ArticlePloS one2020
Transcriptomic and proteomic intra-tumor heterogeneity of colorectal cancer varies depending on tumor location within the colorectum.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Multiregional transcriptomics identifies congruent consensus subtypes with prognostic value beyond tumor heterogeneity of colorectal cancer.Nature communications · 2024Article
- Predicting cervical lymph node metastasis in OSCC based on computed tomography imaging genomics.Cancer medicine · 2023Article
- Using Machine Learning Methods to Study Colorectal Cancer Tumor Micro-Environment and Its Biomarkers.International journal of molecular sciences · 2023Article
- Determination of temporal reproducibility and variability of cancer biomarkers in serum and EDTA plasma samples using a proximity extension assay.Clinical proteomics · 2022Article
- Microfluidic harvesting of breast cancer tumor spheroid-derived extracellular vesicles from immobilized microgels for single-vesicle analysis.Lab on a chip · 2022Article
- Orthotopic Versus Allotopic Implantation: Comparison of Radiological and Pathological Characteristics.Journal of magnetic resonance imaging : JMRI · 2022Article
- Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer.Cancers · 2021Article
- Tumour heterogeneity and evolutionary dynamics in colorectal cancer.Oncogenesis · 2021Review
- Radiogenomics in Colorectal Cancer.Cancers · 2021Review
- Proximity Extension Assay in Combination with Next-Generation Sequencing for High-throughput Proteome-wide Analysis.Molecular & cellular proteomics : MCP · 2021Article
- Biological mass spectrometry enables spatiotemporal 'omics: From tissues to cells to organelles.Mass spectrometry reviewsReview
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntra-tumor heterogeneity (ITH) of colorectal cancer (CRC) complicates molecular tumor classification, such as transcriptional subtyping. Differences in cellular states, biopsy cell composition, and tumor microenvironment may all lead to ITH. Here we analyze ITH at the transcriptomic and proteomic levels to ascertain whether subtype discordance between multiregional biopsies reflects relevant biological ITH or lack of classifier robustness. Further, we study the impact of tumor location on ITH.
methodsMultiregional biopsies from stage II and III CRC tumors were analyzed by RNA sequencing (41 biopsies, 14 tumors) and multiplex immune protein analysis (89 biopsies, 29 tumors). CRC subtyping was performed using consensus molecular subtypes (CMS), CRC intrinsic subtypes (CRIS), and TUMOR types. ITH-scores and network maps were defined to determine the origin of heterogeneity. A validation cohort was used with one biopsy per tumor (162 tumors).
resultsOverall, inter-tumor transcriptional variation exceeded ITH, and subtyping calls were frequently concordant between multiregional biopsies. Still, some tumors had high transcriptional ITH and were classified discordantly. Subtyping of proximal MSS tumors were discordant for 50% of the tumors, this ITH was related to differences in the microenvironment. Subtyping of distal MSS tumors were less discordant, here the ITH was more cancer-cell related. The subtype discordancy reflected actual molecular ITH within the tumors. The relevance of the subtypes was reflected at protein level where several inflammation markers were significantly increased in immune related transcriptional subtypes, which was verified in an independent cohort (Wilcoxon rank sum test; p<0.05). Unsupervised hierarchical clustering of the protein data identified large ITH at protein level; as the multiregional biopsies clustered together for only 9 out of 29 tumors.
conclusionOur transcriptomic and proteomic analyses show that the tumor location along the colorectum influence the ITH of CRC, which again influence the concordance of subtyping.
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