DNA methylation classifier to diagnose pancreatic ductal adenocarcinoma metastases from different anatomical sites
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ABSTRACT:
PROVIDER: PRJNA1057838 | ENA |
REPOSITORIES: ENA
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Project description:Background We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites. Methods For this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the updated version of the classifier on a validation set, which consisted of a biological cohort (n = 3579) and a technical one (n = 15). We then assessed the performance of the classifier on a test set, which included a positive control cohort of 16 PAAD metastases from various sites and a cohort of 124 negative control samples consisting of 96 breast cancer metastases from 18 anatomical sites and 28 carcinoma metastases to the brain. Results The updated PAAD-iCCA-Classifier achieved 98.21% accuracy on the biological validation samples, and on the technical validation ones it reached 100%. The classifier also correctly identified 15/16 (93.75%) metastases of the positive control as PAAD, and on the negative control, it correctly classified 122/124 samples (98.39%) for a 97.85% overall accuracy on the test set. We used this DNA methylation dataset to explore the organotropism of PAAD metastases and observed that PAAD liver metastases are distinct from PAAD peritoneal carcinomatosis and primary PAAD, and are characterized by specific copy number alterations and hypomethylation of enhancers involved in epithelial-mesenchymal-transition. Conclusions The updated PAAD-iCCA-Classifier (available at https://classifier.tgc-research.de/) can accurately classify PAAD samples from various metastatic sites and it can serve as a diagnostic aid.
2024-11-20 | GSE252130 | GEO
Project description:Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is difficult. We hypothesized that DNA-methylation based machine-learning algorithms may be able to perform this task. We assembled genome-wide DNA-methylation data for iCCA, PAAD, and normal bile from publicly available sources. We used an internal cohort consisting of 72 samples to test our classifier.
2023-06-05 | GSE217384 | GEO
Project description:A genome-wide DNA methylation-based classifier differentiates intrahepatic cholangiocarcinomas from hepatic metastases of pancreatic ductal adenocarcinoma
| PRJNA898779 | ENA
Project description:Breast cancer molecular subtypes preferentially metastasize to specific organs and the anatomical location of the metastasis is associated with the length of survival post-recurrence. We used microarrays to provide a detailed characterization of breast cancer site-specific metastases with particular focus on identifying genes predictive of breast cancer liver metastatic proprnsity We performed global gene expression profiling on fine-needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of first-line chemotherapy for locally advanced or metastatic breast cancer. Samples were collected before commencement of treatment.
2013-12-02 | E-GEOD-46141 | biostudies-arrayexpress
Project description:Breast cancer molecular subtypes preferentially metastasize to specific organs and the anatomical location of the metastasis is associated with the length of survival post-recurrence. We used microarrays to provide a detailed characterization of breast cancer site-specific metastases with particular focus on identifying genes predictive of breast cancer liver metastatic proprnsity
2013-12-02 | GSE46141 | GEO
Project description:To determine whether breast cancer molecular subtypes and tumor characteristics with demonstrated significance in a primary tumor setting can also confer clinically relevant information in breast cancer metastases. We assessed previously published gene expression modules of seven biological processes and the intrinsic subtypes (PAM50). The translational aspect of the Swedish randomized TEX trial included 112 patients with at least one biopsy from morphologically confirmed loco-regional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up and metastasis gene expression information (Affymetrix array GPL10379). We performed global gene expression profiling on fine-needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of first-line chemotherapy for locally advanced or metastatic breast cancer. Samples were collected before commencement of treatment.
2014-11-03 | E-GEOD-56493 | biostudies-arrayexpress
Project description:Background: Mortality rates of pancreatic cancer remain high, which is mainly due to advanced disease and metastasis. We hypothesized that DNA copy number alteration are enriched in metastatic cells compared to autologous primary tumors, which may inform on cancer-related pathways possibly serving as potential targets for specific therapies. We investigated 18 pancreatic ductal adenocarcinomas, including 39 lymph node and 5 distant metastases after surgical resection. Analysis was performed with array-based comparative genomic hybridization. Results: Metastases acquire a higher frequency of CNAs with the highest in distant metastasis (OM: median=42, LNM: median=23, PT: median=17). In LNM, gains were prevalent on chromosome bands 8q11.23-q24.3, 12q14.1, 17p12.1, 21q22.12, and losses on 3p21.31, 4p14, 8p23.3-p11.21,17p12-11.2. Genes on amplified regions are involved in cancer-related pathways such as WNT-signaling, also involved in metastasis. Conclusions: Pancreatic cancers show a high degree of intratumor heterogeneity, which could lead to resistance of chemotherapy and worse outcome. ACGH analysis reveals regions preferentially gained or lost in synchronous metastases encoding for genes involved in cancer-related pathways, which could lead to novel therapeutic opportunities.
2017-10-01 | GSE103787 | GEO
Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity. Methods and Results: We conducted RNA sequencing for synchronous surgically resected PTs and the paired HMs from 14 hepatic oligometastatic PDACs and experimentally validated our findings in specimens from 35 of such cases. The comprehensive analysis of gene expressions showed largely similarity between PTs and HMs. However, hepatic metastases also showed unique characteristics, such as stronger abilities of proliferation, downregulation of EMT activity and metabolic rewiring. More interesting, altered tumor microenvironments were observed in hepatic metastases, especially higher proportion of tumor infiltrating M2 macrophage and upregulation of complement cascade. Further experiments demonstrate that expression of C1q increased continuously from normal to PTs to HMs, C1q was mainly produced from M2 macrophage, and C1q promoted migration and invasion of PDAC cells. Conclusion: Taken together, we found potential factors that contribute to different stages of PDAC metastasis. Our study broadens the understandings of molecular mechanisms driving PDAC metastasis.
2020-06-02 | GSE151580 | GEO
Project description:Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. The transcriptomic study comprises 16 samples from Lymph node metastasis from infiltrating ductal breast carcinoma, 18 samples from Primary node-positive infiltrating ductal,7 samples from Primary node-negative infiltrating ductal and 3 samples from Unaffected lymph node were included. Their RNA was isolated and prepared for hybridization to human Affymetrix GeneChip arrays.
2013-03-05 | E-GEOD-44408 | biostudies-arrayexpress
Project description:Interventions: Group 1: anatomical resection of liver metastases (almost complete removal of the affected liver segment)
Group 2: non-anatomical resection of liver metastases (removal of the liver metastases with a sufficient safety margin, but independent of the borders of the affected segment)
Primary outcome(s): Intrahepatic disease-free survival (iDFS): Time from operation date to date of disease recurrence in the liver, followed up at intervals of three months for a maximum duration of 24 months or until death. Any new, solid lesion in the liver after resection of all CRLM that fulfils imaging criteria (CT, MRI) of a metastasis is counted as an iDFS event.
Study Design: Allocation: Randomized controlled study; Masking: Blinded (masking used); Control: active; Assignment: parallel; Study design purpose: treatment
| 2438289 | ecrin-mdr-crc