Abstract
Cholangiocarcinoma remained a severe threat to human health. Deciphering the genomic and/or transcriptomic profiles of tumor has been proved to be a promising strategy for exploring the mechanism of tumorigenesis and development, which could also provide valuable insights into Cholangiocarcinoma. However, little knowledge has been obtained regarding to how the alteration among different omics levels is connected. Here, using whole exome sequencing and transcriptome sequencing, we performed a thorough evaluation for the landscape of genome and transcriptome in cholangiocarcinoma and illustrate the alteration of tumor on different biological levels. Meanwhile, we also identified the clonal structure of each included tumor sample and discovered different clonal evolution patterns related to patients’ survival. Furthermore, we extracted subnetworks that were greatly influenced by tumor clonal/subclonal mutations or transcriptome change. The topology relationship between genes affected by genomic/transcriptomic changes in biological interaction networks revealed that alteration of genome and transcriptome was highly correlated, and somatic mutations located on important genes might affect the expression of numerous genes in close range.
Highlights
Cholangiocarcinoma (CCA), a heterogeneous malignant tumor currently acknowledged as the second most common primary liver cancer, showed increasing incidents worldwide during past decades
Whole-exome and transcriptome sequencing were performed for acquired tissue samples
Transcriptome Analysis Revealed Alteration in Pathways Enriched in CCA Clonal Evolutionary Process we explored the transcriptome landscape to evaluate the change in gene expression during CCA development
Summary
Cholangiocarcinoma (CCA), a heterogeneous malignant tumor currently acknowledged as the second most common primary liver cancer, showed increasing incidents worldwide during past decades. CCA is considered as a rare cancer in most countries due to its relative low incidents (lower than 6 cases per 100,000 people), the situations are different in several countries including China and Thailand, where CCA incident reaches an exceptionally high level. Among all CCA cases, intrahepatic cholangiocarcinoma takes up only 10%, while a minority (15%) of these patients were diagnosed with resectable disease status (Cardinale et al, 2018; Rizvi et al, 2018). Multi-Omic Analysis of Cholangiocarcinoma the heterogeneity of tumor on multiple levels (e.g., genomic, transcriptional) often resulted in resistance to therapy, which further intensifies the challenge of CCA treatments. A thorough evaluation of the landscape on CCA genome and transcriptome could provide clinically related insights into the genesis and progression of CCA
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