scholarly journals Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jia-Jia Zhang ◽  
Jiang Hong ◽  
Yu-Shui Ma ◽  
Yi Shi ◽  
Dan-Dan Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Small Cell Lung Cancer ◽  
Logistic Regression Analysis ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hub Genes

Non-small-cell lung cancer (NSCLC) is one of the most devastating diseases worldwide. The study is aimed at identifying reliable prognostic biomarkers and to improve understanding of cancer initiation and progression mechanisms. RNA-Seq data were downloaded from The Cancer Genome Atlas (TCGA) database. Subsequently, comprehensive bioinformatics analysis incorporating gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the protein-protein interaction (PPI) network was conducted to identify differentially expressed genes (DEGs) closely associated with NSCLC. Eight hub genes were screened out using Molecular Complex Detection (MCODE) and cytoHubba. The prognostic and diagnostic values of the hub genes were further confirmed by survival analysis and receiver operating characteristic (ROC) curve analysis. Hub genes were validated by other datasets, such as the Oncomine, Human Protein Atlas, and cBioPortal databases. Ultimately, logistic regression analysis was conducted to evaluate the diagnostic potential of the two identified biomarkers. Screening removed 1,411 DEGs, including 1,362 upregulated and 49 downregulated genes. Pathway enrichment analysis of the DEGs examined the Ras signaling pathway, alcoholism, and other factors. Ultimately, eight prioritized genes (GNGT1, GNG4, NMU, GCG, TAC1, GAST, GCGR1, and NPSR1) were identified as hub genes. High hub gene expression was significantly associated with worse overall survival in patients with NSCLC. The ROC curves showed that these hub genes had diagnostic value. The mRNA expressions of GNGT1 and NMU were low in the Oncomine database. Their protein expressions and genetic alterations were also revealed. Finally, logistic regression analysis indicated that combining the two biomarkers substantially improved the ability to discriminate NSCLC. GNGT1 and NMU identified in the current study may empower further discovery of the molecular mechanisms underlying NSCLC’s initiation and progression.

Landmark Studies of Targeted Therapies for Advanced Non-Small Cell Lung Cancer: A Guide for Pulmonologists

2020 ◽  
Vol 16 (1) ◽  
pp. 5-10
Author(s):  
Adrien Costantini ◽  
Theodoros Katsikas ◽  
Clementine Bostantzoglou
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Standard Of Care ◽  
Genetic Alterations ◽  
Small Cell ◽  
Extensive Literature ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Mutational Status

Over the past decade, major breakthroughs in the understanding of lung cancer histology and mutational pathways have radically changed diagnosis and management. More specifically, in non-small cell lung cancer (NSCLC), tumour characterisation has shifted from differentiating based solely on histology to characterisation that includes genetic profiling and mutational status of Epidermal Growth Factor (EGFR), Anaplastic Lymphoma Kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF. These genetic alterations can be targeted by specific drugs that result in improved progression-free survival, as well as higher response rates and are currently standard of care for NSCLC patients harbouring these mutations. In this a narrative, non-systematic review we aim to handpick through the extensive literature and critically present the ground-breaking studies that lead to the institution of tailored treatment options as the standard of care for the main targetable genetic alterations.

Improvements in access to cancer clinical trials facilitated by comprehensive genomic profiling in non-small cell lung cancer.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 59-59
Author(s):  
Woojung Lee ◽  
Scott Spencer ◽  
Josh John Carlson ◽  
Tam Dinh ◽  
Victoria Dayer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Eligibility Criteria ◽  
Comprehensive Genomic Profiling

59 Background: The use of comprehensive genomic profiling (CGP) in cancer patients could lead to additional enrollment in clinical trials that study novel genetic biomarkers, potentially reducing treatment costs for payers and improving health outcomes for patients. Our objective was to estimate the number of additional clinical trials in which patients with non-small cell lung cancer (NSCLC) could potentially enroll due to the use of CGP vs. a comparator panel of 50 genes or less. Methods: Clinical trials in NSCLC that started between 2015 - 2020 were identified from the Aggregate Analysis of ClinicalTrials.gov (AACT) database. Trials with unknown status or study sites outside the United States only were excluded. We abstracted information on required genetic alterations based on the study eligibility criteria. We calculated the incremental number of trials available to patients due to results generated by CGP (FoundationOne CDx, 324 genes) vs. a commercially available comparator panel that was 50 genes or less (Oncomine Dx Target Test, 23 genes) by phase and calendar year. The additional trials were characterized by disease severity, type of therapy, and setting. Results: Enrollment eligibility was dependent on genetic variant status in 35% (250/709) of all identified NSCLC trials. There were 29 (248 vs. 219) additional clinical trials available to patients through the use of CGP, 12% of all gene-specific trials for NSCLC. We identified 45 uses of genetic markers in the 29 additional clinical trials. The most frequent genetic marker in the incremental trials was microsatellite instability, accounting for 44% of all identified markers (20/45). The incremental number of trials available to patients due to the use of CGP did not vary significantly over time but varied by phase – most of the additional clinical trials were in phase 1 or 2 (28/29, 97%). Most of the incremental trials were in metastatic disease (22/29, 76%) and were conducted in academic or advanced community settings (18/29, 62%). The most frequently studied type of intervention in these studies was targeted monotherapy (8/29, 28%), followed by immuno-monotherapy (7/29, 24%). Conclusions: Clinical trials in NSCLC initiated over the past 5 years have consistently included CGP-specific genes or markers in eligibility criteria. Patients with NSCLC have the potential to benefit from the use of CGP as compared to smaller gene panels through improved access to clinical trials.[Table: see text]

scholarly journals Association Between Triglyceride Glucose Index and Non-Small Cell Lung Cancer Risk in Chinese Population

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Yan ◽  
Yujuan Gao ◽  
Jingzhi Tong ◽  
Mi Tian ◽  
Jinghong Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Cancer Risk ◽  
Small Cell Lung Cancer ◽  
Roc Curve ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tyg Index ◽  
The Relationship

BackgroundNumerous studies showed that insulin resistance (IR) was associated with cancer risk. However, few studies investigated the relationship between IR and non-small cell lung cancer (NSCLC). The aim of this study is to explore the association of triglyceride glucose (TyG) index, a simple surrogate marker of IR, with NSCLC risk.Methods791 histologically confirmed NSCLC cases and 787 controls were enrolled in the present study. Fasting blood glucose and triglyceride were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dl) ×fasting glucose (mg/dl)/2]. Logistic regression analysis was performed to estimate the relationship between NSCLC risk and the TyG index.ResultsThe TyG index was significantly higher in patients with NSCLC than that in controls (8.42 ± 0.55 vs 8.00 ± 0.45, P < 0.01). Logistic regression analysis showed that the TyG index (OR = 3.651, 95%CI 2.461–5.417, P < 0.001) was independently associated with NSCLC risk after adjusting for conventional risk factors. In addition, a continuous rise in the incidence of NSCLC was observed along the tertiles of the TyG index (29.4 vs 53.8 vs 67.2%, P < 0.001). However, there were no differences of the TyG index in different pathological or TNM stages. In receiver operating characteristic (ROC) curve analysis, the optimal cut-off level for the TyG index to predict incident NSCLC was 8.18, and the area under the ROC curve (AUROC) was 0.713(95% CI 0.688–0.738).ConclusionsThe TyG index is significantly correlated with NSCLC risk, and it may be suitable as a predictor for NSCLC.

scholarly journals Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 245 ◽  
Author(s):  
Yosuke Miura ◽  
Noriaki Sunaga
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Future Direction ◽  
Nsclc Patients

The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations

Non–Small-Cell Lung Cancer: Real-World Cost Consequence Analysis

2021 ◽  
pp. OP.20.00863
Author(s):  
Alessandra Buja ◽  
Giulia Pasello ◽  
Giuseppe De Luca ◽  
Alberto Bortolami ◽  
Manuel Zorzi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Regression Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Average Cost ◽  
Small Cell ◽  
Tobit Regression ◽  
Small Cell Lung ◽  
Tobit Regression Analysis

PURPOSE: The present work aimed at conducting a real-world data analysis on the management costs and survival analysis comparing data from non–small-cell lung cancer (NSCLC) cases diagnosed in the Veneto region before (2015) and after (2017) the implementation of a regional diagnostic and therapeutic pathway including all new diagnostic and therapeutic strategies. METHOD: This study considered 254 incidental cases of NSCLC in 2015 and 228 in 2017 within the territory of the Padua province (Italy), as recorded by the Veneto Cancer Registry. Tobit regression analysis was performed to verify if total and each item costs (2 years after NSCLC diagnosis) are associated with index year, adjusting by year of diagnosis, sex, age, and stage at diagnosis. Logistic regression models were run to study overall mortality at 2 years, adjusting by the same covariates. RESULTS: The 2017 cohort had a lower mortality odd (odds ratio, 0.93; P = .02) and a significant increase in the average overall costs ( P = .009) than the 2015 cohort. The Tobit regression analysis by cost item showed a very significant increase in the average cost of drugs (coefficient = 5,953, P = .008) for the 2017 cohort, as well as a decrease in the average cost of hospice care (coefficient = –1,822.6, P = .022). CONCLUSION: Our study showed a survival improvement for patients with NSCLC as well as an economic burden growth. Physicians should therefore be encouraged to follow new clinical care pathways, while the steadily rising related costs underscore the need for policymakers and health professionals to pursue.

scholarly journals PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations

2016 ◽  
Vol 5 (5) ◽  
pp. e1131379 ◽  
Author(s):  
Andreas H. Scheel ◽  
Sascha Ansén ◽  
Anne M. Schultheis ◽  
Matthias Scheffler ◽  
Rieke N. Fischer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 690 ◽  
Author(s):  
Arik Bernard Schulze ◽  
Georg Evers ◽  
Andrea Kerkhoff ◽  
Michael Mohr ◽  
Christoph Schliemann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Molecular Pathways ◽  
Loss Of Function ◽  
Small Cell Lung ◽  
Therapeutic Concept ◽  
Platinum Based Chemotherapy

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkpoint inhibition yielded improved overall survival. Although there are promising molecular pathways with potential therapeutic impacts, targeted therapies are still not an integral part of routine treatment. Against this background, we evaluated current literature for potential new molecular candidates such as surface markers (e.g., DLL3, TROP-2 or CD56), apoptotic factors (e.g., BCL-2, BET), genetic alterations (e.g., CREBBP, NOTCH or PTEN) or vascular markers (e.g., VEGF, FGFR1 or CD13). Apart from these factors, the application of so-called ‘poly-(ADP)-ribose polymerases’ (PARP) inhibitors can influence tumor repair mechanisms and thus offer new perspectives for future treatment. Another promising therapeutic concept is the inhibition of ‘enhancer of zeste homolog 2’ (EZH2) in the loss of function of tumor suppressors or amplification of (proto-) oncogenes. Considering the poor prognosis of SCLC patients, new molecular pathways require further investigation to augment our therapeutic armamentarium in the future.

Identification of key microRNAs and hub genes in non‐small‐cell lung cancer using integrative bioinformatics and functional analyses

2019 ◽  
Vol 121 (3) ◽  
pp. 2690-2703 ◽  
Author(s):  
Feifeng Song ◽  
Zixue Xuan ◽  
Xiuli Yang ◽  
Xiaolan Ye ◽  
Zongfu Pan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hub Genes ◽  
Functional Analyses

Correlation between anemia before treatment with survival in patients with advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18211-18211
Author(s):  
S. R. Bella ◽  
M. E. Richardet ◽  
P. Gomez Storniolo ◽  
P. Celiz ◽  
A. Lingua ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Small Cell ◽  
Hemoglobin Level ◽  
Small Cell Lung ◽  
Cox Regression Analysis

18211 Background: Prognostic factors identified in advanced non small cell lung cancer are: age, gender, PS, h. SWOG univariable analysis in patients with chemotheraphy; confirmed these factors and show a relationship between the hemoglobin level and the overall survival; in addition the metastasic site number and cisplatin- based chemotheraphy (7). To analyse and compare the hemoglobin level before cisplatin- based chemotheraphy with survival in patients with advanced non- small cell lung cancer. Methods: Retrospective study conducted at the IONC of the 179 clinical record were analized, over a 5 year period. The collected data were: age, gender, PS, histologic type, stage, chemotheraphy cycles number, smooke history, number and metastasic site. We analyzed median and overal survival using Kaplan Meier, and the anemia as a prognostic implication factor with univariable and multivariable Cox regression analysis. Istologic type and TNM (1–6). Results: The mean age was 59 (40–79); 146 (81.5%) male and 33 (18.5%) women; histological types found were squamous cell carcinomas in 66 (37%), and adenocarcinoma in 113 (63%); stage IIIB in 61 (34%) and IV in 118 (66%). 147 (82%) were smokers and 32 (18%) were never smokers. All the patients had PS 0–1. Median overall survival time was 11.53 months and 13.88 months in the haemoglobin level < or > 11 gr/ 100 ml, respectively. (p=0.3). In univariable Cox regression analysis, smoking rates and chemotheraphy cycles number were predictors of survival (p=0.05 y p=0.018, respectively). Hemoglobine (p=0.55). In multivariable Cox regression analysis, only the number of cycles was predictor of survival (p=0.026). Hemoglobine (p=0.34). Conclusions: In our experience, a greater survival tendency was observed in patients with advanced non- small cell lung cancer who presented levels of Hemoglobine greater than 11 gr/dl, previous to cisplatin- based chemotherapy without statistical significance. [Table: see text]

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