Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Qi X

PROVIDER: S-EPMC7658512 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

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

Qi Xiaoguang X Qi Chunyan C Wu Tao T Hu Yi Y

Technology in cancer research & treatment 20200101

<h4>Objective</h4>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.<h4>Methods</h4>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 Ontolo ...[more]

PMID: 33153411

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Project description:ImportanceOnly a small fraction of patients with advanced non-small cell lung cancer (NSCLC) respond to immune checkpoint inhibitor (ICI) treatment. For optimal personalized NSCLC care, it is imperative to identify patients who are most likely to benefit from immunotherapy.ObjectiveTo develop a supervised deep learning-based ICI response prediction method; evaluate its performance alongside other known predictive biomarkers; and assess its association with clinical outcomes in patients with advanced NSCLC.Design, setting, and participantsThis multicenter cohort study developed and independently validated a deep learning-based response stratification model for predicting ICI treatment outcome in patients with advanced NSCLC from whole slide hematoxylin and eosin-stained images. Images for model development and validation were obtained from 1 participating center in the US and 3 in the European Union (EU) from August 2014 to December 2022. Data analyses were performed from September 2022 to May 2024.ExposureMonotherapy with ICIs.Main outcomes and measuresModel performance measured by clinical end points and objective response rate (ORR) differentiation power vs other predictive biomarkers, ie, programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), and tumor-infiltrating lymphocytes (TILs).ResultsA total of 295 581 image tiles from 958 patients (mean [SD] age, 66.0 [10.6] years; 456 [48%] females and 502 [52%] males) treated with ICI for NSCLC were included in the analysis. The US-based development cohort consisted of 614 patients with median (IQR) follow-up time of 54.5 (38.2-68.1) months, and the EU-based validation cohort, 344 patients with 43.3 (27.4-53.9) months of follow-up. The ORR to ICI was 26% in the developmental cohort and 28% in the validation cohort. The deep learning model's area under the receiver operating characteristic curve (AUC) for ORR was 0.75 (95% CI, 0.64-0.85) in the internal test set and 0.66 (95% CI, 0.60-0.72) in the validation cohort. In a multivariable analysis, the deep learning model's score was an independent predictor of ICI response in the validation cohort for both progression-free (hazard ratio, 0.56; 95% CI, 0.42-0.76; P < .001) and overall survival (hazard ratio, 0.53; 95% CI, 0.39-0.73; P < .001). The tuned deep learning model achieved a higher AUC than TMB, TILs, and PD-L1 in the internal set; in the validation cohort, it was superior to TILs and comparable with PD-L1 (AUC, 0.67; 95% CI, 0.60-0.74), with a 10-percentage point improvement in specificity. In the validation cohort, combining the deep learning model with PD-L1 scores achieved an AUC of 0.70 (95% CI, 0.63-0.76), outperforming either marker alone, with a response rate of 51% compared to 41% for PD-L1 (≥50%) alone.Conclusions and relevanceThe findings of this cohort study demonstrate a strong and independent deep learning-based feature associated with ICI response in patients with NSCLC across various cohorts. Clinical use of this deep learning model could refine treatment precision and better identify patients who are likely to benefit from ICI for treatment of advanced NSCLC.

Project description:BackgroundAdvanced non-small cell lung cancer (NSCLC) presents significant treatment challenges, with chemo-immunotherapy emerging as a promising approach. This study explores the potential of lipidomic biomarkers to predict responses to chemo-immunotherapy in advanced non-small cell lung cancer (NSCLC) patients.MethodsA prospective analysis was conducted on 68 NSCLC patients undergoing chemo-immunotherapy, divided into disease control (DC) and progressive disease (PD) groups based on treatment response. Pre-treatment serum samples were subjected to lipidomic profiling using liquid chromatography-mass spectrometry (LC-MS). Key predictive lipids (biomarkers) were identified through projection to latent structures discriminant analysis. A biomarker combined model and a clinical combined model were developed to enhance the prediction accuracy. The predictive performances of the clinical combined model in different histological subtypes were also performed.ResultsSix lipids were identified as the key lipids. The expression levels of PC(16:0/18:2), PC(16:0/18:1), PC(16:0/18:0), CE(20:1), and PC(14:0/18:1) were significantly up-regulated. While the expression level of TAG56:7-FA18:2 was significantly down-regulated. The biomarker combined model demonstrated a receiver operating characteristic (ROC) curve of 0.85 (95% CI: 0.75-0.95) in differentiating the PD from the DC. The clinical combined model exhibited an AUC of 0.87 (95% CI: 0.79-0.96) in differentiating the PD from the DC. The clinical combined model demonstrated good discriminability in DC and PD patients in different histological subtypes with the AUC of 0.78 (95% CI: 0.62-0.96), 0.79 (95% CI: 0.64-0.94), and 0.86 (95% CI: 0.52-1.00) in squamous cell carcinoma, large cell carcinoma, and adenocarcinoma subtype, respectively. Pathway analysis revealed the metabolisms of linoleic acid, alpha-linolenic acid, glycerolipid, arachidonic acid, glycerophospholipid, and steroid were implicated in the chemo-immunotherapy response in advanced NSCLC.ConclusionLipidomic profiling presents a highly accurate method for predicting responses to chemo-immunotherapy in patients with advanced NSCLC, offering a potential avenue for personalized treatment strategies.

Project description:Background: Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC. Methods: The microarray datasets of GSE18842, GSE30219, GSE31210, GSE32863 and GSE40791 from Gene Expression Omnibus database were downloaded. The differential expressed genes (DEGs) between NSCLC and normal samples were identified by limma package. The construction of protein-protein interaction (PPI) network, module analysis and enrichment analysis were performed using bioinformatics tools. The expression and prognostic values of hub genes were validated by GEPIA database and real-time quantitative PCR. Based on these DEGs, the candidate small molecules for NSCLC were identified by the CMap database. Results: A total of 408 overlapping DEGs including 109 up-regulated and 296 down-regulated genes were identified; 300 nodes and 1283 interactions were obtained from the PPI network. The most significant biological process and pathway enrichment of DEGs were response to wounding and cell adhesion molecules, respectively. Six DEGs (PTTG1, TYMS, ECT2, COL1A1, SPP1 and CDCA5) which significantly up-regulated in NSCLC tissues, were selected as hub genes according to the results of module analysis. The GEPIA database further confirmed that patients with higher expression levels of these hub genes experienced a shorter overall survival. Additionally, CMap predicted the 20 most significant small molecules as potential therapeutic drugs for NSCLC. DL-thiorphan was the most promising small molecule to reverse the NSCLC gene expression. Conclusions: Based on the gene expression profiles of 696 NSCLC samples and 237 normal samples, we first revealed that PTTG1, TYMS, ECT2, COL1A1, SPP1 and CDCA5 could act as the promising novel diagnostic and therapeutic targets for NSCLC. Our work will contribute to clarifying the molecular mechanisms of NSCLC initiation and progression.

Project description:ObjectivesIn radiomics, high-throughput algorithms extract objective quantitative features from medical images. In this study, we evaluated CT-based radiomics features, clinical features, in-depth learning features, and a combination of features for predicting a good pathological response (GPR) in non-small cell lung cancer (NSCLC) patients receiving immunotherapy-based neoadjuvant therapy (NAT).Materials and methodsWe reviewed 62 patients with NSCLC who received surgery after immunotherapy-based NAT and collected clinicopathological data and CT images before and after immunotherapy-based NAT. A series of image preprocessing was carried out on CT scanning images: tumor segmentation, conventional radiomics feature extraction, deep learning feature extraction, and normalization. Spearman correlation coefficient, principal component analysis (PCA), and least absolute shrinkage and selection operator (LASSO) were used to screen features. The pretreatment traditional radiomics combined with clinical characteristics (before_rad_cil) model and pretreatment deep learning characteristics (before_dl) model were constructed according to the data collected before treatment. The data collected after NAT created the after_rad_cil model and after_dl model. The entire model was jointly constructed by all clinical features, conventional radiomics features, and deep learning features before and after neoadjuvant treatment. Finally, according to the data obtained before and after treatment, the before_nomogram and after_nomogram were constructed.ResultsIn the before_rad_cil model, four traditional radiomics features ("original_shape_flatness," "wavelet hhl_firer_skewness," "wavelet hlh_firer_skewness," and "wavelet lll_glcm_correlation") and two clinical features ("gender" and "N stage") were screened out to predict a GPR. The average prediction accuracy (ACC) after modeling with k-nearest neighbor (KNN) was 0.707. In the after_rad_cil model, nine features predictive of GPR were obtained after feature screening, among which seven were traditional radiomics features: "exponential_firer_skewness," "exponential_glrlm_runentropy," "log- sigma-5-0-mm-3d_firer_kurtosis," "logarithm_skewness," "original_shape_elongation," "original_shape_brilliance," and "wavelet llh_glcm_clustershade"; two were clinical features: "after_CRP" and "after lymphocyte percentage." The ACC after modeling with support vector machine (SVM) was 0.682. The before_dl model and after_dl model were modeled by SVM, and the ACC was 0.629 and 0.603, respectively. After feature screening, the entire model was constructed by multilayer perceptron (MLP), and the ACC of the GPR was the highest, 0.805. The calibration curve showed that the predictions of the GPR by the before_nomogram and after_nomogram were in consensus with the actual GPR.ConclusionCT-based radiomics has a good predictive ability for a GPR in NSCLC patients receiving immunotherapy-based NAT. Among the radiomics features combined with the clinicopathological information model, deep learning feature model, and the entire model, the entire model had the highest prediction accuracy.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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