Lung Cancer Patients Research Articles

Defining the optimal setting for transcriptomic analyses on blood samples for response prediction in immunotherapy-treated NSCLC patients

Transcriptomic profiling of blood immune cells offers a promising alternative to invasive, sampling bias-prone tissue-based biomarker assays for predicting immune checkpoint inhibitor (ICI) therapy response in non-small cell lung cancer (NSCLC) patients. However, the optimal analytical approach to identify systemic correlates of response still needs to be explored. We collected peripheral blood mononuclear cells and whole blood (WB) samples from 33 ICI-treated NSCLC patients before ICI treatment and at the first response evaluation. After bulk polyadenylated RNA-sequencing, we assessed differences in gene expression profiles between non-responders and responders using differential expression analysis, single sample gene set enrichment analysis (ssGSEA), and cell type deconvolution. We evaluated gene expression values, ssGSEA scores, and deconvolved cell type proportions to distinguish non-responders from responders via ROC curve (AUC) analysis, training a logistic regression classification model. Gene expression values and deconvolved proportions yielded the best results with WB samples after treatment (AUC = 0.87 and 0.85, respectively). Overall, ssGSEA scores showed superior classification performance across all sample types and timepoints (AUC > 0.7). In conclusion, transcriptomic analysis through ssGSEA demonstrated the best performance as a non-invasive biomarker for predicting clinical benefit in ICI-treated NSCLC patients, with gene expression and deconvolution on post-treatment WB samples also showing promising results.

Impact of CA9 expression in the diagnosis of lymph-node metastases in non-small cell lung cancer based on [18F]FDG PET/CT.

Lung cancer is the leading cause of the global cancer incidence and mortality. It is important to obtain an accurate diagnosis of lymph-node metastasis before surgery to select the therapeutic strategy for non-small cell lung cancer (NSCLC) patients. Carbonic anhydrase 9 (CA9) is considered a marker of hypoxia and it has reported that CA9 is associated with tumor invasion and metastasis. In this study, the correlation between the CA9 expression for lymph-node metastases in NSCLC and [18F]FDG PET/CT results was investigated in order to clarify the efficacy of [18F]FDG PET/CT for detecting lymph-node metastases of NSCLC patients. Among the 564 patients who underwent surgical treatment for NSCLC between 2010 and 2016 at our hospital, a total of 338 patients who underwent preoperative [18F]FDG PET/CT were included in this study. CA9 expression was evaluated by immunochemistry. A lymph node with maximum standardized uptake value (SUVmax) ≥2.5 on [18F]FDG PET/CT was preoperatively defined as a metastatic lymph node. CA9 positivity was detected in 122 patients; the other 216 patients were CA9-negative. The CA9-positive NSCLC cases significantly associated with pleural invasion (p = 0.0063), pT-factor (p = 0.0080), pN-factor (p = 0.036) and pStage (p = 0.043). CA9-positive patients presented significantly poorer survival rate for OS than that of the CA9-negative patients (p = 0.0024). In the multivariable analysis, histological SCC and CA9 positivity were independent poor-prognosis factors for OS. For the total patient population, the sensitivity and specificity of [18F]FDG PET/CT for lymph-node metastases were 54% and 89%, respectively. In contrast, the sensitivity and specificity were particularly low in the CA9-positive SCC cases (36% and 69%, respectively). [18F]FDG PET/CT might not be useful for diagnosing lymph-node metastases of CA9-positive SCC cases of NSCLC.

Dysregulation of SIGLEC1 in non-small cell lung cancer: prognostic implications and immunomodulatory role-a multicenter cohort study

PurposeTo investigate the clinical significance and functional role of SIGLEC1-positive cells in non-small cell lungcancer (NSCLC) patients, focusing on their prognostic impact and therapeutic response.MethodsA multicenter retrospective cohort analysis was conducted, integrating data from multiple sources. Weanalyzed SIGLEC1 expression in NSCLC tissues, clinicopathological features, overall survival outcomes,chemotherapy responsiveness, and sensitivity to targeted therapies. We also developed a prognostic model basedon SIGLEC1 expression and clinical variables.ResultsSIGLEC1 expression was significantly downregulated in NSCLC tissues, and the density of SIGLEC1-positivecells was inversely correlated with various clinicopathological features. Notably, patients with high infiltration ofSIGLEC1-positive cells exhibited significantly better overall survival outcomes. Furthermore, elevated SIGLEC1expression was associated with improved responsiveness to chemotherapy and demonstrated distinct patterns ofsensitivity to targeted therapies. A robust prognostic model was developed by integrating SIGLEC1 expression andclinical variables.ConclusionsThis study highlighted the downregulation of SIGLEC1 in NSCLC tissues and its significant associationwith patient prognosis and therapeutic response. The findings suggested that SIGLEC1 played a critical role inmodulating the tumor immune microenvironment and has potential as both a prognostic biomarker and therapeutictarget in NSCLC.

Characterization of renal injury in non-squamous non-small cell lung cancer patients treated with pemetrexed: A single-center retrospective study.

Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed. We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.

Analysis of the Status Quo and Influencing Factors of Advanced Lung Cancer Patients’ Quality of Life

Objective: To investigate the quality of life and related influencing factors of patients with advanced lung cancer. Methods: A cross-sectional survey was conducted on 51 patients with advanced lung cancer who were hospitalized in the Department of Oncology from January 2023 to December 2023, and the influencing factors of patients’ quality of life were analyzed. Results: Among the five functional scales (physical, role, cognitive, emotional, and social functioning) of the QLQ-C30 scale, the social and emotional function scores were the lowest, respectively 16.7 (IQR: 0, 33.3) points, and 16.7 (IQR: 8.3, 25), and among the three symptom scales (fatigue, pain, nausea and vomiting), the fatigue symptom score was the highest: 77.7 (IQR: 66.7, 88.9) points. The results of Spearman correlation analysis showed that the anxiety score of patients with advanced lung cancer was positively correlated with depression score (P &lt; 0.01), while the quality of life of patients with advanced lung cancer was not correlated with anxiety and depression score (P &gt; 0.1). The self-care ability, the nature of the disease, and whether the patient was treated for chemotherapy were the independent influencing factors of the patient’s quality of life, and the difference was statistically significant (P &lt; 0.001). Conclusion: Patients with advanced lung cancer have different degrees of anxiety and depression, and their quality of life is affected by many factors, which are mainly related to the patient’s self-care ability, the nature of the disease, and whether they received chemotherapy.

The effectiveness of exercise interventions on psychological distress in patients with lung cancer: a systematic review and meta-analysis.

To assess the effectiveness of exercise interventions on psychological distress in lung cancer patients and how this effectiveness varies by cancer stage, treatment, intervention type (exercise/with other interventions), exercise mode, duration, and sustained effects over time. Randomized controlled trials (RCTs) investigating exercise effects on psychological distress were included. Exclusion criteria were studies with less than 50% lung cancer patients, those on pharmacotherapy/psychotherapy, and studies focused solely on breathing exercises. Data sources included PubMed, Embase, MEDLINE, CINAHL, and Scopus. Reporting followed PRISMA 2020 guidelines, with analysis via Review Manager 5.4, and quality assessed using Cochrane RoB 2. Twenty-two studies with 1524 participants were selected from 611 articles. All intervention groups were compared to usual care. Meta-analysis, including 11 studies, showed significant reductions in anxiety (SMD = - 0.52, 95% CI = - 0.94 to - 0.09, p = .02) and depression (SMD = - 0.55, 95% CI = - 0.89 to - 0.21, p = .001). The subgroup revealed that early-stage patients, surgery alone, engaging in aerobic exercise (with other exercise modes) or combined interventions showed greater effectiveness in reducing anxiety and depression. Regarding sustained effects, exercise interventions showed a significant medium-term effect on reducing anxiety. Exercise interventions show promise in reducing psychological distress among lung cancer patients. However, further research is needed to optimize these interventions and explore their long-term effects. The effectiveness of exercise interventions on psychological distress in lung cancer patients varies by cancer stage, treatment, and intervention type, supporting the use of tailored programs.

Lung cancer screening: Real screening site data, Vojvodina, Serbia

Abstract Background Lung cancer (LC) is the top cause of cancer-related deaths globally and in Serbia, often diagnosed in advanced stage of disease with when 5-year survival is 10% to 20%. LC screening with low-dose CT (LDCT) can decrease LC mortality and overall mortality. The first pilot LC screening program in Serbia started in the Institute for Pulmonary Diseases of Vojvodina in September 2020. The main objective of this study was to analyze LC patient characteristics according to their screening status. Methods This retrospective study utilized LC hospital registry data from September 2020 to December 2023, including gender, age at diagnosis, settlement area, smoking habits, cancer histological type, TNM classification, disease stage (1-4), and data on participation in LC screening. Group differences were assessed using chi-square and Student’s t-tests, with analyses conducted in SPSS v24.0. Results During observed period from a total of 4649 LC cases 2948 (63.4%) were males, and 73 (1.6%) were included in LC screening. Average age of all LC patients was 66 years, without differences between groups (p = 0.778). Significant differences between groups by gender were find (p = 0.042). Non-screened LC patients were significantly common males compared to females (63.6% vs 36.4%), while among screened difference by gender were lower (52.1% vs 47.9%, respectively). Screened compared to non-screened LC patients have significantly lower percentage of SCLC (9.6% vs 19.1%), and higher percentage of NSCLC (90.4% vs 80.9%), (p = 0.040). According to LC stage, screened compared to non-screened patients were significantly common diagnosed in stage I of disease (45.8% vs 7.8%), and significantly less common in higher LC stages; stage IIIB (11.1% vs 22.5%), and in stage IV (22.2% vs 45.7%), (p &amp;lt; 0.001). Conclusions LC screening with LDCT is proven secondary preventive measure with significant influence on decreasing LC mortality by increasing number of LC patients in early stages of disease. Key messages • Lung cancer screening with low-dose CT significantly increases early-stage diagnoses, improving survival chances. • Population strategies to prevent smoking and screening programs for high-risk groups are needed to reduce lung cancer incidence and mortality rates in Serbia.

Knockdown of circ_0006225 overcomes resistance to cisplatin and suppresses growth in lung cancer by miR-1236-3p/ANKRD22 axis.

Cisplatin-based chemotherapy is the mainstay of therapeutic agents for lung cancer. Hence, we investigated the role and mechanism of circ_0006225 in tumorigenesis and cisplatin resistance in lung cancer. Levels of circ_0006225, microRNA (miR)-1236-3p and ankyrin repeat domain 22 (ANKRD22) were detected. Cell cisplatin (DDP) sensitivity and growth were determined by Cell Counting Kit-8, cell colony formation, 5-ethynyl-2'-deoxyuridine, and murine xenograft assays, respectively. A high level of circ_0006225 in lung cancer tissues and cells with cisplatin resistance was observed. Circ_0006225 deletion elevated cisplatin sensitivity and constrained proliferation in DDP-resistant lung cancer cells in vitro. Mechanistically, Circ_0006225 was confirmed to modulate ANKRD22 by sequestering miR-1236-3p. Furthermore, the suppressive effects of circ_0006225 downregulation on cisplatin resistance and proliferation in DDP-resistant lung cancer cells were reversed by miR-1236-3p inhibition or ANKRD22 overexpression. Besides that, circ_0006225 silencing also repressed cisplatin resistance and tumor growth in lung cancer in vivo. In conclusion, knockdown of circ_0006225 restrained the growth and reduced cisplatin resistance in lung cancer by the miR-1236-3p/ANKRD22 axis, suggesting a better effective therapeutic target for overcoming cisplatin resistance in lung cancer patients.

Biosynthesis of pH-Responsive Mesoporous Silica Nanoparticles from Cucumber Peels for Targeting 3D Lung Tumor Spheroids.

Lung adenocarcinoma is considered to be one of the primary causes of cancer-related deaths globally. Conventional treatments, such as chemotherapy and radiation therapy taken together, have not significantly lowered mortality rates. Repositioning of authorized anticancer medications supported by nanotechnology has therefore emerged as an effective strategy to close such gaps. In this context, mesoporous silica nanoparticles (MSNs) were biosynthesized from cucumber peels and were loaded with doxorubicin, a common anticancer drug to form doxorubicin-bound mesoporous silica nanoparticles (DMSNs). The study addresses a sustainable method for turning waste materials into MSNs, which can be used to create multifunctional nanosystems. The therapeutic module (DMSNs) was designed specifically to target 2D monolayer cells and 3D tumor spheroids of lung adenocarcinoma cancer. The DMSNs demonstrated notable antiproliferative activity and effective intracellular localization in addition to being biocompatible and innately fluorescent. Subsequent investigations revealed significant antibacterial activity against Staphylococcal infection, which is primarily prevalent in lung cancer patients. Thus, the developed MSNs held promising potential for anticancer drug delivery systems and have antibacterial potential to treat bacterial infections in patients with lung cancer. Furthermore, the cucumber peel-mediated synthesis of MSNs could also aid in the management of food waste and promote the adoption of the waste-to-health paradigm for sustainable solutions.

Minimum Dataset of Lung Cancer Patients: An Initial Step Towards Developing a Web-Based Personal Health Record

Background: Personal Health Records (PHR), which utilize advanced health information technology tools, play a crucial role in patient self-management and improving the control of chronic diseases such as lung cancer. To optimize the design of these systems, it is essential to determine the necessary data elements. Objectives: This study aims to identify the minimum dataset required for designing a web-based PHR for lung cancer patients. Methods: This descriptive, cross-sectional research was conducted in 2023. Initially, a lung cancer dataset was extracted through text analysis. In the next phase, a proposed minimum lung cancer dataset was formulated into a questionnaire containing 18 data groups, including 126 data elements. The dataset underwent expert validation in two phases using the Delphi technique. Data analysis was performed using SPSS version 26, with descriptive statistics employed. Results: The minimum web-based PHR dataset for lung cancer patients, consisting of 18 data groups (112 data elements), includes demographics, insurance information, emergency contact details, patient symptoms, tumor-related data, physician details, treatment information, patient-reported measurements, personal medical history, history of procedures and surgeries, visits, allergies, family history, medication information, test results, imaging data, dietary information, and educational materials. Conclusions: Based on the study findings, it is recommended that lung cancer data management encompass not only routine information but also additional dimensions such as allergies, tumor-related information, and dietary details. Collecting comprehensive and complete data can significantly enhance the treatment process and post-treatment follow-up.

Evaluation of cfDNA fragmentation characteristics in plasma for the diagnosis of lung cancer: A prospective cohort study.

Lung cancer is one of the most prevalent cancers worldwide, yet only approximately 16% of patients are diagnosed in early stage, highlighting the urgent need for novel, highly accurate detection models. In our study, patients with suspected lung cancer or lung disease, as identified through radiographic imaging, along with healthy individuals, were consecutively recruited from Beijing Chest Hospital. Circulating free DNA (cfDNA) was extracted from plasma samples, and low-depth whole-genome sequencing was performed to identify fragmentomic features for model construction. A total of 265 participants were prospectively enrolled, comprising 124 lung cancer patients and 141 noncancer individuals. The model we developed was based on four cfDNA fragmentation characteristics, including 20-bp breakpoint nucleotides motif, fragmentation size coverage, fragmentation size distribution, and copy number variation. In an independent test cohort, the model achieved an area under the curve (AUC) of 0.861 (95% CI: 0.781-0.942) and demonstrated a sensitivity of 70% (95% CI: 53.5%-83.4%) at a specificity of 89.4% (95% CI: 76.9%-96.5%). Notably, the model was also effective in detecting early-stage cancer, with an AUC of 0.808 (95% CI: 0.69-0.925). In summary, our lung cancer detection model shows strong screening capabilities by leveraging four cfDNA fragmentation characteristics, exhibiting robust performance in early cancer diagnosis.

Prevalence and Risk Factors of Psychological Distress in Patients With Early-Stage Lung Cancer During Preoperative Period: A Cross-Sectional Study.

This study aims to investigate the prevalence of significant psychological distress and identify risk factors associated with it among early-stage lung cancer patients in the preoperative period. Lung cancer is a major cause of cancer deaths worldwide, with low survival rates and significant psychological distress. While much research has focused on distress in advanced-stage patients, less is known about the prevalence and risk factors of psychological distress in early-stage lung cancer patients before surgery. A cross-sectional study. The study included 427 early-stage lung cancer patients preparing for surgery. Researchers used a study-specific questionnaire to gather general information and employed the Distress Management Screening Measurement, Patient Health Questionnaire-9 and Generalised Anxiety Disorder-7 to assess personal situations and psychological distress levels. Statistical analyses investigated distress across various patient characteristics and examined correlations with anxiety and depression. Binary logistic regression identified significant predictors of psychological distress. The study found that 41.9% of early-stage lung cancer patients experienced significant psychological distress preoperatively, with an average score of 3.31 ± 2.18. Psychological distress was significantly positively correlated with depression (r = 0.474, p < 0.001) and anxiety (r = 0.591, p < 0.001). Significant risk factors for psychological distress included pulmonary nodules (OR = 2.884, 95% CI: 1.496-5.559), smoking history (OR = 2.092, 95% CI: 1.016-4.306) and chronic diseases (OR = 2.013, 95% CI: 1.073-3.776). Early-stage lung cancer patients often experience a high incidence of clinically significant psychological distress during the preoperative period, strongly associated with depression and anxiety. Adverse factors contributing to psychological distress include multiple indeterminate pulmonary nodules, smoking history and concurrent chronic diseases. Routine screening for psychological distress in these patients is recommended, along with personalised interventions and self-management strategies to help alleviate their distress during the perioperative period.

Super-resolution reconstruction of time-resolved four-dimensional computed tomography (TR-4DCT) with multiple breathing cycles based on TR-4DMRI.

Respiratory motion irregularities in lung cancer patients are common and can be severe during multi-fractional (∼20 mins/fraction) radiotherapy. However, the current clinical standard of motion management is to use a single-breath respiratory-correlated four-dimension computed tomography (RC-4DCT or 4DCT) to estimate tumor motion to delineate the internal tumor volume (ITV), covering the trajectory of tumor motion, as a treatment target. To develop a novel multi-breath time-resolved (TR) 4DCT using the super-resolution reconstruction framework with TR 4D magnetic resonance imaging (TR-4DMRI) as guidance for patient-specific breathing irregularity assessment, overcoming the shortcomings of RC-4DCT, including binning artifacts and single-breath limitations. Six lung cancer patients participated in the IRB-approved protocol study to receive multiple T1w MRI scans, besides an RC-4DCT scan on the simulation day, including 80 low-resolution (lowR: 5×5×5mm3) free-breathing (FB) 3D cine MRFB images in 40s (2Hz) and a high-resolution (highR: 2×2×2mm3) 3D breath-hold (BH) MRBH image for each patient. A CT (1×1×3mm3) image was selected from 10-bin RC-4DCT with minimal binning artifacts and a close diaphragm match (<1cm) to the MRBH image. A mutual-information-based Freeform deformable image registration (DIR) was used to register the CT and MRBH via the opposite directions (namely F1: and F2: ) to establish CT-MR voxel correspondences. An intensity-based enhanced Demons DIR was then applied for , in which the original MRBH was used in D1: , while the deformed MRBH was used in D2: . The deformation vector fields (DVFs) obtained from each DIR were composed to apply to the deformed CT (D1) and original CT (D2) to reconstruct TR-4DCT images. A digital 4D-XCAT phantom at the end of inhalation (EOI) and end of exhalation (EOE) with 2.5cm diaphragmatic motion and three spherical targets (ϕ=2, 3, 4cm) were first tested to reconstruct TR-4DCT. For each of the six patients, TR-4DCT images at the EOI, middle (MID), and EOE were reconstructed with both D1 and D2 approaches. TR-4DCT image quality was evaluated with mean distance-to-agreement (MDA) at the diaphragm compared with MRFB, tumor volume ratio (TVR) referenced to MRBH, and tumor shape difference (DICE index) compared with the selected input CT. Additionally, differences in the tumor center of mass (|∆COMD1-D2|), together with TVR and DICE comparison, was assessed in the D1 and D2 reconstructed TR-4DCT images. In the phantom, TR-4DCT quality is assessed by MDA=2.0±0.8mm at the diaphragm, TVR=0.8±0.0 for all tumors, and DICE=0.83±0.01, 0.85±0.02, 0.88±0.01 for ϕ=2, 3, 4cm tumors, respectively. In six patients, the MDA in diaphragm match is -1.6±3.1mm (D1) and 1.0±3.9mm (D2) between the reconstructed TR-4DCT and lowR MRFB among 18 images (3 phases/patient). The tumor similarity is TVR=1.2±0.2 and DICE=0.70±0.07 for D1 and TVR=1.4±0.3 (D2) and DICE=0.73±0.07 for D2. The tumor position difference is |∆COMD1-D2|=1.2±0.8mm between D1 and D2 reconstructions. The feasibility of super-resolution reconstruction of multi-breathing-cycle TR-4DCT is demonstrated and image quality at the diaphragm and tumor is assessed in both the 4D-XCAT phantom and six lung cancer patients. The similarity of D1 and D2 reconstruction suggests consistent and reliable DIR results. Clinically, TR-4DCT has the potential for breathing irregularity assessment and dosimetry evaluation in radiotherapy.

Determinants of immune checkpoint inhibitor use and factors linked to neurological adverse events in Korean lung cancer.

Aim: Studies on immune checkpoint inhibitor (ICI)-related potential neurological adverse events (pNAEs) in Korean lung cancer (LC) patients are scarce. We aimed to examine ICI prescription trends from 2018 to 2022, patient characteristics and factors associated with ICI prescription or concurrent pNAEs in LC.Research design & methods: This observational, cross-sectional study of Korean LC patients investigated four ICIs (pembrolizumab, nivolumab, atezolizumab and durvalumab). The annual ICI prescription rate was calculated by dividing the number of LC patients prescribed ICIs with the total annual number of LC patients. Factors associated with ICI prescriptions or concurrent pNAEs were assessed.Results: The annual ICI prescription rate increased from 3.29% to 9.74% (average: 6.20%). Higher Charlson Comorbidity Index (CCI) scores were associated with more ICI prescriptions (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.07-1.08). Targeted therapy was associated with fewer prescriptions (OR: 0.45; 95% CI: 0.41-0.49). The anti-programmed cell death protein 1 (anti-PD-1) prescription rate was higher in patients with concurrent pNAEs than those without pNAEs (53.09% vs. 50.84%), and this was associated with higher pNAEs prevalence (OR: 1.10; 95% CI: 1.03-1.18).Conclusion: ICI prescription for LC has increased in Korea, CCI and anti-PD-1 increased pNAEs prevalence.

Cardiovascular events in estimated glomerular filtration rate-mutation non-small-cell lung cancer patients on osimertinib

ObjectivesThere have been cases of cardiotoxicity induced by osimertinib in patients with non-small-cell lung cancer (NSCLC). However, limited data exist for a comprehensive cardiotoxicity profile analysis for osimertinib use in...

Novel risk score for predicting acute cardiovascular and cerebrovascular events after chest radiotherapy in patients with breast or lung cancer.

Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0-2), intermediate (3-5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.

The oncogenic axis YAP/MYC/EZH2 impairs PTEN tumor suppression activity enhancing lung tumorigenicity

The tumor suppressor PTEN (phosphatase and tensin homolog deleted in chromosome 10) is genetically deleted or downregulated in many cancer types. Loss of PTEN protein expression is frequently found in lung cancer while genetic alterations are less abundant. PTEN expression is regulated at multiple genetic and epigenetic levels and even partial reduction of its expression increases cancer occurrence. We show that YAP and TAZ cooperate with EZH2, and MYC to transcriptionally repress onco-suppressor genes, including PTEN, in non-small cell lung cancer (NSCLC) cells. YAP/TAZ-EZH2-MYC transcriptional regulators form a nuclear complex that represses PTEN transcription, while their combinatorial targeting restores PTEN expression, attenuates NSCLC cell growth, and prevents compensatory responses induced by single treatments. Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.

Real-world treatment patterns, biomarker testing, and clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era.

Treatment for first-line (1L) metastatic non-small cell cancer (mNSCLC) changed with the introduction of immunotherapy. We describe treatment utilization and clinical outcomes in a real-world mNSCLC cohort in a 2.7-million-member state-mandated health provider. Newly diagnosed mNSCLC patients initiating systemic anti-cancer treatment (January 2017-December 2020) were identified from the National Cancer Registry. Real-world time on treatment (rwToT) was defined as the length of time between the first and last administration date of treatment. Real-world overall survival (rwOS) was estimated using Kaplan-Meier analysis. Outcomes were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021). Among 843 patients, 85% had adenocarcinoma (NSQ) and 15% had squamous cell carcinoma (SQ) histology: of these, 43% and 26% were women, median age was 67 and 69 years, and 55% and 48% had 0-1 ECOG performance status, respectively (missing: 27% and 30%, respectively). Median follow-up for the entire cohort was 27.1 months (95% CI: 24.7-29.6). NSQ patients with no known EGFR/ALK/ROS1 aberrations received PD-1 inhibitor monotherapy (PDM) (N = 147) or combination (PDC) (N = 194) or platinum-based chemotherapy (PBC, N = 133). Median rwToT was 4.5 (95% CI: 3.5-7.6), 5.2 (95% CI: 4.6-7.6), and 2.3 (95% CI: 2.1-3.0) months, respectively; for the subgroup of patients with ECOG PS 0-1, rwToT was 9.4 (95% CI: 5.0-20.8), 7.1 (95% CI: 5.0-10.1), and 2.9 (95% CI: 2.2-4.1) months, respectively. Median rwOS from 1L was 12.5 (95% CI: 9.9-17.9), 14.8 (95% CI: 10.5-19.4), and 9.1 (95% CI: 7.1-11.5) months; for the subgroup of patients with ECOG PS 0-1, median rwOS was 25.1 [95% CI: 14.9-not reached (NR)], 17.6 (95% CI: 14.3-NR), and 11.3 (95% CI: 9.2-21.3) months, respectively. For ECOG PS 0-1 and PD-L1 ≥50% patients, median rwOS was 25.1 months (95% CI: 13.9-NR) and NR for PDM and PDC, respectively. For ECOG PS 0-1 and PD-L1 <50% patients, median rwOS was 14.3 (95% CI: 10.1-NR) and 11.2 (95% CI: 9.1-21.3) months for PDC and PBC, respectively. Our real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment.

Cancer-associated Fibroblasts (CAFs) Regulate Lung Cancer Malignant Progression by Transferring SERPINE2 (PN1) Via Exosomes.

Cancer-associated fibroblasts (CAFs), one of the most abundant stromal cell types in tumor microenvironment (TME), have been a potential target for cancer treatment such as lung cancer. However, the underlying mechanism by which CAFs promote lung cancer progression remains elusive. We obtained primary CAFs, normal fibroblasts (NFs) and their exosomes, constructed protease nexin-1 (PN1) stably silenced or over-expressed CAFs cells using lentivirus. Bioinformatics was used to obtain the expression of PN1 in lung cancer and normal tissues, the relationship with overall survival, and the enriched pathways. The MTT assays and Transwell assays were performed to detect the proliferation, migration, and invasion abilities of lung cancer cells after treatments. Western blotting, qRT-PCR, immunohistochemistry, and xenograft models were used to illustrate how CAFs functions in lung cancer progression via exosomes. CAFs-derived exosomes, in which PN1 was higher expressed compared with NFs-derived ones, promoted effectively the proliferation, migration, and invasion of lung cancer cells A549 and H1975. Meanwhile, the expression of PN1 expressed higher in lung cancer tissues compared with normal ones, and was negatively associated with the overall survival rate of lung cancer patients. More importantly, over-expressing or silencing PN1 in A549 and H1975 could also promote or inhibit cell proliferation, migration, and invasion correspondingly. Furthermore, treated with PN1 over-expressed CAFs-derived exosomes, the lung cancer cells proliferation, migration, and invasion varied positively, and accompanied by activation of Toll-like and NF-κB signaling pathways. However, this phenomenon can be reversed by AN-3485, an antagonist of Toll-like pathway. Finally, over-expressing PN1 leads to an accelerated tumor growth by increasing the expression of proliferation biomarker Ki67 and activation of NF-κB signaling pathway in vivo. CAFs promoted lung cancer progression by transferring PN1 and activating Toll-like/NF-κB signaling pathway via exosomes.

Molecular docking and spectroscopic exploration (FT‐IR, FT‐Raman) with HOMO–LUMO, ADMET, and 5,7‐dihydroxy‐2‐(4‐hydroxyphenyl) chroman‐4‐one against lung cancer: A potential uptake B‐RAF inhibitor

AbstractNaringenin has been proven to inhibit cell proliferation, which has anticancer properties. The role of Naringenin molecule in lung cancer and its processes are yet unknown. Naringenin is chemically called as 5,7‐dihydroxy‐2‐(4‐hydroxyphenyl) chroman‐4‐one, which was optimized geometrical parameters analysis such as bond length, bond angle and torsion angle were analyzed from Naringenin by utilizing Gaussian 09 W program. Characterizations of Naringenin analyzed by B3LYP density functional theory with basis set 6–311G (d,p). The energy value of Naringenin molecules are analyzed with (ground state) HOMO value −4.616, LUMO value for −0.169 (first excited state) energies and also predicted by energy cap value is 4.446. ADMET and drug likeness of the title compound was predicted, it's qualified with the Lipinski's rule of five. Naringenin molecular structural changes, distribution and also its reactive site investigated with MEP (Molecular Electrostatic Potential) analyses spans from −0.118eO to 0.118eO. The density of state (DOS) used to know molecular orbital contribution for selected compound. It was determined that Naringenin molecule in the active site of B‐RAF inhibitor (PDB code: 4MNF) has a binding energy of −8.9 based on a docking analysis and conformational changes. From this study, this drug will be expected to undergo essential future chemotherapy agent for lung cancer patient.