α-SMA+ cancer-associated fibroblasts increased tumor enhancement ratio on contrast-enhanced multidetector-row computed tomography in stages I-III colon cancer

J Gastroenterol Hepatol. 2023 Dec;38(12):2111-2121. doi: 10.1111/jgh.16366. Epub 2023 Oct 3.

Abstract

Background and aim: Our prior research revealed that the tumor enhancement ratio (TER) on triphasic abdominal contrast-enhanced MDCT (CE-MDCT) scans was a prognostic factor for patients with stages I-III colon cancer. Building upon this finding, the present study aims to investigate the proteomic changes in colon cancer patients with varying TER values.

Methods: TER was analyzed on preoperative triphasic CE-MDCT scans of 160 stages I-III colon cancer patients. The survival outcomes of those in the low-TER and high-TER groups were compared. Proteomic analysis on colon cancer tissues was performed by mass spectrometry (MS) and verified by immune-histological chemistry (IHC) assays. In vivo, mouse xenograft models were employed to test the function of target proteins identified through the MS. CE-MDCT scans were conducted on mice xenografts, and the TER values were compared.

Results: Patients in the high-TER group had a significantly worse prognosis than those in the low-TER group. Proteomic analysis of colon cancer tissues revealed 153 differentially expressed proteins between the two groups. A correlation between TER and the abundance of α-SMA protein in tumor tissue was observed. IHC assays further confirmed that α-SMA protein expression was significantly increased in high-TER colon cancer, predominantly in cancer-associated fibroblasts (CAFs) within the cancer stroma. Moreover, CAFs promoted the growth of CRC xenografts in vivo and increased TER.

Conclusions: Our study identified the distinct protein changes in colon cancer with low and high TER for the first time. The presence of CAFs may promote the growth of colon cancer and contribute to an increased TER.

Keywords: Biomarker; Cancer-associated fibroblasts; Colonic neoplasms; Humans; Multidetector computed tomography.

MeSH terms

  • Animals
  • Cancer-Associated Fibroblasts* / metabolism
  • Cancer-Associated Fibroblasts* / pathology
  • Colonic Neoplasms* / diagnostic imaging
  • Colonic Neoplasms* / metabolism
  • Humans
  • Mice
  • Multidetector Computed Tomography / methods
  • Prognosis
  • Proteomics / methods