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.

IF 4.4 2区医学 Q1 ONCOLOGY

Cancers Pub Date : 2025-09-15 DOI:10.3390/cancers17183006

Toshinori Kobayashi, Mitsuaki Ishida, Hiroki Uehara, Shoichiro I, Norikazu Yamada, Yuto Igarashi, Chie Hagiwara, Yoshihiro Mori, Yoshinobu Hirose, Jun Watanabe

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引用次数: 0

Abstract

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.

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存在脂肪亲蛋白阳性的癌症相关成纤维细胞是一个独立的不良预后指标，并与结直肠癌患者的未成熟型结缔组织增生反应相关。

背景/目的：未成熟型（IM型）结缔组织增生反应（DR）是CRC预后较差的指标；然而，潜在的机制尚未明确。最近的研究表明，癌症相关成纤维细胞（CAFs）的能量代谢，包括脂质代谢，可以严重影响癌细胞的生长。脂质caf在结直肠癌中的预后意义尚未阐明。本研究旨在阐明脂质载癌细胞的存在是否与结直肠癌的DR类型和预后相关。方法：我们招募了pT3或pT4型结直肠癌患者，他们接受了手术切除而没有新辅助放化疗。采用免疫组织化学染色法检测亲脂素（ADP），以确定是否存在脂载CAFs。结果：该队列包括70例患者（49例男性，21例女性），中位年龄为74岁。37例（53%）患者出现adp阳性脂质CAFs。浸润前癌细胞中脂质CAFs的存在和ADP的表达与im型DR呈显著相关（p < 0.0001, p = 0.0063）。多因素分析显示，脂质CAFs的存在是一个独立的不良预后指标（风险比：3.65；95%可信区间：1.082-13.038;p = 0.0368）。结论：这些结果表明，脂质负载的CAFs的存在促进了癌症的进展、侵袭和转移，im型DR可能与富含脂质的肿瘤微环境有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancers Medicine-Oncology

CiteScore

8.00

自引率

9.60%

发文量

5371

审稿时长

18.07 days

期刊介绍： Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.