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 andp= 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.
背景/目的：未成熟型（IM型）结缔组织增生反应（DR）是结直肠癌（CRC）的不良预后指标，但其潜在机制尚未明确。近期研究表明，癌症相关成纤维细胞（CAFs）中的能量代谢（包括脂质代谢）对癌细胞生长具有关键影响。脂质富集CAFs在CRC中的预后意义尚未阐明。本研究旨在明确脂质富集CAFs的存在是否与CRC的DR类型及预后相关。方法：纳入接受手术切除且未接受新辅助放化疗的pT3或pT4期CRC患者。通过脂滴包被蛋白（ADP）免疫组化染色检测脂质富集CAFs的存在。结果：队列共70例患者（男性49例，女性21例），中位年龄74岁。37例患者（53%）观察到ADP阳性的脂质富集CAFs。脂质富集CAFs的存在及侵袭前沿癌细胞ADP表达均与IM型DR显著相关（分别为p<0.0001和p=0.0063）。多变量分析显示，脂质富集CAFs的存在是独立的不良预后指标（风险比：3.65；95%置信区间：1.082–13.038；p=0.0368）。结论：这些结果表明脂质富集CAFs的存在促进癌症进展、侵袭和转移，且IM型DR可能与富含脂质的肿瘤微环境相关。
肿瘤(癌症)患者之家