Lung Adenocarcinoma Cancer Research Articles

CircRNA circ-PDCD11 is highly expressed in lung large-cell carcinoma and predicts poor survival

Background Circ-PDCD11 (hsa_circ_0019853, 461 bp) has been characterized as an oncogenic circRNA in breast cancer, while its function in other cancers is unclear. In this study, we explored the role of circ-PDCD11 in lung cancer. Methods Plasma samples were obtained from patients with lung large-cell carcinoma (LLCC, n = 40), lung squamous cell carcinoma (LSCC, n = 40), lung adenocarcinoma (LA, n = 40) and small-cell lung cancer (SCLC, n = 40) as well as healthy controls (Control, n = 40). Paired tumor and nontumor tissue samples were obtained from all patients. Expression of circ-PDCD11 in these samples was determined by RT-qPCR. The role of plasma circ-PDCD11 in the diagnosis of LLCC was analyzed with ROC curve. A five-year follow-up was performed to analyze the role of plasma circ-PDCD11 in the prognosis of LLCC. Results Plasma circ-PDCD11 was specifically upregulated in LLCC but not in other lung cancer types, compared to the controls. Increased circ-PDCD11 expression in tumor tissues compared to nontumor tissues was only observed in LLCC patients but not in other lung cancer types. Increased plasma circ-PDCD11 levels effectively separated LLCC patients from patients with other types of cancers. High plasma circ-PDCD11 levels were closely correlated with poor survival of LLCC patients. Plasma circ-PDCD11 levels were closely correlated with tumor metastasis, but not tumor size of LLCC. Conclusion CircRNA circ-PDCD11 is highly expressed specifically in LLCC and predicts poor survival.

The Association of Visibility and Adenocarcinoma Lung Cancer in Southern Taiwan

Background/Aim Studies on association between lung cancer and long-term exposure to air pollution are limited due to the unavailability of air pollution data. The study aims to assess association of visibility, a proxy indicator of long-term air pollution exposure, with adenocarcinoma lung cancer. Methods Our study area is in southern Taiwan, an industrial area with 2.7 million people in 5.7 thousand km². Annual lung cancer incidence data with the ICD-O-3 codes from C34.0-C34.9 were obtained from Taiwan Cancer Registry (TCR) from 1997 to 2018. Age-adjusted incidence of lung cancers were standardized by the WHO 2000 world standard population. Hourly atmospheric visibility data from 1961 to 2022 were obtained from Taiwan Central Weather Bureau. 30-years moving averages were then calculated from 1967 onward to represent long-term visibility in the study area. Linear regression models were employed to estimate associations of 30-years averaging visibility annual age-adjusted lung cancers incidence for both adenocarcinoma and non-adenocarcinoma from 1997 to 2018. Results From 1997 to 2018, southern Taiwan's adenocarcinoma lung cancer incidence increased from 8.93 to 25.81 per 100,000 population, while non-adenocarcinoma incidence decreased from 14.61 to 10.41 per 100,000 population. The 30-years averaged visibility in the study area declined from 14.90 km to 7.65 km in the same period. Reducing visibility is significantly associated adenocarcinoma lung cancer, with a 2.43% (95% confidence interval [CI]: 2.77-2.11, adjusted R2 value: 0.92) increase in incidence by 1 km decrease in visibility during this period. Such associations exist for both females and males with increasing incidence of 2.57% (95% CI: 2.92-2.22, adj R2: 0.92) and 2.32% (95% CI: 2.69-1.95, adj R2: 0.89) by 1 km visibility reduction, respectively. By contrast, visibility reduction was not associated with increased in non-adenocarcinoma incidence. Conclusions Long-term visibility reduction is associated with increase in adenocarcinoma lung cancer incidence but not with non-adnocarcinoma.

A combined iterative sure independence screening and Cox proportional hazard model for extracting and analyzing prognostic biomarkers of adenocarcinoma lung cancer

The selection of significant biomarkers is essential in researching cancer diagnosis and treatment. The independence screening method works substantively to select crucial features based on the conditional marginal selection method. But it may pretermit the concoction effect of some marginally less essential covariates. We aim to obtain a significant biomarker-specific prediction on overall survival to know their survival and death risk. In this work, an iterative sure independence screening (ISIS) scheme has been applied to extract features from the high-dimensional dataset of adenocarcinoma lung cancer. Conventional and Bayesian approaches of the Cox proportional hazard (CPH) model have been used for analyzing the data to provide interpretation and conclusions about survival estimates. The accelerated failure time model is also used as an alternative to the CPH model. A forest plot is employed to show the graphical representation of the meta-analysis of the study design. Utilizing ISIS, we selected up to 20 relevant features From the entire dataset of adenocarcinoma lung cancer; some of them are liable to produce a positive hazard ratio greater than 1, and some are less than 1. The P values associated with the selected biomarkers imply their statistical significance. Fourteen biomarkers have been identified with a hazard ratio of less than 1; the remaining 20 biomarkers are greater than 1. These 14 biomarkers produce less risk of death for patients with adenocarcinoma lung cancer, and the remaining six biomarkers result in a high risk of death from adenocarcinoma lung cancer.

1152P Lung cancer metastasis patterns and racial disparities: A SEER database population study 2010–2018

Metastatic disease at the time of lung cancer diagnosis portends poor outcomes. Differences in metastasis among Caucasians (C) and African-Americans (AA) need elucidation. We analyzed metastasis patterns in C and AA in small cell lung cancer (SCLC), squamous cell lung cancer (SQC), lung adenocarcinoma (LA), and large cell lung cancer (LCC).

906P A pilot study of a lung cancer screening program with low-dose computed tomography in high-risk individuals in Greece

Greece is one of the European countries with the highest prevalence of smoking. Low-dose computed tomography (LDCT) has been proposed as a useful tool for the early detection of lung cancer, with the potential to reduce death rates. Given the fact that Greece has no National Lung Cancer Screening program, the pilot REGISTRY study was designed to assess the effects of baseline screening with LDCT in high-risk individuals. From January 2016 to March 2022, 1500 individuals aged > 45 years with smoking history of at least 15 pack-years, were recruited in the study. Former smokers needed to quit within 15 years from study entry to be eligible. Each participant was advised to undergo annual screening with LDCT for ten years and the evaluation was based on the updated NCCN guidelines. A high rate of adherence to screening (90.1%) was reported. The median age of participants was 63 years and the number of pack years ranged from 15 to 72 (median 30 years). In total, 697 subjects (46,4%) reported at least one comorbidity including hypertension, diabetes mellitus, COPD and/or prior cancer. The rate of positive screening tests was 0,66% (10 of 1500 patients). Eight patients were diagnosed with cancer at baseline LDCT, while the rest within two years from initiation of screening. All ten patients were diagnosed with non-small cell lung cancer (adenocarcinoma=5 and squamous cell carcinoma N=5). All patients underwent surgery. Seven patients were diagnosed with stage I, two with stage II and one with stage III disease. Real-world data from this pilot study in Greece are concordant with large randomized phase III screening trials and confirm the utility of LDCT as a potent strategy for the early detection of lung cancer. A National Lung Cancer screening program should become a priority for Greek health policy makers.

79P Molecular characterization of KRAS NSCLC all stages: A single-center cohort

Kirsten rat sarcoma viral oncogene mutation (KRASm) is detected in approximately 25% of non-small cell lung cancer (NSCLC) adenocarcinoma patients (pts). As Next-generation sequencing (NGS) has been increasingly employed, diverse KRASm subtypes (subt) with different prognoses, incidences of co-mutations and characteristics have been described.

HER2 drives lung fibrosis by activating a metastatic cancer signature in invasive lung fibroblasts.

Progressive tissue fibrosis, including idiopathic pulmonary fibrosis (IPF), is characterized by excessive recruitment of fibroblasts to sites of tissue injury and unremitting extracellular matrix deposition associated with severe morbidity and mortality. However, the molecular mechanisms that control progressive IPF have yet to be fully determined. Previous studies suggested that invasive fibroblasts drive disease progression in IPF. Here, we report profiling of invasive and noninvasive fibroblasts from IPF patients and healthy donors. Pathway analysis revealed that the activated signatures of the invasive fibroblasts, the top of which was ERBB2 (HER2), showed great similarities to those of metastatic lung adenocarcinoma cancer cells. Activation of HER2 in normal lung fibroblasts led to a more invasive genetic program and worsened fibroblast invasion and lung fibrosis, while antagonizing HER2 signaling blunted fibroblast invasion and ameliorated lung fibrosis. These findings suggest that HER2 signaling may be a key driver of fibroblast invasion and serve as an attractive target for therapeutic intervention in IPF.

Evaluation of thoracic diseases with computed tomography guided biopsy

Computed tomography (CT) guided percutaneous procedures like the fine needle aspiration cytology (FNAC) and fine needle aspiration biopsy (FNAB) are reliable techniques for diagnosing various thoracic diseases. These modalities are used for diagnosis in suspicious lung, pleural, mediastinal and vertebral and pulmonary lesions.The aim. We conducted a study in a Pulmonary Medicine Department of tertiary care hospital to study the efficacy and safety of CT guided FNCA/FNAB in thoracic diseases.Methods. A retrospective study was conducted at a tertiary care center with Information and Ethics committee permission within a total duration of two years. The study included patients presenting with following: 1) mediastinal mass lesions, 2) pulmonary solitary pulmonary nodules/masses, 3) pulmonary cavity, cyst and consolidation of undiagnosed etiology, 4) pleural mass, nodules, loculated collections, 5) extra-pulmonary and spinal tuberculosis suspects with pre/paravertebral abscess. Procedure details, radiological images and pathological and microbiological reports were retrieved from case record book of patients available in department.Results. Study population consisted of 108 patients. Neoplastic diseases were 85 (78.70%) and Non- neoplastic diseases 23 (21.29%). In neoplastic diseases 78.82% patients had lung Cancer of which 85.07% non small cell carcinoma and 14.92% small cell lung cancer. Out of non small cell lung cancer adenocarcinoma of lung was the commonest. The most common non neoplastic diseases was tuberculosis. CT guided biopsy procedure was performed without any complications in 61.11%. The most common complication was pneumothorax (27.77%). The yield of CT guided biopsy was 98.14%.Conclusion. Percutaneous CT-guided lung biopsy is an effective, highly accurate, and safe method of obtaining tissue for the diagnosis of indeterminate pulmonary lesions especially in neoplastic diseases and tuberculosis.

New Derivatives of 5-((1-Methyl-Pyrrol-2-yl) Methyl)-4-(Naphthalen-1-yl)-1,2,4-Triazoline-3-Thione and Its Coordination Compounds with Anticancer Activity.

A new ligand 5-((1-methyl-pyrrol-2-yl) methyl)-4-(naphthalen-1-yl)-1,2,4-triazoline-3-thione (C15) and its metal complexes with formulae: Mn(C15)Cl2MeOH (1), Fe(C15)Cl2MeOH (2), Ni(C15)Cl2MeOH (3), Cu(C15)2Cl2 (4) and Zn(C15)4Cl2 (5) have been synthesized. The C15 ligand and complexes were characterized by NMR, elemental analysis, FT-IR, EPR, magnetic and TGA studies. The anticancer activities of the organic ligand (C15) and complexes (1–5) were evaluated against human colon adenocarcinoma (HT29) and human lung (A549) cancer cell lines. The complex (1) exhibited potential activity at concentration of 794.37 μM (A549) and 654.31 μM (HT29) in both cancer cells. The complex (3) showed significant activity against the HT29 cancer cell line with an IC50 value of 1064.05 μM. This article highlights some of the metals that have become important in the development of new coordination complexes and the treatment of cancer. Additionally, for C15, the toxicity was predicted by ADMET analysis and molecular docking.

Investigating and Modeling the Differential DNA Methylation for Early Lung Adenocarcinoma Diagnosis

Background: Aberrant DNA methylations serve as rich sources of diagnostic biomarkers, but a further improvement in their accuracy and clinical utility is warranted. Methods: Large panel bisulfite sequencing was performed on paired normal and stage I/IV tumors from 226 lung adenocarcinoma cancer patients to characterize the differentially methylated regions (DMRs). Results: Random forest model achieved high prediction accuracy (sensitivity 96% and specificity 97.56%) to separate normal controls from both early and advanced cancer samples, which is superior to most previous prediction models tested in lung adenocarcinoma. Conclusion: Our results suggest that combining the random forest model with targeted bisulfite sequencing have great clinical potential to accurately predict and diagnose lung adenocarcinoma early during cancer screening.

Epidemiological characteristics and risk factors of lung adenocarcinoma: A retrospective observational study from North China.

BackgroundThe main aim of the study was to determine the risk factors of lung adenocarcinoma and to analyze the variations in the incidence of lung adenocarcinoma according to time, sex, and smoking status in North China.MethodsPatients with lung cancer in local household registries diagnosed and treated for the first time in the investigating hospital were enrolled from 11 cities in North China between 2010 and 2017. Baseline characteristics and tumor-related information were extracted from the patients’ hospital medical record, clinical course records, and clinical examination. Some of the variables, such as smoking, alcohol consumption, medical history, and family history of cancer, were obtained from interviews with the enrolled patients. The statistical method used were the chi-square test and multi-factor logistic regression analysis. The time trend was statistically analyzed using Joinpoint regression models, and p values were calculated.ResultsA total of 23,674 lung cancer cases were enrolled. People in severely polluted cities were at higher risk for lung adenocarcinoma (p < 0.001). Most patients with lung adenocarcinoma had no history of lung-related diseases (p = 0.001). Anatomically, lung adenocarcinoma was more likely to occur in the right lung (p < 0.001). Non-manual labor workers were more likely to develop from lung adenocarcinoma than manual workers (p = 0.015). Notably, non-smokers were more likely to develop lung adenocarcinoma than smokers (p < 0.001). The proportion of lung adenocarcinoma increased significantly in Hebei Province (p < 0.001). Among non-smokers, the proportion of lung adenocarcinoma showed a higher rise than in smokers (p < 0.001).ConclusionsLung adenocarcinoma is the most common histological type of lung cancer in North China (Hebei Province), and the proportion of lung adenocarcinoma is increasing, especially among non-smokers. Lung adenocarcinoma is more common in women, severely polluted cities, individuals with no history of lung-related diseases, in the right lung, and in non-smokers. These can serve as a great guide in determining the accuracy of lung adenocarcinoma high-risk groups and lung cancer risk assessment models.

ASURAT: functional annotation-driven unsupervised clustering of single-cell transcriptomes.

MotivationSingle-cell RNA sequencing (scRNA-seq) analysis reveals heterogeneity and dynamic cell transitions. However, conventional gene-based analyses require intensive manual curation to interpret biological implications of computational results. Hence, a theory for efficiently annotating individual cells remains warranted.ResultsWe present ASURAT, a computational tool for simultaneously performing unsupervised clustering and functional annotation of disease, cell type, biological process and signaling pathway activity for single-cell transcriptomic data, using a correlation graph decomposition for genes in database-derived functional terms. We validated the usability and clustering performance of ASURAT using scRNA-seq datasets for human peripheral blood mononuclear cells, which required fewer manual curations than existing methods. Moreover, we applied ASURAT to scRNA-seq and spatial transcriptome datasets for human small cell lung cancer and pancreatic ductal adenocarcinoma, respectively, identifying previously overlooked subpopulations and differentially expressed genes. ASURAT is a powerful tool for dissecting cell subpopulations and improving biological interpretability of complex and noisy transcriptomic data.Availability and implementationASURAT is published on Bioconductor (https://doi.org/10.18129/B9.bioc.ASURAT). The codes for analyzing data in this article are available at Github (https://github.com/keita-iida/ASURATBI) and figshare (https://doi.org/10.6084/m9.figshare.19200254.v4).Supplementary information Supplementary data are available at Bioinformatics online.

Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma

BackgroundCancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated.MethodsIn this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells.ResultsThe results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis.ConclusionsIn conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.

GANT61/BI-847325 combination: a new hope in lung cancer treatment

Despite the huge efforts employed to implement novel chemotherapeutic paradigms for lung cancer, the disease still remains a major concern worldwide. Targeting molecular pathways as Hedgehog (Hh) and Mitogen-activated protein kinase (MAPK) represent a new hope in lung cancer treatment. This work was undertaken to evaluate the antitumor effects of GANT61 (5 μM), BI-847325(30 μM), and GANT61 (5 μM)/BI-847325(30 μM) combination on A549 adenocarcinoma lung cancer cell line. The growth inhibition 50 (GI50) for both drugs was performed using MTT. The protein levels of Caspase-3, Bcl-2-associated X protein (Bax), Myeloid cell leukemia sequence 1 (MCL-1), cyclin D1, vascular endothelial growth factor (VEGF), extracellular signal-regulated kinases (ERK), p-Akt, and phosphohistone H3 (pHH3) were measured using ELISA. Glioma-associated oncogene homolog 1(Gli1) gene expression was assessed by quantitative real-time PCR. The GI50 for GANT61 and BI-8473255 were 5 µM and 30 µM, respectively. Caspase-3 and Bax protein levels were significantly elevated while MCL-1, cyclin D1, VEGF, ERK 1/2, p-Akt, and pHH3 levels were significantly reduced by both drugs and their combination relative to the control group. Gli1 gene expression was down-regulated in all groups relative to the control group. GANT61, BI-847325 and their combination inhibited proliferation and angiogenesis but activated the apoptotic pathway. Both drugs conferred a profound negative impact on the crosstalk between each of Hh and MAPK pathways and Phosphoinositide 3 -kinases (PI3K)/Akt/Mammalian target of Rapamycin (mTOR). To the best of our knowledge, the antitumor effects of BI-847325/GANT61 combination have not been tested before. Further in-vitro and in-vivo studies are warranted to support the findings.

Factors Affecting the Treatment Success of Short-Term Regimen for Drug Resistant Tuberculosis (DR TB) Patients at Dr. Saiful Anwar General Hospital Malang

Background: Epidermal growth factor (EGFR) is a transmembrane receptor that plays an important role in the development of cancer phenotypes. Some patients with lung cancer have genetic mutations. Several studies have found a close correlation of EGFR gene mutation with 15-20% of lung adenocarcinoma cases. This study aimed to determine the EGFR profile in adenocarcinoma lung cancer patients at Haji Adam Malik General Hospital.Methods: This was a prospective cohort study conducted at Haji Adam Malik General Hospital, Medan. This study used patients data for 3 years, starting from January 1, 2014 to D1ecember 31, 2016. The sample size in this study was 34 patients. The data were then analyzed using SPSS.Results: All patients were adenocarcinoma lung cancer patients with positive EGFR mutation. There were 9 subjects with EGFR mutation in exon 19; 11 subjects with exon 21 L858R mutation; and 3 subjects with exon 21 L861Q mutation. Meanwhile, there were 3 subjects with uncommon EGFR mutations, namely exon 18 mutation. Majority of subjects with exon 19 mutation were male, aged &gt;60 years, smokers with mixed types of cigarettes and severe brinkmann index. In subjects with exon 21 L858R mutation, most of the patients were male, aged 50-60 years, smokers with mixed cigarette types and severe brinkmann index. The same characteristics were also observed in subjects with exon 18 mutation. However, for exon 21 L861Q mutation, the majority of subjects were female with varying ages, and were not smokers. Conclusion: Most of the study subjects profiles were male, aged over 60 years, smokers, with mixed types of cigarettes, and with severe Brinkman Index. The EGFR mutations most commonly occured in exon 21, followed by exon 19 (ins/del exon 19), exon 18, and a combination of 2 exons.

Photocatalytic Activity of Orchid-Flower-Shaped ZnO Nanoparticles, toward Cationic and Anionic Dye Degradation under Visible Light, and Its Anti-Cancer Potential

Orchid-flower-shaped ZnO nanomaterials were successfully synthesized via green synthesis and an eco-friendly approach using an aqueous extract of Lycium chinense fruit as a reducing and capping agent. The synthesized Lycium chinense orchid-flower-shaped ZnO (LC-ZnO/OF) nanoparticles (NPs) were characterized using different analytical methods through X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), photoelectron spectroscopy (XPS), and photoluminescence (PL). The FE-TEM analysis revealed the orchid flower shape of the nanoparticles, and the elemental composition was confirmed via XPS analysis. The photocatalytic activity of the nanoparticles was determined by the degrading cationic dye methylene blue (MB) and the anionic dye Eosin Y (EY) under visible light irradiation at (400 w) within 180 min time, where it showed a significant ability to degrade both cationic and anionic dye by almost 50%. The LC-ZnO/OF photocatalyst was also used to check the toxicity level in human cancer cells, where it exhibited remarkable cytotoxicity to the human lung cancer (A549 cell line) and human gastric adenocarcinoma hyperdiploid (AGS cell line). The present investigation suggests that LC-ZnO/OF has the potential photocatalytic ability to degrade toxic dye as well as have anti-cancer effects. These preliminary results suggest that LC-ZnO/OF could have a significant impact on the environmental and biomedical fields.

O12-1 Ramucirumab-containing chemotherapy for gastrointestinal neuroendocrine carcinoma: RAM-NEC study (WJOG13420G)

Second-line chemotherapy (CTx) for advanced gastrointestinal neuroendocrine carcinoma (GI-NEC) after platinum-based CTx is adopted according to the guidelines of GI adenocarcinoma or small cell lung cancer in daily practice. Recently, some reports suggested that vascular endothelial growth factor receptor-2 highly expressed in tumor vessels of GI-NEC. In this study, we evaluated the efficacy of ramucirumab (RAM)-containing CTx.

Prognostic factors in curative intent stage I lung adenocarcinoma: a retrospective hospital-based cohort study

Radiotherapy or surgery, depending on hospital specialisation status (ie, High Complexity Centres in Oncology [HCCO; hospitals with infrastructure, technology, physical facilities, equipment, and human resources suitable for highly complex specialised assistance], or Partial Hospital Complexity Centres in Oncology [PHCCO; hospitals with infrastructures and specialisation similar to that of HCCOs, but doing diagnosis and treatment for common cancers only], as per nomenclature used in Brazil), can increase overall survival in patients diagnosed with lung adenocarcinoma. However, many patients do not accept surgery because of comorbidities and personal preferences. In addition, the long time between diagnosis and treatment and the qualification of the hospital specialisation status might affect the outcomes for patients with lung adenocarcinoma. The aim of this study was to evaluate prognostic factors of overall survival in patients with stage I lung cancer adenocarcinoma diagnosed in the state of São Paulo, Brazil. This was a retrospective hospital-based cohort study including patients of both sexes, aged 18 years or older, diagnosed with stage IA or IB lung adenocarcinoma and undergoing radiotherapy or surgery between Jan 1, 2000, and Dec 31, 2015, in 75 hospitals in the state of São Paulo, Brazil. The variables analysed were sex, age, education level, health system (public or private), clinical stage at diagnosis, time of diagnosis (2000-05; 2006-10; or 2011-15), type of treatment, time between first contact with health-care services and diagnosis (up to 1 month; 1-2 months; or 2 or more months), time between diagnosis and start of treatment (up to 1 month; 1-2 months; or 2 or more months), and hospital specialisation status (HCCO or PHCCO). Multivariate Cox regression analysis was applied to assess the risk of death. The second model was elaborated using propensity score technique. Balancing variables were sex, age group, type of treatment (radiotherapy or surgery), and educational attainment (including individuals who did not attend school), considering hospital specialisation status as dependent variable. The matching was done by logistic regression with the k-nearest neighbour algorithm. 681 patients were included. The 5-year overall survival rate was 58·1% (95% CI 53·9-62·1%). In the conventional multiple Cox regression analysis, patients who underwent radiotherapy alone had a risk of death nearly three times higher than that of patients who underwent surgery only (hazard ratio [HR] 3·44 [95% CI 2·45-4·82]; p<0·0001). Patients treated in PHCCOs had a higher risk of death (HR 1·49 [95% CI 1·10-2·03]; p=0·01) than patients treated in HCCOs. Patients aged 60 years or older and male patients also had a higher risk of death than patients younger than 60 years (HR 1·36 [95% CI 1·00-1·85]; p=0·048) and female patients (1·52 [1·17-1·98]; p=0·002), respectively. The multivariate regression analysis using propensity score technique showed that patients treated in HCCO hospitals had a higher risk of death (HR 1·80 [95% CI 1·26-2·56]), as did patients for whom time between diagnosis and start of treatment was longer than 2 months (2·00 [1·33-3·00]). Patients diagnosed in 2011-15 had a lower the risk of death than patients diagnosed in 2000-05 (HR 0·60 [95% CI 0·38-0·94]; p=0·027; protective factor). Our results show that the most significant prognostication factors for risk of death in patients with lung adenocarcinoma were delay between diagnosis and start of treatment and treatment in PHCCO hospitals. Patients diagnosed after 2010 also had a lower risk of death than those diagnosed before 2010. Incorporation of better patient care techniques, staging technology, and postoperative care can potentially reduce the risk of death. Lower mortality in HCCOs is likely due to the higher availability of multidisciplinary teams, and better infrastructure and technological structure dedicated to the care of all types of cancers. Oncocentro Foundation and Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.

Based on the Development and Verification of a Risk Stratification Nomogram: Predicting the Risk of Lung Cancer-Specific Mortality in Stage IIIA-N2 Unresectable Large Cell Lung Neuroendocrine Cancer Compared With Lung Squamous Cell Cancer and Lung Adenocarcinoma.

BackgroundThe purpose of this study is to predict overall survival (OS) and lung cancer-specific survival (LCSS) in patients with stage IIIA-N2 unresectable lung squamous cell cancer (LUSC), lung adenocarcinoma (LUAD), and large cell neuroendocrine cancer (LCNEC) by constructing nomograms and to compare risk and prognostic factors affecting survival outcomes in different histological subtypes.MethodsWe included 11,505 unresectable NSCLC patients at stage IIIA-N2 between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Moreover, competition models and nomograms were developed to predict prognostic factors for OS and LCSS.ResultsAnalysis of the SEER database identified 11,505 NSCLC patients, of whom 5,559 (48.3%) have LUAD, 5,842 (50.8%) have LUSC, and 104 (0.9%) have LCNEC. Overall, both OS and LCSS were significantly better in stage IIIA-N2 unresectable LUAD than in LCNEC, while there was no statistically significant difference between LUSC and LCNEC. Age, gender, T stage, chemotherapy, and radiotherapy were significantly associated with OS rates in LUAD and LUSC. However, chemotherapy was the only independent factor for LCNEC (p < 0.01).From competitive risk models, we found that older age, larger tumors, non-chemotherapy and non-radiotherapy were associated with a increased risk of death from LUAD and LUSC. Unlike prognostic factors for OS, our study showed that both chemotherapy and radiotherapy were all LCNEC-specific survival factors for both LCSS and non-LCSS LCNEC.ConclusionOur study reports that unresectable patients with stage IIIA-N2 LCNEC and LUSC have worse LCSS than LUAD. The study’s first prognostic nomogram constructed for patients with unresectable stage IIIA-N2 NSCLC can accurately predict the survival of different histological types, which may provide a practical tool to help clinicians assess prognosis and stratify these prognostic risks to determine which patients should be given an optimized individual treatment strategy based on histology.

Ubenimex Combined with Pemetrexed Upregulates SOCS1 to Inhibit Lung Adenocarcinoma Progression via the JAK2-STAT3 Signaling Pathway.

To study the effects of ubenimex (UBE) combined with pemetrexed (PEM) on lung adenocarcinoma cell behavior and its molecular mechanism, the tissue samples from lung adenocarcinoma patients who received PEM chemotherapy, those with PEM combined with UBE chemotherapy, and healthy volunteers were retrieved and analyzed. The expression levels of the suppressor of cytokine signaling 1 (SOCS1) in the human lung adenocarcinoma cancer cell lines A549 and PC-9 and tissues were detected by qRT-PCR. MTT assay was performed for cell proliferation. Cell apoptosis was detected by flow cytometry. Cell invasion ability was assessed using the Transwell assay. The expression levels of the JAK2/STAT3 signaling pathway proteins and apoptosis-related proteins were detected by Western blot. The antitumor effect of PEM combined with UBE was tested in nude mice using the tumor formation assay. Our results showed that UBE treatment, alone or combined with PEM, inhibited lung adenocarcinoma cell migration, invasion, and proliferation; promoted apoptosis; significantly increased the G0/G1-phase cell ratio; reduced the S-phase cell ratio; and inhibited the in vivo growth of tumor cells. UBE alone or in combination with PEM also inhibited the JAK2/STAT3 signaling pathway in lung adenocarcinoma cells. In addition, UBE combined with PEM therapy was associated with increased SOCS1 expression in patients' serum and knocking down SOCS1 reversed the antitumor effects of UBE and PEM. Overall, combination therapy with UBE and PEM could inhibit the JAK2-STAT3 signaling pathway by upregulating SOCS1 expression to hinder the progression of lung adenocarcinoma cells.