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Proteomics-Driven Risk Stratification in Stage III Colon Cancer: A Validated Prognostic Signature for Recurrence

Adel T Aref1, Mohashin Pathan1, Rosemary Habib2

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Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
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Summary
This summary is machine-generated.

A new six-protein risk score improves prognosis for stage-III colorectal cancer (CC) patients. This proteomic biomarker enhances risk stratification beyond standard clinical factors, aiding in personalized treatment decisions.

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Area of Science:

  • Oncology
  • Proteomics
  • Biomarker Discovery

Background:

  • Stage-III colorectal cancer (CC) lacks effective prognostic biomarkers for recurrence risk.
  • Proteomic profiling offers a quantitative method for improved risk stratification in CC.

Purpose of the Study:

  • To develop and validate a proteomic-based risk score for predicting recurrence in stage-III CC.
  • To assess the added prognostic value of the proteomic score to existing clinical factors.

Main Methods:

  • Proteomic analysis using data-independent acquisition mass spectrometry on stage-III CC tumor samples from three cohorts (n=759).
  • Development of a six-protein risk score (ITIH1, PPIE, LTBP1, KPNA2, IGFBP7, CKAP4) using Cox regression in a training cohort.
  • Validation of the risk score in two independent external cohorts.

Main Results:

  • The six-protein risk score significantly stratified patients into high- and low-risk groups for recurrence across all cohorts (HRs ranging from 1.8 to 5.7).
  • Integration of the proteomic score with clinical factors further improved prognostic accuracy.
  • A subgroup of patients with very low recurrence risk was consistently identified.

Conclusions:

  • The validated six-protein risk score enhances prognostic stratification for stage-III CC beyond standard clinical factors.
  • This proteomic biomarker provides a framework for risk-adapted clinical investigation.
  • Further research through prospective, treatment-stratified trials is needed to guide adjuvant therapy decisions.