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Background Despite improvements in cancer management, most pancreatic cancers are still diagnosed at an advanced stage. We have recently identified promoter DNA methylation of the genes ADAMTS1 and BNC1 as potential blood biomarkers of pancreas cancer. In this study, we validate this biomarker panel in peripheral cell-free tumor DNA of patients with pancreatic cancer. Results Sensitivity and specificity for each gene are as follows: ADAMTS1 87.2% and 95.8% (AUC = 0.91; 95% CI 0.71–0.86) and BNC1 64.1% and 93.7% (AUC = 0.79; 95% CI 0.63–0.78). When using methylation of either gene as a combination panel, sensitivity increases to 97.3% and specificity to 91.6% (AUC = 0.95; 95% CI 0.77–0.90). Adding pre-operative CA 19-9 values to the combined two-gene methylation panel did not improve sensitivity. Methylation of ADAMTS1 was found to be positive in 87.5% (7/8) of stage I, 77.8% (7/9) of stage IIA, and 90% (18/20) of stage IIB disease. Similarly, BNC1 was positive in 62.5% (5/8) of stage I patients, 55.6% (5/9) of stage IIA, and 65% (13/20) of patients with stage IIB disease. The two-gene panel ( ADAMTS1 and/or BNC1 ) was positive in 100% (8/8) of stage I, 88.9% (8/9) of stage IIA, and 100% (20/20) of stage IIB disease. The sensitivity and specificity of the two-gene panel for localized pancreatic cancer (stages I and II), where the cancer is eligible for surgical resection with curative potential, was 94.8% and 91.6% respectively. Additionally, the two-gene panel exhibited an AUC of 0.95 (95% CI 0.90–0.98) compared to 57.1% for CA 19-9 alone. Conclusion The methylation status of ADAMTS1 and BNC1 in cfDNA shows promise for detecting pancreatic cancer during the early stages when curative resection of the tumor is still possible. This minimally invasive blood-based biomarker panel could be used as a promising tool for diagnosis and screening in a select subset of high-risk populations. Electronic supplementary material The online version of this article (10.1186/s13148-019-0650-0) contains supplementary material, which is available to authorized users.

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Background Malignant meningiomas are fatal and lack effective therapy. As M2 macrophages are the most prevalent immune cell type in human meningiomas, we hypothesized that normalizing this immunosuppressive population would be an effective treatment strategy. Methods We used CIBERSORTX to examine the proportions of 22 immune subsets in human meningiomas. We targeted the colony stimulating factor 1 (CSF1) or CSF1 receptor (CSF1R) axis, an important regulator of macrophage phenotype, using monoclonal antibodies (mAbs) in a novel immunocompetent murine model (MGS1) for malignant meningioma. RNA-seq was performed to identify changes in gene expression in the tumor microenvironment. Mass cytometry was used to delineate changes in immune subsets after treatment. We measured patients’ plasma CSF1 levels using ELISA and CSF1R expression using multiplex quantitative immunofluorescence in a human meningioma tissue microarray. Results Human meningiomas are heavily enriched for immunosuppressive myeloid cells. MGS1 recapitulates the tumor microenvironment of human meningiomas, including an abundance of myeloid cells, a paucity of infiltrating T cells, and low programmed-death ligand 1 (PD-L1) expression. Treatment of murine meningiomas with anti-CSF1/CSF1R, but not programmed cell death receptor 1 (PD-1), mAbs abrogate tumor growth. RNA-seq and mass cytometry analyses reveal a myeloid cell reprogramming with limited effect on T cells in the tumor microenvironment. CSF1 plasma levels are significantly elevated in human patients and CSF1R is highly expressed on CD163 + macrophages within the human tumor microenvironment. Conclusion Our findings suggests that anti-CSF1/CSF1R antibody treatment may be an effective normalization cancer immunotherapy for malignant meningiomas.