1.2–4.33; p = 0.011). In the genetic models, IL-6 rs1800795 elevated the odds of NSCLC, while IL-1β rs16944 decreased the odds of NSCLC. Stratification analysis showed that IL-6 rs1800795 greatly increased the NSCLC risk in females and adenocarcinoma subtypes, whereas IL-1β rs16944 largely decreased the NSCLC risk for males, patients aged < 55, and nonsmokers. Regarding clinical data, the IL-6 variant was remarkably correlated with tumor size. This work primarily established that IL-6 and IL-1β variants have a great impact on NSCLC development in the Egyptian population; thus, it may be a supportive guide for earlier NSCLC prevention.

Identification of genetically predicted DNA methylation markers associated with non-small cell lung cancer risk among 34,964 cases and 448,579 controls.

Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated. The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways. Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p≤1.67×10-6 ) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p≤1.28×10-3 ), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified. Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby. The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non-small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.

CCR5 promoter polymorphisms associated with nonsmall cell lung cancer.

C-C chemokine receptor 5 (CCR5) plays a crucial role in the regulation of immune cell activation and migration as well as the progression of many cancers. We performed an in silico analysis using public data resources and found that the lung cancer patients with higher CCR5 expression had a notably better overall survival than those with lower CCR5 expression patients and CCR5 expression level is positive correlated with the infiltration of immune cells, such as B, CD8+ T and CD4+ T cells, in both lung adenocarcinoma and lung squamous cell cancer. In the present study, we investigated the association between the promoter polymorphism of CCR5 and nonsmall cell lung cancer (NSCLC). A case-control study of 449 NSCLC patients and 516 controls of Chinese Han population was conducted, along with polymorphism detection using a sequencing method. A dual-luciferase reporter assay system was used to analyse the transcriptional activity of CCR5 promoter variations. Our results showed that the frequency of rs1799987-AA was significantly higher in the NSCLC group than in the controls in recessive model (p=.007, OR=1.66 95% confidence interval [CI]: 1.14-2.40, adjusted by sex and age); the G allele showed a significant associated with NSCLC in dominant model (p=.003, OR=1.64, 95%CI: 1.18-2.28, adjusted by sex and age). Compared with haplotype H1 rs2227010-rs2734648-rs1799987-rs1799988-rs1800023-rs1800024: A-T-G-T-G-C, haplotype H5: A-G-G-T-G-C increased the risk of NSCLC by over 10-fold (p<.0001, OR=16.09, 95%CI: 5.37-48.20, adjusted by sex and age) and notably depressed the transcriptional activity of the CCR5 promoter in 293T, A549, H1299 and HeLa cells. In conclusion, CCR5 promoter polymorphisms are significantly associated with NSCLC by affecting the transcriptional activity of the CCR5 promoter.