<i>PD-L1</i> (<i>CD274</i>) promoter methylation predicts survival in colorectal cancer patients

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Dietrich, Dimo

doi:10.1080/2162402x.2016.1257454

Cited by 72 publications

(71 citation statements)

References 17 publications

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“…On the other hand, PD‐L1 is generally produced by cancer cells to escape immune surveillance, and is a molecular target for cancer immune therapy . Previous report showed that the PD‐L1 gene promoter is regulated by DNA methylation or Sp1 binding in cancer cells . There is the possibility that ATF7IP/MCAF1 may control PD‐L1 expression via Sp1,as indicated by published ChIP‐seq data of colon cancer (Figure A).…”

Section: Resultsmentioning

confidence: 89%

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Computational analysis of morphological and molecular features in gastric cancer tissues

et al. 2020

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Biological morphologies of cells and tissues represent their physiological and pathological conditions. The importance of quantitative assessment of morphological information has been highly recognized in clinical diagnosis and therapeutic strategies. In this study, we used a supervised machine learning algorithm wndchrm to classify hematoxylin and eosin (H&E)‐stained images of human gastric cancer tissues. This analysis distinguished between noncancer and cancer tissues with different histological grades. We then classified the H&E‐stained images by expression levels of cancer‐associated nuclear ATF7IP/MCAF1 and membranous PD‐L1 proteins using immunohistochemistry of serial sections. Interestingly, classes with low and high expressions of each protein exhibited significant morphological dissimilarity in H&E images. These results indicated that morphological features in cancer tissues are correlated with expression of specific cancer‐associated proteins, suggesting the usefulness of biomolecular‐based morphological classification.

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Section: Resultsmentioning

confidence: 89%

“…[41][42][43] Previous report showed that the PD-L1gene promoter is regulated by DNA methylation or Sp1 binding in cancer cells. 44,45 There is the possibility that ATF7IP/MCAF1 may control PD-L1 expression via Sp1,as indicated by published ChIP-seq data of colon cancer ( Figure S3A).…”

Section: Expression Levels Of Nuclear Atf7ip/ Mcaf1 Are Correlated mentioning

confidence: 99%

Computational analysis of morphological and molecular features in gastric cancer tissues

et al. 2020

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“…Shown is chromosome 12, position 6 771 404-6 779 853, including the LAG3 gene, its transcripts and regulatory elements (promoter, promoter flank, and CCCTCbinding factor (CTCF) binding site), and the investigated loci. The LAG3 methylation target sites of the HumanMethylation450 BeadChip beads (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and qMSP assays (4 and 8) are based on Genome Reference Consortium Human Build 38 patch release 13 (GRCh38.p13). The illustration (modified) was exported from www.ensemble.org (release 98).…”

Section: Introductionmentioning

confidence: 99%

LAG3(LAG-3,CD223) DNA methylation correlates with LAG3 expression by tumor and immune cells, immune cell infiltration, and overall survival in clear cell renal cell carcinoma

Klümper

Ralser

Bawden

et al. 2020

J Immunother Cancer

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BackgroundLymphocyte activating 3 (LAG3, LAG-3, CD223) is a promising target for immune checkpoint inhibition in clear cell renal cell carcinoma (KIRC). The aim of this study was to investigate the epigenetic regulation ofLAG3in KIRC by methylation.MethodsWe correlated quantitativeLAG3methylation levels with transcriptional activity, immune cell infiltration, and overall survival in a cohort of n=533 patients with KIRC and n=160 normal adjacent tissue (NAT) samples obtained from The Cancer Genome Atlas (TCGA). Furthermore, we analyzedLAG3methylation in peripheral blood mononuclear cells (PBMCs) and KIRC cell lines. We validated correlations between LAG3 expression, immune cell infiltrates, survival, and methylation in an independent KIRC cohort (University Hospital Bonn (UHB) cohort, n=118) by means of immunohistochemistry and quantitative methylation-specific PCR.ResultsWe found differential methylation profiles among PBMCs, NAT, KIRC cell lines, and KIRC tumor tissue. Methylation strongly correlated with LAG3 mRNA expression in KIRCs (TCGA cohort) and KIRC cell lines. In the UHB cohort, methylation correlated with LAG3-positive immune cells and tumor-intrinsic LAG3 protein expression. Furthermore,LAG3methylation strongly correlated with signatures of distinct immune cell infiltrates, an interferon-y signature (TCGA cohort), and immunohistochemically quantified CD45+, CD8+, and CD4+immune cell infiltrates (UHB cohort). LAG3 mRNA expression (TCGA cohort), methylation (both cohorts), and tumor cell-intrinsic protein expression (UHB cohort) was significantly associated with overall survival.ConclusionOur data suggest an epigenetic regulation of LAG3 expression in tumor and immune cells via DNA methylation. LAG3 expression and methylation is associated with a subset of KIRCs showing a distinct clinical course and immunogenicity. Our study provides rationale for further testingLAG3DNA methylation as a predictive biomarker for response to LAG3 immune checkpoint inhibitors.

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“…The current study demonstrated that PD-L1 methylation is positively correlated with PD-L1 protein expression, indicating that PD-L1 expression may be regulated by promoter methylation in gastric cancer. Previous research has reported that PD-L1 methylation is inversely correlated with PD-L1 mRNA expression (31). Perhaps, PD-L1 methylation regulates protein expression at the mRNA level.…”

Section: Chemotherapy Effective Disease Control ---------------------mentioning

confidence: 93%

“…It has previously been demonstrated that methylation of the PD-L1 promoter may influence prognosis in numerous cancer types. For example, increased methylation of PD-L1 was significantly associated with shorter recurrence-free survival and OS times in patients with colorectal cancer (31). Similarly, in prostate cancer, high levels of PD-L1 methylation correlated with an increased risk of recurrence (28).…”

Section: Pd-l1 Promoter Methylationmentioning

confidence: 98%

PD‑L1 gene promoter methylation represents a potential diagnostic marker in advanced gastric cancer

Xing

Cao

et al. 2019

Oncol Lett

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Gastric cancer is one of the most prevalent malignant tumors worldwide. Immunological checkpoint inhibitors of the programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling pathway are effective in the treatment of various malignant tumor types, but the potential of such immunotherapeutic techniques for the treatment of gastric cancer is yet to be elucidated. The purpose of the present study was to investigate the methylation of the PD-L1 gene promoter and its clinical significance in advanced gastric cancer, as this may suggest the use of PD-L1 promoter methylation as a novel biomarker for gastric cancer progression. In a total of 70 samples, the methylation rate of the PD-L1 gene promoter region was significantly higher in gastric cancer tissues compared with adjacent tissues. A high level of PD-L1 promoter methylation was associated with lymph node staging, and resulted in poorer prognoses in patients with advanced gastric cancer. A total of 26 patients exhibited highly methylated PD-L1; in this group, the median progression-free survival time of patients receiving platinum/fluorouracil chemotherapy was 4.2 months longer than those receiving paclitaxel/fluorouracil chemotherapy, and the risk of disease progression in patients receiving paclitaxel/fluorouracil chemotherapy was 5.009 times higher compared with patients who received platinum/fluorouracil chemotherapy. Additionally, PD-L1 promoter methylation was significantly correlated with PD-L1 expression, and the progression of advanced gastric cancer. In conclusion, high methylation levels of the PD-L1 promoter region may be a faciliatory mechanism enabling gastric cancer tumorigenesis, and may also represent an independent prognostic factor for chemotherapeutic efficacy in patients with advanced gastric cancer.

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PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients

Cited by 72 publications

References 17 publications

Computational analysis of morphological and molecular features in gastric cancer tissues

Computational analysis of morphological and molecular features in gastric cancer tissues

LAG3(LAG-3,CD223) DNA methylation correlates with LAG3 expression by tumor and immune cells, immune cell infiltration, and overall survival in clear cell renal cell carcinoma

PD‑L1 gene promoter methylation represents a potential diagnostic marker in advanced gastric cancer

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