Detailed Abstract
[E-poster - Biliary & Pancreas (Biliary Disease/Surgery)]
[EP 133] Perineural Invasion Signature from Spatiotemporal Transcriptomics Data Shows Distinct Tumor Biology with Therapeutic Resistance in Advanced Biliary Tract Cancer
Sung Hwan LEE 1, Beodeul KANG 1, Kwang Il KIM 1
1 Department of Surgery, Bundang CHA, REPUBLIC OF KOREA, 2 Department of Medical Oncology, Bundang CHA, REPUBLIC OF KOREA, 3 Department of Pathology, Bundang CHA, REPUBLIC OF KOREA
Background : Perineural invasion is a well-known predictive pathologic factor associated with poor prognosis in pancreaticobiliary cancers. Recently, a new emerging technology, spatial transcriptomics, has emerged in cancer research to reveal complex tumor biology harboring in situ pathologic information of tumor microenvironment. This study aims to the identification of specific transcriptomic signatures for perineural invasion using the spatial transcriptomic technique with temporally collected patient samples.
Methods : Formalin-fixed paraffin-embedded blocks from initial biopsy and post-mortem autopsy samples (gallbladder, liver, peritoneum, lung) were enrolled in this study. Twenty-four areas of interest from six immunofluorescence slides with four morphology markers from the patient’s FFPE blocks were selected and the RNA sample for tumor, stroma, and tumor-infiltrating lymphocytes from each AOI was sequenced using GeoMx Human Whole Transcriptome Atlas platform.
Results : Tumor stroma and TILs showed distinct gene expression patterns according to their unique tumor microenvironments. Interestingly, the tumor samples showing perineural invasion have unique and discriminative transcriptomic profiles with differentially expressed gene sets. Inter and intra-tumoral heterogeneity with distinct tumor phenotypes were identified from comprehensive pathway analysis using single-sample gene-set enrichment analysis. The in-silico analysis for drug response prediction showed differential responses for currently available cancer therapeutics according to temporal tumor progression and spatial tumor context with their unique environments specific to perineural invasion.
Conclusions : Spatiotemporal transcriptomic analysis reveals clinically relevant tumor heterogeneity for perineural invasion in advanced biliary tract cancer. Inter and intra-tumoral heterogeneity showing different therapeutic opportunities warrant translational research for clinically relevant molecular deciphering with clinical samples in the era of precision surgical oncology.
Methods : Formalin-fixed paraffin-embedded blocks from initial biopsy and post-mortem autopsy samples (gallbladder, liver, peritoneum, lung) were enrolled in this study. Twenty-four areas of interest from six immunofluorescence slides with four morphology markers from the patient’s FFPE blocks were selected and the RNA sample for tumor, stroma, and tumor-infiltrating lymphocytes from each AOI was sequenced using GeoMx Human Whole Transcriptome Atlas platform.
Results : Tumor stroma and TILs showed distinct gene expression patterns according to their unique tumor microenvironments. Interestingly, the tumor samples showing perineural invasion have unique and discriminative transcriptomic profiles with differentially expressed gene sets. Inter and intra-tumoral heterogeneity with distinct tumor phenotypes were identified from comprehensive pathway analysis using single-sample gene-set enrichment analysis. The in-silico analysis for drug response prediction showed differential responses for currently available cancer therapeutics according to temporal tumor progression and spatial tumor context with their unique environments specific to perineural invasion.
Conclusions : Spatiotemporal transcriptomic analysis reveals clinically relevant tumor heterogeneity for perineural invasion in advanced biliary tract cancer. Inter and intra-tumoral heterogeneity showing different therapeutic opportunities warrant translational research for clinically relevant molecular deciphering with clinical samples in the era of precision surgical oncology.
SESSION
E-poster
E-Session 03/21 ALL DAY