# Proteomic Analysis of FFPE Tissue Samples Identifies Potential Molecular Mechanisms Mediating Resistance to Radiotherapy in Rectal Cancer

## TL;DR

This study identifies proteins linked to resistance to radiotherapy in rectal cancer, which could help predict treatment response and guide personalized therapy.

## Contribution

The study identifies novel proteins associated with radioresistance in rectal cancer using proteomic analysis of FFPE tissue.

## Key findings

- 1685 proteins were identified, with 221 differentially expressed in tumor vs. normal tissue.
- Proteins like CEACAM, MCM complex components, and CD55 were upregulated in nonresponders to chemoradiation.
- Autophagy and DNA repair-related proteins (e.g., TOM1, TP53BP1) distinguished non- and complete responders.

## Abstract

Chemoradiation prior
to surgery in locally advanced rectal cancer
is the current standard therapy but is not effective in all rectal
cancer patients. Prognostic markers supporting patient stratification
with respect to clinical response would therefore be desirable. The
aim of this study was to investigate pathophysiological mechanisms
underlying radioresistance and to identify potential prognostic markers
by comparative proteome profiling. Therefore, formalin fixed paraffin-embedded
tissue (FFPE) samples from rectal tumors (n = 50)
and normal control tissue (n = 39) of nonresponders
and responders to neoadjuvant chemoradiation were analyzed. As a result,
1685 robustly identified proteins were further evaluated. Comparing
tumor with corresponding control samples revealed 221 differentially
expressed proteins (FDR < 0.05) with FTL, PCOLCE, and RCN3 being
most striking in tumor tissue. CEACAM 1, 5, and 6, as well as MCM
protein complex components, were significantly up-regulated in tumor
tissue of nonresponders. The autophagic activity-related and DNA damage
repair proteins TOM1, CAPNS1, TP53BP1, HS1BP3, as well as COTL1 and
DCPS, discriminated non- and nearly complete from complete responders.
In the tumor-surrounding tissue of nonresponders, the innate immune
response-suppressing protein CD55 was found specifically up-regulated.
These proteins may serve as prognostic markers and potential therapeutic
targets, requiring further validation in prospective studies.