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The Concept of Stroma AReactive Invasion Front Areas (SARIFA) as a new prognostic biomarker for lipid-driven cancers holds true in pancreatic ductal adenocarcinoma.
- Source :
-
BMC cancer [BMC Cancer] 2024 Jun 26; Vol. 24 (1), pp. 768. Date of Electronic Publication: 2024 Jun 26. - Publication Year :
- 2024
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Abstract
- Background: Pancreatic ductal adenocarcinoma (PDAC) is a 'difficult-to-treat' entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion front areas), which are areas at the tumour invasion front lacking desmoplastic stroma reaction upon malignant invasion in the surrounding tissue, leading to direct contact between tumour cells and adipocytes. SARIFA showed its significance in gastric and colorectal carcinoma, revealing lipid metabolism alternations that promote tumour progression.<br />Methods: We reviewed the SARIFA status of 166 PDAC cases on all available H&E-stained tumour slides from archival Whipple-resection specimens. SARIFA positivity was defined as SARIFA detection in at least 66% of the available slides. To investigate alterations in tumour metabolism and microenvironment, we performed immunohistochemical staining for FABP4, CD36 and CD68. To verify and quantify a supposed delipidation of adipocytes, adipose tissue was digitally morphometrised.<br />Results: In total, 53 cases (32%) were classified as SARIFA positive and 113 (68%) as SARIFA negative. Patients with SARIFA-positive PDAC showed a significantly worse overall survival compared with SARIFA-negative cases (median overall survival: 11.0 months vs. 22.0 months, HR: 1.570 (1.082-2.278), 95% CI, p = 0.018), which was independent from other prognostic markers (p = 0.014). At the invasion front of SARIFA-positive PDAC, we observed significantly higher expression of FABP4 (p < 0.0001) and higher concentrations of CD68 <superscript>+</superscript> macrophages (p = 0.031) related to a higher risk of tumour progression. CD36 staining showed no significant expression differences. The adipocyte areas at the invasion front were significantly smaller, with mean values of 4021 ± 1058 µm <superscript>2</superscript> and 1812 ± 1008 µm <superscript>2</superscript> for the SARIFA-negative and -positive cases, respectively (p < 0.001).<br />Conclusions: SARIFA is a promising prognostic biomarker for PDAC. Its assessment is characterised by simplicity and low effort. The mechanisms behind SARIFA suggest a tumour-promoting increased lipid metabolism and altered immune background, both showing new therapeutic avenues.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Female
Male
Prognosis
Aged
Middle Aged
Neoplasm Invasiveness
Tumor Microenvironment
Lipid Metabolism
Antigens, Differentiation, Myelomonocytic metabolism
Antigens, CD metabolism
Stromal Cells metabolism
Stromal Cells pathology
CD36 Antigens metabolism
Adipocytes metabolism
Adipocytes pathology
Adult
Aged, 80 and over
CD68 Molecule
Carcinoma, Pancreatic Ductal pathology
Carcinoma, Pancreatic Ductal metabolism
Carcinoma, Pancreatic Ductal mortality
Biomarkers, Tumor metabolism
Pancreatic Neoplasms pathology
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms mortality
Fatty Acid-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 38926671
- Full Text :
- https://doi.org/10.1186/s12885-024-12519-9