Presence of Adipophilin-Positive Cancer-Associated Fibroblasts Is an Independent Poor Prognostic Indicator and Is Correlated with Immature-Type Desmoplastic Reaction in Patients with Colorectal Cancer.

Background/objectives: Immature-type (IM type) desmoplastic reaction (DR) is a poor prognostic indicator of CRC; however, the underlying mechanism has not yet been clarified. Recent studies have demonstrated that energy metabolism, including lipid metabolism, in cancer-associated fibroblasts (CAFs) can critically impact cancer cell growth. The prognostic significance of lipid-laden CAFs in CRC has not yet been elucidated. This study aimed to clarify whether the presence of lipid-laden CAFs correlates with the DR type and prognosis in CRC.

Methods: We enrolled patients with pT3 or pT4 CRC who underwent surgical resection without neoadjuvant chemoradiotherapy. Immunohistochemical staining for adipophilin (ADP) was performed to determine the presence of lipid-laden CAFs.

Results: The cohort included 70 patients (49 men and 21 women) with a median age of 74 years. ADP-positive lipid-laden CAFs were observed in 37 patients (53%). The presence of lipid-laden CAFs and ADP expression in carcinoma cells at the invasive front was significantly correlated with IM-type DR (p < 0.0001 and p = 0.0063, respectively). The presence of lipid-laden CAFs was an independent poor prognostic indicator based on multivariate analysis (hazard ratio: 3.65; 95% confidence interval: 1.082-13.038; p = 0.0368).

Conclusions: These results suggest that the presence of lipid-laden CAFs enhance cancer progression, invasion, and metastasis, and that IM-type DR might be related to the lipid-rich tumor microenvironment.