The seen and the unseen: Molecular classification and image based-analysis of gastrointestinal cancers

Minciuna, Corina-Elena; Tanase, Mihai; Manuc, Teodora; Tudor, Ştefan; Herlea, Vlad; Dragomir, Mihnea P.; Calin, George A.; Vasilescu, C

doi:10.1016/j.csbj.2022.09.010

Cited by 3 publications

(1 citation statement)

References 138 publications

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“…Even studies performed on fresh or fresh-frozen tissue ( Cancer Genome Atlas Network, 2012 ; ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, 2020 ) did not explicitly take morphological variants into consideration ( Shia et al, 2017 ). AI-based analysis of H&E slides ( Minciuna et al, 2022 ) or spatial transcriptomics ( Wang et al, 2023 ; Wood et al, 2023 ; Qi et al, 2022 ) offer a much better insight in CRC heterogeneity. Indeed, such studies have further confirmed a very high degree of intratumoral heterogeneity and have begun to establish new links between morphology and the underlying molecular programs4,5,26.…”

Section: Discussionmentioning

confidence: 99%

A quantitative tumor–wide analysis of morphological heterogeneity of colorectal adenocarcinoma

Dragomir,

Popovici,

Schallenberg

et al. 2024

Preprint

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Morphologic heterogeneity of colorectal adenocarcinoma (CRC) is poorly understood. Previously, we identified morphological patterns associated with CRC molecular subtypes, and showed that these patterns have distinct molecular motifs (Budinska et al., 2023). Here, we evaluated the heterogeneity of these patterns across CRC. Three pathologists evaluated dominant, secondary, and tertiary morphology on four different tissue blocks per tumor in a pilot set of 22 CRCs (n=88). An artificial intelligence (AI) image analysis tool was trained using the pathologist-rated tumors to assess the morphologic heterogeneity on an expanded set of 161 CRCs (644 images). Heterogeneity was expressed as a combination of morphology patterns (morphotypes) across slides and normalized Shannon's index (NSI). All pathologists agreed that the majority of tumors had 2-3 different dominant morphotypes, and that the complex tubular (CT) morphotype was the most common. AI analysis confirmed these observations in the full set. CT morphotype combined with all other dominant morphotypes within a tumor. Desmoplastic (DE) morphotype was rarely dominant and rarely combined with other dominant morphotypes. Mucinous (MU) was most often combined with solid/trabecular (TB) and papillary (PP). Most tumors showed medium or high NSI, but without clinical consequence. The proportion of DE morphotype was associated with higher T-stage, N-stage, metastasis, AJCC stage, and shorter relapse-free survival, and MU morphotype was associated with higher grade, right side, microsatellite instability, and shorter overall survival. In conclusion, we observed high intratumoral morphological heterogeneity of CRC, and that not heterogeneity per se, but the proportion of certain morphotypes showed associations with clinical outcome. This has implications for molecular profiling of CRC.

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Section: Discussionmentioning

confidence: 99%

A quantitative tumor–wide analysis of morphological heterogeneity of colorectal adenocarcinoma

Dragomir,

Popovici,

Schallenberg

et al. 2024

Preprint

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Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐Tumor Activity

Li,

Gu,

2024

Chemistry & Biodiversity

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Pancreatobililary cancers are fatal solid tumors that pose a significant threat to human life. It is imperative to investigate novel small molecule active compounds for controlling these cancers. Heterocyclic compounds (e.g. gemcitabine) and multi‐substituted alkenes (e.g. resveratrol) are commonly applied in tumor treatment. Researchers have proposed that the synthesis of new trisubstituted alkenes containing heteroaromatic rings by combining these two scaffolds may be a fresh strategy to develop new active molecules. In this study, we utilized alkenyl bromide and heteroaryl boronic acid as substrates, employing Suzuki coupling to generate a series of triarylethylenes featuring nitrogen, oxygen, and sulfur atoms. Through in vitro experiments, the results indicated that some compounds exhibited remarkable anti‐tumor efficacy (e.g. IC50[3be, GBC‐SD] = 0.13 µM and IC50[3be, PANC‐1] = 0.27 µM). The results further demonstrated that the antitumor efficacy of these compounds was dependent on the heteroatom, π‐system, skeleton‐bonding site, and substituent type.

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Therapeutic, Clinicopathological, and Molecular Correlates of PRKACA Expression in Gastrointestinal Cancers

Othaim,

Alasiri,

Alfahed

2024

Pharmaceuticals

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Background/Objectives: PRKACA alterations have clear diagnostic and biological roles in the fibrolamellar variant of hepatocellular carcinoma and a potential predictive role in that cancer type. However, the roles of PRKACA have not been comprehensively examined in gastric and colorectal cancers (GC and CRC). This study, therefore, sought to investigate the roles of PRKACA expression in GC and CRC. Methods: The clinico-genomic data of 441 GC and 629 CRC cases were analyzed for therapeutic, clinicopathological, and biological correlates using appropriate bioinformatics and statistical tools. Furthermore, the deregulation of PRKACA expression in GC and CRC was investigated using correlative and regression analyses. Results: The results showed that PRKACA expression subsets were enriched for gene targets of chemotherapeutics, tyrosine kinase, and β-adrenergic inhibitors. Moreover, high PRKACA expression was associated with adverse clinicopathological and genomic features of GC and CRC. Gene Ontology Enrichment Analysis also showed that PRKACA-high subsets of the GI cancers were enriched for the biological and molecular functions that are associated with cell motility, invasion, and metastasis but not cell proliferation. Finally, multiple regression analyses identified multiple methylation loci, transcription factors, miRNA species, and PRKACA copy number changes that deregulated PRKACA expression in GC and CRC. Conclusions: This study has identified potential predictive and clinicopathological roles for PRKACA expression in GI cancers and has added to the growing body of knowledge on the deregulation of PRKACA in cancer.

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The seen and the unseen: Molecular classification and image based-analysis of gastrointestinal cancers

Cited by 3 publications

References 138 publications

A quantitative tumor–wide analysis of morphological heterogeneity of colorectal adenocarcinoma

A quantitative tumor–wide analysis of morphological heterogeneity of colorectal adenocarcinoma

Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐Tumor Activity

Therapeutic, Clinicopathological, and Molecular Correlates of PRKACA Expression in Gastrointestinal Cancers

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