CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer

Objective: Precision immunotherapy in non-small cell lung cancer (NSCLC) have been the focus of tumor immunity research. The aim of this study is to identify novel candidate biomarkers predicting the response to immunotherapy in NSCLC. Methods: GSE126044 was obtained from Gene Expression Omnibus (GEO). According to the response to anti-PD-1 antibody, 2 groups were divided: response group and non-response group. Differentially expressed genes (DEGs) were screened using R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. ROC curves and possible pathways of the seed genes were further analyzed. Results: In total, 588 DEGs (487 upregulated DEGs and 101 downregulated) were identified. GO and KEGG analyses showed that upregulated DEGs were mainly enriched in immune response and cell adhesion pathways, while VEGF signaling pathway and metabolic pathways were mainly enriched in downregulated DEGs. In addition, CSF1 R and HCST showed more powerful predictive ability than PDL1. More importantly, these candidate genes were not only positively correlated with the expression of PDL1 and the infiltration of CD8+ T cells in the immune microenvironment, but also might improve the prognosis in lung squamous cell carcinoma. Conclusions: CSF1 R and HCST might be novel predictive markers for immunotherapy in NSCLC.

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Co-expression Network and Prognosis Analyses of Pyroptosis-related Genes in Non-small Cell Lung Cancer

10.21203/rs.3.rs-627404/v1 ◽

2021 ◽

Author(s):

Zixiao Liu ◽

Xudong Liu ◽

Yu Zhang ◽

Yongjie Zhou ◽

Shuaibin Lian ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Hydrophobic Interactions ◽

Tumor Staging ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Differentially Expressed ◽

Small Cell Lung ◽

Nsclc Patients

Abstract Lung cancer is very difficult to diagnose in the its early stages because of its initial asymptomatic characteristics. In recent years, pyrolysis has been shown identified as a novel type of programmed cell death with inflammation mediated by the gasdermin family. In this study, 33 differentially-expressed pyroptosis-related genes were commonly identified in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. Tumor-related gasdermin family genes that were significantly differentially expressed in non-small cell lung cancer (NSCLC) tissues were identified by our co-expression network analysis. Among them, the mRNA level of GSDMB gene had significant impacts on tumor staging and survival rates of NSCLC patients. Therefore, this gene is a potential new therapeutic target for the treatment of NSCLC. In addition, the high expression levels of GSDMC/D were significantly correlated with the low overall survival (OS), progression-free survival (FP) and post-progression survival (PPS) of NSCLC patients. Therefore, this gene is a potential oncogene for NSCLC. Furthermore, four small molecules (erastin, cefotiam, metanephrine, and vorinostat) that could most significantly reverse the NSCLC gene expression were identified. They interacted with GSDMB proteins mainly through H-bonds and hydrophobic interactions. This study provides new therapeutic targets and prognostic makers for NSCLC patients.

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Isolated Renal Metastasis from Primary Lung Squamous Cell Carcinoma with Synchronous Small Cell Lung Cancer

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a6924 ◽

2019 ◽

Author(s):

L. Numan ◽

O. Abughanimeh ◽

M. Younis ◽

M. Tahboub

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Renal Metastasis

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Salivary cytokine panel indicative of non-small cell lung cancer

Journal of International Medical Research ◽

10.1177/0300060518775563 ◽

2018 ◽

Vol 46 (9) ◽

pp. 3570-3582 ◽

Cited By ~ 5

Author(s):

Tomonobu Koizumi ◽

Vivek Shetty ◽

Masaki Yamaguchi

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Odds Ratio ◽

Roc Curves ◽

Small Cell ◽

Small Cell Lung ◽

Chemokine Ligand ◽

Discriminant Ability ◽

Factor C

Objective To develop a combinatorial panel of salivary cytokines that manifests the presence of non-small cell lung cancer (NSCLC) that will eventually improve prognosis by facilitating the early diagnosis and management of this common cancer. Methods We performed a case-control study comparing salivary cytokine profiles of 35 adult subjects with NSCLC with those of 35 matched, healthy nonsmokers. Multiplex bead array assays were used to quantify 27 cytokines in saliva, serum, and oral mucosal transudate samples. Logistic regression analysis was used to develop an informative cytokine panel. Receiver operating characteristic (ROC) curves were generated to evaluate the discriminant ability of the panel. Results A combinatorial 12-cytokine panel (interleukin receptor antagonist [IL1RN], IL1B, IL6, IL7, IL8, IL10, C-C motif chemokine ligand 11 [CCL11], tumor necrosis factor, C-X-C motif chemokine ligand 10 [CXCL10], C-C motif chemokine ligand 3, C-C motif chemokine ligand 4, and platelet-derived growth factor-BB) distinguished patients with NSCLC from healthy controls. Further, ROC analysis revealed that a cytokine panel comprising IL10 (odds ratio, 1.156) and CXCL10 (odds ratio, 1.000) discriminated NSCLC with a sensitivity of 60.6% and specificity of 80.8% (area under the ROC curve, 0.701). Conclusion A combinatorial panel of select salivary cytokines indicates the presence of NSCLC.

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Sites of Synchronous Distant Metastases, Prognosis, and Nomogram for Small Cell Lung Cancer Patients with Bone Metastasis: A Large Cohort Retrospective Study

Journal of Oncology ◽

10.1155/2021/9949714 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Zhiyi Fan ◽

Zhangheng Huang ◽

Yuexin Tong ◽

Zhe Zhu ◽

Xiaohui Huang ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factors ◽

Bone Metastasis ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Treatment Modality ◽

Roc Curves ◽

Small Cell ◽

Small Cell Lung

Background. Small cell lung cancer (SCLC) is often associated with metastases at the time of diagnosis, and the bone is one of the most common sites. The primary aim of this study was to investigate the site of synchronous distant metastasis to other organs in SCLC patients with bone metastasis (BM) and develop a robust predictive prognostic model. Methods. We retrospectively analyzed the data from patients diagnosed with SCLC with BM in the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox analyses were used to identify independent prognostic factors. A prognostic nomogram was constructed and evaluated by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Then, according to the sites of metastasis and treatment modality, all patients were stratified into several subgroups. The relationship among sites of metastasis, treatment modality, and overall survival was then analyzed. Results. A total of 6253 patients were included. Independent prognostic factors for SCLC with BM were age, sex, primary site, radiotherapy, chemotherapy, brain metastasis, liver metastasis, and marital status. Calibration, ROC curves, and DCA indicated the excellent performance of the prognostic nomogram. The liver is the most common organ for extraskeletal metastases, followed by the lung. Patients with only BM had the longest mean survival time (9.30 ± 0.31 months). In the subgroup analysis, chemotherapy was an independent prognostic factor for all subgroups. In contrast, radiotherapy showed a positive effect on the prognosis of patients in all subgroups except those with bone and brain metastases and those with bone, lung, and brain metastases. Conclusions. The prognostic nomogram is expected to be an accurate and personalized tool for predicting the prognosis of SCLC patients with BM. Additionally, the determination of the sites of synchronous extraskeletal metastases and the associated prognosis helps in treatment selection.

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Expression, Prognosis and Gene Regulation Network of NFAT Transcription Factors in Non-Small Cell Lung Cancer

Pathology & Oncology Research ◽

10.3389/pore.2021.529240 ◽

2021 ◽

Vol 27 ◽

Author(s):

Jin Ma ◽

Rao Du ◽

Yan Huang ◽

Wen Zhong ◽

Huan Gui ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Cell Lung Cancer ◽

Expression Patterns ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Aberrant Expression ◽

Expression Levels

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The nuclear factor of activated T cells (NFAT) family is implicated in tumorigenesis and progression in various types of cancer. However, little is known about their expression patterns, distinct prognostic values, and potential regulatory networks in NSCLC. In this study, we comprehensively analyzed the distinct expression and prognostic value of NFATs in NSCLC through various large databases, including the Oncomine, UCSC Xena Browser, UALCAN databases, Kaplan–Meier Plotter, cBioPortal, and Enrichr. In lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), NFAT1/2/4/5 mRNA expression levels were significantly decreased and NFAT3 mRNA expression level was significantly increased. The cBioPortal database analysis showed that the mRNA dysregulation was one of the single most important factors for NFAT alteration in LUAD and LUSC and that both LUAD and LUSC cases with the alterations in the mRNA expression of NFATs had significantly better overall survival (OS). High expression levels of NFAT1/2/4/5 were significantly associated with better OS in LUAD, whereas high NFAT3 expression led to a worse OS. Overexpression of NFAT1/2 predicted better OS in LUSC, whereas high NFAT5 expression led to a worse OS. The networks for NFATs and the 50 most frequently altered neighbor genes in LUAD and LUSC were also constructed. NFATs and genes significantly associated with NFAT mRNA expression in LUAD and LUSC were significantly enriched in the cGMP-dependent protein kinase and Wnt signaling pathways. These results showed that the NFAT family members displayed varying degrees of abnormal expressions, suggesting that NFATs may be therapeutic targets for patients with NSCLC. Aberrant expression of NFATs was found to be associated with OS in the patients with NSCLC; among NFATs, NFAT3/4 may be new biomarkers for the prognosis of LUAD. However, further studies are required to validate our findings.

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PLEK2 and SCN7A: novel biomarkers of non-small cell lung cancer

10.21203/rs.3.rs-16005/v1 ◽

2020 ◽

Author(s):

Yongchang Liu ◽

Xi Li ◽

Ruimin Chang ◽

Yufan Chen ◽

Yang Gao

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Cell Adhesion ◽

Small Cell Lung Cancer ◽

Focal Adhesion ◽

Cell Lung Cancer ◽

Gene Expression Omnibus ◽

Small Cell ◽

Small Cell Lung ◽

Kaplan Meier

Abstract Objective Lung cancer is the leading cause of cancer-related death globally, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. However, the diagnosis and prognosis of NSCLC remain dim. Our team has focused on identifying differentially expressed genes (DEGs) between NSCLC tissues and adjacent tissues, which may be useful as effective diagnostic markers that can better explain the progression of NSCLC. Methods The Gene Expression Omnibus (GEO) database was used to screen the Gene Expression Omnibus series, which records the information of a large number of patients with primary NSCLC (n > 50). Then, the DEGs were validated using Student’s t -test. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID. The prognosis information was analyzed separately using data obtained from three databases, Human Protein Atlas, Kaplan–Meier Plotter, and SurvExpress. Results A series of 180 DEGs (33 upregulated and 147 downregulated genes), mainly involving genes associated with extracellular exosomes, focal adhesion, and cell adhesion, were identified via GO analysis. Subsequently, KEGG analysis demonstrated that focal adhesion, cell adhesion molecules, and PPAR signaling pathway were the most enriched pathways. Then, we paid particular attention to pleckstrin 2 (PLEK2) and sodium voltage-gated channel alpha subunit 7 (SCN7A), as they have not been investigated as cancer-related genes previously. Kaplan–Meier survival analysis illustrated that PLEK2 and SCN7A levels were significantly correlated with the prognosis of NSCLC. Conclusions Our research found that, as potential biomarkers, both PLEK2 and SCN7A are related to the development and prognosis of NSCLC. They may be used in disease screening and prognosis. The clinical significance of these two genes deserves further investigation.

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The Pharmacogenomics “Side-effect” of TP53/EGFR in Non-small Cell Lung Cancer Accompanied with Atorvastatin Therapy: A Functional Network Analysis

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190712203217 ◽

2020 ◽

Vol 19 (17) ◽

pp. 2060-2071

Author(s):

Lei Zhang ◽

Yifang Huang ◽

Xuedong Gan ◽

Siying He ◽

Xiaohuan Cheng ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Kegg Pathway ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Atorvastatin Therapy ◽

Drugbank Database

Background: Atorvastatin belongs to the group of statins and is the leading drug for hypercholesterolemia treatment. Although, its anticancer effects are highly appreciated, its properties are still unclear. The aim of this study was to explore the underlying anticancer mechanisms induced by atorvastatin and enlarge the potential target in non-small cell lung cancer. Methods: arget genes of atorvastatin were collected by the DrugBank database. Prediction of interaction between primary targets and secondary targets was performed, and protein-protein interaction network was constructed though the STRING. Then, KEGG pathway enrichment analysis was performed with WebGestalt and ClueGO, including the pathways in non-small cell lung cancer. Furthermore, a genomic alteration analysis of the selected seed genes of atorvastatin benefit and non-small cell lung cancer pathway was conducted by cBioPortal. Finally, a survival analysis with the selected seed genes in lung cancer (lung adenocarcinoma, lung squamous cell carcinoma) was conducted using Kaplan-Meier (KM) plotter. Results: To identify seed genes, 65 potential candidate genes were screened as targets for atorvastatin using STRING with DrugBank database, while the KEGG pathway was enriched to get the overlap match of pathways in non-small cell lung cancer. Then 4 seed genes, Epidermal Growth Factor Receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), AKT serine/threonine kinase 1 (AKT1) and tumor protein p53 (TP53), were selected and their genomic alternation were evaluated by cBioPortal. Survival analysis found that TP53 and EGFR showed a significant correlation (log rank P = 3e-07 and 0.023) with lung adenocarcinoma and lung squamous cell carcinoma, according to the KM analysis. Conclusion: Gene-phenotype connectivity for atorvastatin in non-small cell lung cancer was identified using functional/activity network analysis method, and our findings demonstrated that TP53 and EGFR could be the potential targets in cancer patients with atorvastatin therapy.

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Clinical and genomic features of high tumor mutation burden in patients with non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21023 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21023-e21023

Author(s):

Yuan Qiu ◽

Haihong Yang ◽

Hanzhang Chen ◽

Qiuhua Deng ◽

Liping Liu ◽

...

Keyword(s):

Lung Cancer ◽

Lymph Node ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Linear Regression Analysis ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Mutation Status ◽

Pathological Subtype

e21023 Background: TMB is associated with mono-immunotherapy efficacy for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). For early-stage NSCLC or EGFR mutated non-resectable NSCLC, TMB-H predicted better prognosis or poor response to TKIs. This research might develop potential predictive parameters for distinguishing NSCLC with high or low TMB. Methods: Samples of surgically resected, cancer tissues were collected from 499 patients with NSCLC: 29 (5.8%) lung squamous cell carcinoma (LUSC) and 468 (94.2%) lung adenocarcinoma (LUAD). The mutations and TMB were confirmed by target region capture sequencing (Oseq™-508). Results: According to the median value (3.08), TMB is divided into high (N = 244) and low (N = 255). Interactions between TMB and sex, age, location, histology, pathological subtype, lymph node, parabronchial lymph node, LVI, neuro-invasive, stage and mutation status were evaluated. The distribution of TMB-H was significantly (p < 0.001) correlated with sex, age, histology, pathological subtype, stage (TN stage) and partial mutations. Among all mutations, 6 genes (TP53 / FAT3 / KMT2D / TSHZ3 / NAV3 / EPHA3) were confirmed to be significantly related to TMB-H in NSCLC. We also found that TMB-H was significantly affected by mutation status of KRAS gene (P. G12X, p < 0.001) and missense mutations in FAT3 (p < 0.001). The Kruskal–Wallis H test results showed that the mutation types of FAT3, KRAS, TP53 and PIK3CA were closely related to TMB-H. Lasso linear regression analysis was applied and resulted the better predictors of TMB status including TSHZ3, KMT2D, TP53, gender and T stage. Conclusions: Instead of comprehensive genomic profiling to evaluate TMB, clinical characteristics and special mutation types may help to effectively screen and predicate patients with TMB-H status. [Table: see text]

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