CD200 and CD200R1 are differentially expressed and have differential prognostic roles in non-small cell lung cancer

Yoshimura, Katsuhiro; Suzuki, Yuzo; Inoue, Yusuke; Tsuchiya, Kazuo; Karayama, Masato; Iwashita, Yuji; Kahyo, Tomoaki; Kawase, Akikazu; Tanahashi, Masayuki; Inui, Naoki; Funai, Kazuhito; Shinmura, Kazuya; Niwa, Hiroshi; Sugimura, Haruhiko; Suda, Takafumi

doi:10.1080/2162402x.2020.1746554

Cited by 21 publications

(20 citation statements)

References 57 publications

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“…Recently, Yoshimura et al explored the clinicopathologic and prognostic implications of the CD200/CD200R immune checkpoint in 632 NSCLC patients by immunohistochemistry (IHC) [ 22 ]. In this study, CD200 expression was rarely seen in the stroma, with 93.3% of cases showing absence of stromal CD200 staining.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer

Vathiotis

MacNeil

Zugazagoitia

et al. 2021

Cancers

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CD200/CD200R is an immune checkpoint with broad expression patterns and a potential target for immune therapy. In this study, we assess both CD200 and CD200R expression in solid tumors, with a focus on lung cancer, and evaluate their association with clinicopathologic characteristics, mutation status, outcome, and programmed death-ligand 1 (PD-L1) expression. We used multiplexed quantitative immunofluorescence (QIF) to measure the expression of CD200 and CD200R in a total of 455 patients from three lung cancer cohorts. Using carefully validated antibodies, we performed target measurement with tyramide-based QIF panels and analyzed the data using the PM2000 microscope and AQUA software. CD200 tumor positivity was found in 29.7% of non-small cell lung cancer (NSCLC) patients and 33.3% of lung large cell neuroendocrine carcinoma (LCNEC) patients. CD200 demonstrated notable intratumoral heterogeneity. CD200R was expressed in immune cells in 25% of NSCLC and 41.3% of LCNEC patients. While CD200R is predominantly expressed in immune cells, rare tumor cell staining was seen in a highly heterogeneous pattern. CD200R expression in the stromal compartment was significantly higher in patients with squamous differentiation (p < 0.0001). Neither CD200 nor CD200R were associated with other clinicopathologic characteristics or mutation status. Both biomarkers were not prognostic for disease-free or overall survival in NSCLC. CD200 showed moderate correlation with PD-L1. CD200/CD200R pathway is frequently expressed in lung cancer patients. Differential expression patterns of CD200 and CD200R with PD-L1 suggest a potential role for targeting this pathway alone in patients with NSCLC.

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Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer

Vathiotis

MacNeil

Zugazagoitia

et al. 2021

Cancers

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“…Specifically, the decrease of immune activity would increase the chance of cancer and chronic infection, and the main cause of pathological evolution of various acute infectious diseases, allergic reactions and autoimmune diseases was the over-active immune system ( Roth et al, 2020 ; Yoshimura et al, 2020 ). Considering the interaction between various innate immune and adaptive immune, the environment of cytokines and chemokines secreted by immune cells was extremely important for the fate of these cells, which played a role of isolation or mutual adjustment ( Yoshimura et al, 2020 ). Practical experiments had proved the expression level of IL-35 in serum in patients with PBC were low ( Li et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

The Role of IL-35 in the Pathophysiological Processes of Liver Disease

Lian

et al. 2021

Front. Pharmacol.

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It is known that liver diseases have several characteristics of massive lipid accumulation and lipid metabolic disorder, and are divided into liver inflammation, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients. Interleukin (IL)-35, a new-discovered cytokine, can protect the liver from the environmental attack by increasing the ratio of Tregs (T regulatory cells) which can increase the anti-inflammatory cytokines and inhibit the proliferation of immune cellular. Interestingly, two opposite mechanisms (pro-inflammatory and anti-inflammatory) have connection with the ultimate formation of liver diseases, which suggest that IL-35 may play crucial function in the process of liver diseases through immunosuppressive regulation. Besides, some obvious advantages also imply that IL-35 can be considered as a new therapeutic target to control the progression of liver diseases, while its mechanism of function still needs further research.

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“…Expression signature for LUAD consists of 35 gene which 27 of are protein-coding genes while two are long intergenic non-protein coding RNA, one is antisense RNA, three are pseudogenes and two are novel transcripts. Many of the coding genes are lung cancer or other cancer types related such as ADAMTS15 [ 44 ], ASB2 [ 45 ] and EPHX1 [ 46 ] with potential tumor suppressor roles; ANGPTL4 [ 47 ], ASCL2 [ 48 ], CCL20 [ 49 ], DKK1 [ 50 ], GRIK2 [ 51 ], LDHA [ 52 ], RGS20 [ 53 ], RHOQ [ 54 ], TLE1 [ 55 ] and WBP2 [ 56 ] with potential oncogenic roles; and CD200 [ 57 ], CD200R1 [ 57 ], CCDC181 [ 58 ], GNPNAT1 [ 59 ], IRX2 [ 60 ], LDLRAD3 [ 61 ], STAP1 [ 62 ], LINC00578 [ 63 ] with prognostic potential. Moreover, MS4A1 is dysregulated in asbestos-related lung squamous carcinoma [ 64 ], RAB9B is a target of miR-15/16 which are highly related to lung cancer [ 65 ], LINC00539 is related to tumor immune response [ 66 ] while long non-coding RNA, OGFRP1, regulates non-small-cell lung cancer progression [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

Zengin

Önal-Süzek

2021

JPM

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Lung cancer is the second most frequently diagnosed cancer type and responsible for the highest number of cancer deaths worldwide. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are subtypes of non-small-cell lung cancer which has the highest frequency of lung cancer cases. We aimed to analyze genomic and transcriptomic variations including simple nucleotide variations (SNVs), copy number variations (CNVs) and differential expressed genes (DEGs) in order to find key genes and pathways for diagnostic and prognostic prediction for lung adenocarcinoma and lung squamous cell carcinoma. We performed a univariate Cox model and then lasso-regularized Cox model with leave-one-out cross-validation using The Cancer Genome Atlas (TCGA) gene expression data in tumor samples. We generated 35- and 33-gene signatures for prognostic risk prediction based on the overall survival time of the patients with LUAD and LUSC, respectively. When we clustered patients into high- and low-risk groups, the survival analysis showed highly significant results with high prediction power for both training and test datasets. Then, we characterized the differences including significant SNVs, CNVs, DEGs, active subnetworks, and the pathways. We described the results for the risk groups and cancer subtypes separately to identify specific genomic alterations between both high-risk groups and cancer subtypes. Both LUAD and LUSC high-risk groups have more downregulated immune pathways and upregulated metabolic pathways. On the other hand, low-risk groups have both up- and downregulated genes on cancer-related pathways. Both LUAD and LUSC have important gene alterations such as CDKN2A and CDKN2B deletions with different frequencies. SOX2 amplification occurs in LUSC and PSMD4 amplification in LUAD. EGFR and KRAS mutations are mutually exclusive in LUAD samples. EGFR, MGA, SMARCA4, ATM, RBM10, and KDM5C genes are mutated only in LUAD but not in LUSC. CDKN2A, PTEN, and HRAS genes are mutated only in LUSC samples. The low-risk groups of both LUAD and LUSC tend to have a higher number of SNVs, CNVs, and DEGs. The signature genes and altered genes have the potential to be used as diagnostic and prognostic biomarkers for personalized oncology.

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CD200 and CD200R1 are differentially expressed and have differential prognostic roles in non-small cell lung cancer

Cited by 21 publications

References 57 publications

Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer

Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer

The Role of IL-35 in the Pathophysiological Processes of Liver Disease

Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

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