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Multi-omics-driven discovery of invasive patterns and treatment strategies in CA19-9 positive intrahepatic cholangiocarcinoma. | LitMetric

AI Article Synopsis

  • * Comprehensive data analysis was conducted across multiple cohorts using various techniques, uncovering significant differences between CA19-9 positive and negative ICC, including mutation rates and poor survival rates for the positive group.
  • * The study highlights the importance of glycolysis-related cell clusters in CA19-9 positive ICC, which contribute to aggressive cancer behavior, and identifies six drugs that may be effective for targeted therapies, paving the way for personalized treatment strategies.

Article Abstract

Background: Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with a poor prognosis, predominantly CA19-9 positive. High CA19-9 levels correlate with increased aggressiveness and worse outcomes. This study employs multi-omics analysis to reveal molecular features and identify therapeutic targets of CA19-9 positive ICC, aiming to support individualized treatment.

Methods: Data from seven clinical cohorts, two whole-exome sequencing cohorts, six RNA sequencing/microarray cohorts, one proteomic cohort, 20 single-cell RNA sequencing samples, and one spatial transcriptome sample were analyzed. Key findings were validated on tissue microarrays from 52 ICC samples.

Results: CA19-9 positive ICC exhibited poorer OS (median 24.1 v.s. 51.5 months) and RFS (median 11.7 v.s. 28.2 months) compared to negative group (all P < 0.05). Genomic analysis revealed a higher KRAS mutation frequency in the positive group and a greater prevalence of IDH1/2 mutations in the negative group (all P < 0.05). Transcriptomic analysis indicated upregulated glycolysis pathways in CA19-9 positive ICC. Single-cell analysis identified specific glycolysis-related cell subclusters associated with poor prognosis, including Epi_SLC2A1, CAF_VEGFA, and Mph_SPP1. Higher hypoxia in the CA19-9 positive group led to metabolic reprogramming and promoted these cells' formation. These cells formed interactive communities promoting epithelial-mesenchymal transition (EMT) and angiogenesis. Drug sensitivity analysis identified six potential therapeutic drugs.

Conclusions: This study systematically elucidated the clinical, genomic, transcriptomic, and immune features of CA19-9 positive ICC. It reveals glycolysis-associated cellular communities and their cancer-promoting mechanisms, enhancing our understanding of ICC and laying the groundwork for individualized therapeutic strategies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568536PMC
http://dx.doi.org/10.1186/s12967-024-05854-9DOI Listing

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