Dataset Information

Stromal and epithelial proteome landscapes of pancreatic cancer predict poor prognosis and identify therapeutic options

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of relatively few tumor cells surrounded a heterocellular non-cancerous cell population embedded in extracellular matrix, collectively named stroma. Despite the recognition that the stroma is an important contributor to the typically poor outcome of PDAC, its analysis has been hampered by the analysis of bulk tissue. Similar issues have precluded meaningful analysis of the epithelial compartment. Here, we present the proteome analysis of a set of sixteen lasercapture microdissected PDAC samples, investigating tumor and stroma, together with bulk tumor samples, yielding the deepest PDAC proteomic to date.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stromal Cell Of Pancreas, Epithelial Cell Of Pancreas, Pancreas

DISEASE(S): Pancreatic Cancer

SUBMITTER: Sander Piersma

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD011289 | Pride | 2021-09-08

REPOSITORIES: Pride

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Publications

Microdissected pancreatic cancer proteomes reveal tumor heterogeneity and therapeutic targets.

Le Large Tessa Ys TY Mantini Giulia G Meijer Laura L LL Pham Thang V TV Funel Niccola N van Grieken Nicole Ct NC Kok Bart B Knol Jaco J van Laarhoven Hanneke Wm HW Piersma Sander R SR Jimenez Connie R CR Kazemier G G Giovannetti Elisa E Bijlsma Maarten F MF

JCI insight 20200806 15

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a relative paucity of cancer cells that are surrounded by an abundance of nontumor cells and extracellular matrix, known as stroma. The interaction between stroma and cancer cells contributes to poor outcome, but how proteins from these individual compartments drive aggressive tumor behavior is not known. Here, we report the proteomic analysis of laser-capture microdissected (LCM) PDAC samples. We isolated stroma, tumor, and bulk sample ...[more]

PMID: 32634123

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Project description:Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling we demonstrated that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 non-redundant genes that significantly discriminate the tumor stroma from non tumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up-regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix and Transforming Growth Factor beta (TGFM-NM-2) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increase expression of Collagen 4, Laminin, Osteopontin/SPP1, KIAA0101 and TGFM-NM-22 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of Osteopontin, TGFM-NM-22 and Laminin in the stroma of ICC was significantly correlated with patient overall survival. More importantly, multivariate analysis demonstrated that the stromal expression of Osteopontin was an independent prognostic marker for overall and disease-free survival. Conclusion: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidates biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression. 20 RNA samples were analyzed, from 10 patients with ICC. For each patient, RNA were isolated from laser capture microdissected (LCM) stroma from tumor and non tumor areas.

Project description:Tumor tissue heterogeneity is a well known feature of several solid tumors. Neuroblastic Tumors (NTs) is a group of paediatric cancers with a great tissue heterogeneity. Most of NTs are composed of undifferentiated, poorly differentiated or differentiating neuroblastic (Nb) cells with very few or absent Schwannian stromal (SS) cells: these tumors are grouped as Neuroblastoma (Schwannian stroma-poor). The remaining NTs are composed of abundant SS cells and classified as Ganglioneuroblastoma (Schwannian stroma-rich) intermixed or nodular and Ganglioneuroma. The importance to understand Nb and SS gene signatures in NTs, is to clarify the complex network mechanism of tumor growth and progression. In order to identify the Nb and SS cells gene signatures, we analyzed the gene expression profiling of 19 cases of neuroblastic tumors: 10 stroma poor (NTs-SP) and 9 stroma rich (NTs-SR), by high density oligonucleotide microarrays. Moreover, the analysis was performed in parallel on both whole and laser microdissected tumor samples: from 4 of 19 cases, was isolated different areas all composed of pure cellular populations. We performed genome wide expression analysis by using Affymetrix technology and we used two different approaches for data analysis: SAM (Significance Analysis of Microarrays) and a method based on Game Theory (GT), to identify genes differently expressed in SS and Nb cells. Differently from the SAM method, the analysis based on GT (Moretti et al. (2006)) gives the advantage of selecting relevant genes not only according to the expression profile of each single gene, but considering also gene interaction. Experiment Overall Design: Tissue samples from 10 primary neuroblastoma stroma-poor (NTs-SP) and 9 ganglioneuroblastoma/ganglioneuroma stroma-rich (NTs-SR) tumors, were obtained at diagnosis from patients at different clinical stage. Frozen samples of NTs-SP had a minimum content of 90% of malignant cells, while NTs-SR had more than 80-90% of schwannian stromal cells. Four out of 19 NTs: 2 neuroblastomas (Schwannian stoma-poor) and 2 ganglioneublastomas (Schwannian stroma-rich), were further analyzed with laser microdissection.

Dataset Information

Stromal and epithelial proteome landscapes of pancreatic cancer predict poor prognosis and identify therapeutic options

Publications

Microdissected pancreatic cancer proteomes reveal tumor heterogeneity and therapeutic targets.

Similar Datasets

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