Herein, we wanted to explore the molecular landscape of mucosal melanoma from different sites and identify potential molecular targets for future therapy. Mucosal melanomas (N = 40) from different sites (conjunctiva, sinonasal cavity, rectum, and vagina) were investigated. Targeted next-generation sequencing along with Nanostring gene expression profiling was performed. Genetically, conjunctival melanoma was characterized by BRAF-V600E (30%) and NF1 mutations (17%). Mucosal melanomas at nonsun-exposed sites harbored alterations in NRAS, KIT, NF1, along with atypical BRAF mutations. When comparing the gene expression profile of conjunctival melanoma and nonsun-exposed mucosal melanoma, 41 genes were found to be significantly deregulated. Programmed death-ligand 1 (PD-L1) presented a significant sixfold upregulation in conjunctival melanoma compared to the other mucosal melanomas. While melanomas of the sinonasal cavity, vagina, and rectum are molecularly similar, conjunctival melanoma is characterized by a higher frequency of BRAF-V600E mutations and differential expression of several genes involved in the immune response.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors. Most patients are diagnosed at an advanced stage where curative surgery is not an option. The aim of this study was to identify a panel of circulating proteins that could distinguish patients with PDAC from non-PDAC individuals. Experimental Design: We investigated 92 proteins known to be involved in inflammation, development, and progression of PDAC using the Olink immuno-oncology panel in serum samples from 701 patients with PDAC (stage I–IV), 102 patients with nonmalignant pancreatic diseases, and 180 healthy blood donors. Patients were included prospectively between 2008 and 2018. Plasma carbohydrate antigen 19-9 (CA19-9) was measured in all samples. The protein panels with the best diagnostic performances were developed by two bioinformaticians working independently, using LASSO and Ridge regression models. Results: Two panels of proteins (index I, containing 9 proteins + CA19-9, and index II, containing 23 proteins + CA19-9) were identified. Index I was able to discriminate patients with PDAC from all patients with non-PDAC, with a ROC AUC value of 0.92 [95% confidence interval (CI), 0.89–0.96] in the discovery cohort and 0.92 (95% CI, 0.87–0.97) in the replication cohort. For index II, the AUC value was 0.96 (95% CI, 0.95–0.98) in the discovery cohort and 0.93 (95% CI, 0.90–0.96) in the replication cohort. All nine serum proteins of index I were found in index II. Conclusions: This study identified two circulating protein indices with the potential to discriminate between individuals with and without PDAC.

Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. We aimed to find a prognostic protein signature for overall survival (OS) in patients with advanced PDAC, and to explore whether early changes in circulating-protein levels could predict survival. We investigated 92 proteins using the Olink Immuno-Oncology panel in serum samples from 363 patients with advanced PDAC. Protein panels for several survival cut-offs were developed independently by two bioinformaticians using LASSO and Ridge regression models. Two panels of proteins discriminated patients with OS < 90 days from those with OS > 2 years. Index I (CSF-1, IL-6, PDCD1, TNFRSF12A, TRAIL, TWEAK, and CA19-9) had AUCs of 0.99 (95% CI: 0.98–1) (discovery cohort) and 0.89 (0.74–1) (replication cohort). For Index II (CXCL13, IL-6, PDCD1, and TNFRSF12A), the corresponding AUCs were 0.97 (0.93–1) and 0.82 (0.68–0.96). Four proteins (ANGPT2, IL-6, IL-10, and TNFRSF12A) were associated with survival across all treatment groups. Longitudinal samples revealed several changes, including four proteins that were also part of the prognostic signatures (CSF-1, CXCL13, IL-6, TNFRSF12A). This study identified two circulating-protein indices with the potential to identify patients with advanced PDAC with very short OS and with long OS.

Background Proximity extension assay (PEA) is a novel antibody-based proteomic technology. Sparse data have been published concerning the matrix effect of serum vs. ethylenediamine tetraacetic acid (EDTA) plasma and the reproducibility of results obtained using PEA technology. Methods We analyzed samples with the PEA-based 92-plex Olink® immuno-oncology (I-O) assay. To estimate the matrix effect, we analyzed paired serum and EDTA plasma samples from 12 patients with biliary tract cancer. To evaluate the reproducibility, we used data from 7 studies, where 6–8 serum samples from patients with pancreatic cancer were used as bridging samples on 3 versions of the panel over a 2.5-years period. Results For the study of serum vs. plasma, 80 proteins were evaluable. The mean serum to EDTA plasma ratio ranged from 0.41–3.01. For 36 proteins, the serum and plasma values were not comparable due to high variability of the ratio, poor correlation, or possible concentration effect. For the bridging samples, the mean intra-study inter-assay coefficient of variation (CV) ranged from 11.3% to 26.1%. The mean inter-study CV was 42.0% before normalization and 26.2% after normalization. Inter-study results were well correlated (r ≥ 0.93), especially for studies using the same version of the panel (r ≥ 0.99). Conclusion For 44 of 92 proteins included in the Olink® I-O panel, the variation between results obtained using serum and EDTA plasma was constant and results were well correlated. Furthermore, samples could be stored for several years and used on different versions of the same PEA panel without it effecting results.

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