EP926 - Skeletal Muscle as a Window into Advanced Colorectal Cancer Progression: A Transcriptomic Study

ePoster Presenter(s)

• 

  Vashti Bandy, MD (she/her/hers)

  General Surgery Resident
  Virginia Commonwealth University
  Virginia Commonwealth University
  Richmond, VA, United States

  Disclosure information not submitted.

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Author(s)

• AP

  Arunima Punjala, MD

  Resident Physician
  VCU Health System
  Richmond, Virginia, United States

  Disclosure information not submitted.
• VV

  Vignesh Vudatha, MD MS

  Resident
  VCU Health
  Richmond, Virginia, United States

  Disclosure information not submitted.
• PB

  Praveen Bhoopathi, n/a

  Asst Professor
  Department of Surgery
  Richmond, Virginia, United States

  Disclosure information not submitted.
• LF

  Leopoldo Fernandez, Assistant Professor

  Attending Surgeon
  Virginia Commonwealth University
  Glen Allen, Virginia, United States

  Disclosure information not submitted.
• AJ

  Andrew Judge, PhD

  Professor
  University of Florida
  Gainesville, Florida, United States

  Disclosure information not submitted.
• MD

  Mikhail Dozmorov, PhD

  Associate professor
  Virginia Commonwealth University
  Richmond, Virginia, United States

  Disclosure information not submitted.
• KT

  Katarzyna Tyc, PhD

  Assistant Professor
  Virginia Commonwealth University
  Richmond, Virginia, United States

  Disclosure information not submitted.

Senior Author(s)

• JT

  Jose Trevino, MD

  Attending
  Virginia Commonwealth University
  Richmond, Virginia, United States

  Disclosure information not submitted.

Purpose/Background: Cancer cachexia is a complex metabolic syndrome characterized by severe muscle loss, reduced physical function, and diminished therapeutic response. Despite its clinical impacts, the transcriptional landscape of cachexia in patients with advanced peritoneal carcinomatosis from metastatic colorectal cancer (pmCRC) remains poorly defined. Our study aims to characterize alterations in skeletal muscle with associated cachexia in pmCRC patients.

Methods/Interventions: Muscle biopsies were obtained from 17 pmCRC patients consented for IRB tissue collection and undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), classified as myopenic (n=7) or non-myopenic (n=11) based on skeletal muscle index (SMI cm2/m2). Biopsies were sent for RNA sequencing and differential expression analysis was performed utilizing statistical algorithms within edgeR software. We compared the two cohorts and selected differentially expressed genes (DEGs) with significantly increased or decreased expression (>2-fold change and p-value < 0.05). Enrichment analysis identified gene sets and pathways relevant to cachexia pathophysiology. Last, survival analysis was performed to assess the prognostic value of identified DEGs in predicting patient outcomes.

Results/Outcomes: Our analysis revealed 231 genes with significant expression changes, including 75 upregulated and 156 downregulated genes in the myopenic group. Enrichment analysis exhibited several pathways involved in immune cell signaling. Overall survival analysis revealed associations with survival outcomes for seven DEGs-six of which have associated prognostic value in colorectal cancer or other cancer variants. High expression of two DEGs and low expression of the remaining prognostic genes were linked with poor survival in our patient cohort.

Conclusion/Discussion: Our study highlights molecular features of cancer-induced cachexia in pmCRC and several potential diagnostic and prognostic biomarkers.

Heatmap visualization of DEGs in myopenic vs. non-myopenic patients
Heatmap displaying patient-specific expression profiles of the 231 DEGs (differentially expressed genes). Patients are arranged along the columns and classified into non-myopenic (green) vs myopenic (orange) groups. Expression values are shown as relative intensities, with blue indicating lower expression and red indicating higher expression, highlighting patterns that distinguish the two cohorts.
Genes with known prognostic value in other cancer variants were differentially expressed between myopenic and non-myopenic cohorts
Kaplan-Meier analysis of DEGs identified seven (7) prognostic genes, each significantly downregulated in the myopenic cohort. With exception of MCTP2, these genes have established relevance in cancer biology, including colorectal cancer (MAP9), renal clear cell carcinoma (FCGR2A, PIK3R6), hepatocellular carcinoma (NTF3), oral squamous cell carcinoma (MTCP2), and pancreatic adenocarcinoma (PLS1).