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Session:: Super Session Malignant Abstracts

SS100 - Interrogating the Biology of Local Recurrence in Rectal Cancer Employing Transcriptomic Expression Profiling in Patient Cohorts.

Saturday, May 9, 2026
3:07 PM - 3:15 PM ET

    Abstract Podium Presenter(s)

  • CK

    Chia Yew Kong, MB ChB MSc MRCS

    Honorary Clinical Lecturer in Surgery
    Academic Unit of Surgery, Glasgow Royal Infirmary
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    All of the relevant financial relationships listed below have been mitigated.
    This individual has no financial relationships with ineligible companies.

    • Author(s)

  • AM

    Ashley K. McCulloch, PhD

    Research Assistant
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    Disclosure information not submitted.

  • LH

    Lily Hillson, BS

    PhD candidate
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    Disclosure information not submitted.

  • TW

    Thomas A. Wright, MSci, PhD

    Research Assistant
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    Disclosure information not submitted.

  • GL

    Guang-Yu Lian, PhD

    Research associate
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    Disclosure information not submitted.

  • RM

    Ross McMahon, MBChB MRCS

    Clinical Lecturer in Surgery
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    Disclosure information not submitted.

  • NM

    Noori Maka, BScMedSci, MBChB, FRCPath

    Consultant Pathologist
    Queen Elizabeth University Hospital Glasgow
    Glasgow, Scotland, United Kingdom

    Disclosure information not submitted.

  • LG

    Laura E. Gould, MBChB, BSc, MRCS

    Surgical Registrar
    University College Hospital
    London, England, United Kingdom

    Disclosure information not submitted.

  • PD

    Philip Dunne, PhD

    Reader
    Johnston Cancer Research Centre, Queens University Belfast
    Belfast, Northern Ireland, United Kingdom

    Disclosure information not submitted.

  • JJ

    John Jenkins, MD MB ChB FRCS

    Consultant Colorectal Surgeon
    St Marks Hospital
    London, England, United Kingdom

    Disclosure information not submitted.

  • JE

    Joanne Edwards, PhD

    Professor of Translational Pathology
    University of Glasgow
    GLASGOW, Scotland, United Kingdom

    Disclosure information not submitted.

  • CS

    Colin W. Steele, PhD FRCS

    Consultant Surgeon & Clinical Senior Lecturer
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    Disclosure information not submitted.

    • Senior Author(s)

  • Campbell S. Roxburgh, PhD (he/him/his)

    Professor of Colorectal Surgical Oncology
    University of Glasgow
    University of Glasgow
    Glasgow, Scotland, United Kingdom

    All of the relevant financial relationships listed below have been mitigated.
    Agenus: Advisor or Review Panel Member (Terminated); AstraZeneca: Clinical Trial Investigator (Ongoing), Grant/Research Support (Ongoing); GSK: Advisor or Review Panel Member (Ongoing), Clinical Trial Investigator (Ongoing), Grant/Research Support (Ongoing); Intuitive Surgical: Teaching (Ongoing); Varian: Grant/Research Support (Ongoing)

All of the relevant financial relationships listed below have been mitigated.
Chia Yew Kong, MB ChB MSc MRCS: This individual has no financial relationships with ineligible companies.
Campbell S. Roxburgh, PhD: Agenus: Advisor or Review Panel Member (Terminated); AstraZeneca: Clinical Trial Investigator (Ongoing), Grant/Research Support (Ongoing); GSK: Advisor or Review Panel Member (Ongoing), Clinical Trial Investigator (Ongoing), Grant/Research Support (Ongoing); Intuitive Surgical: Teaching (Ongoing); Varian: Grant/Research Support (Ongoing)
Purpose/Background: Despite modern multi-modal therapy for rectal cancer, a proportion (up to 10%) develop local recurrence (LR). Management of LR remains challenging; surgery is often limited to ultra-radical options and systemic treatments are biologically untargeted. Current risk factors for local recurrence (LR) are confined to clinical staging criteria at the time of primary diagnosis and form the basis for neoadjuvant therapy decisions. No current consideration is given to tumor biology. In order to improve our understanding of the biological characteristics underpinning local recurrence in rectal cancer we planned a study interrogating transcriptomic pathways and traits associated with two cohorts of primary rectal tumors with (a) absence of LR and (b) presence of LR) as well as a 3rd unique cohort of locally recurrent tumors themselves. We hope to identify signatures that could inform future biomarker or therapeutic strategy development.

Methods/Interventions: An archival cohort of formalin fixed paraffin embedded (FFPE) resectional tumour specimens comprising rectal cancer across the local recurrence disease spectrum ((1) primary non-recurrent rectal cancer (PN), (2) primary rectal cancer with future local recurrence (PR) and (3) locally recurrent rectal cancer (LR)) was curated from two high-volume UK centres (Glasgow Royal Infirmary and St Marks’ Hospital, London). Full FFPE tumour sections were macrodissected to enrich for tumour prior to ribodeoxy-nucleic acid (RNA) extraction. Bulk sequencing of extracted RNA was performed using Illumina Nova-seq. All analyses were performed on R using the following packages: ‘DESeq’, ‘ClusterProfiler’, “CMSClassifier’ & ‘MCPcounter’. The MSigDB Hallmark signature collection was used for gene set enrichment analysis (GSEA)(1).

Results/Outcomes: 102 tumours were eligible for analysis (28 PN, 38 PR and 36 LR). The PR group had the highest proportion of neoadjuvant treatment (71.1% vs PN 25% & LR 44.4%), involved surgical margins (23.7% vs PN 3.6%), low rectal tumours (30.8% vs PN 3.8%) and poor differentiation (10.5% vs PN 0%) (all P< 0.05). GSEA revealed ‘MYOGENESIS’, ‘EPITHELIAL MESENCHYMAL TRANSITION’ and ‘KRAS SIGNALING DN’ pathways to be the top 3 enriched pathways in PR versus PN. In LR versus all primary tumours, the top 3 enriched pathways were ‘EPITHELIAL MESENCHYMAL TRANSITION, ‘MYOGENESIS’ and ‘HYPOXIA’. The top 3 most downregulated pathways in both PR vs PN and LR versus primary tumours pairwise comparisons were consistent: ‘MYC TARGETS V1’, ‘E2F TARGETS’ and ‘G2M CHECKPOINT’.
LR was associated with the highest proportion of Consensus-Molecular-Subtype (CMS) 4 tumours (54.2% vs PR 45.8% vs PN 0%) (P < 0.001).
Microenvironment cell population counter revealed that LR and PR was associated with lower B cell, T cell as well as higher fibroblast, neutrophil and monocyte populations (all P< 0.05).

Conclusion/Discussion: Local recurrence in rectal cancer is associated with stereotypical high-risk biological pathways including epithelial mesenchymal transition and myogenesis, downregulated proliferative pathways and an enrichment in CMS4 tumours. In terms of tumour microenvironment, LR was associated with a dysregulated adaptive immune response and fibroblast enrichment. Importantly, these features are present in the primary tumours and suggest early biomarker of LR could be developed. These results also present important research avenues for testing and developing novel therapeutics specifically targeting LRRC. References 1. Liberzon et al. Cell Syst 2015;1(6):417-425