PO.TB10.11 · 肿瘤生物学
癌症相关成纤维细胞亚型myCAF、iCAF和apCAF可能与胃癌患者的不良预后特征相关
Subtypes of cancer-associated fibroblasts, myCAF, iCAF, and apCAF, might be associated with adverse prognostic signature of patients with gastric cancer
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摘要 Abstract
中文摘要
背景：据报道，肿瘤微环境（TME）可能在包括胃癌（GC）在内的各种癌症的进展中发挥重要作用。癌症相关成纤维细胞（CAF）是TME的主要间质成分之一。CAF包括3种亚型，即肌成纤维细胞性CAF（myCAF）、炎性CAF（iCAF）和抗原呈递CAF（apCAF）。在本研究中，我们探讨了3种CAF亚型在GC中的临床病理学意义。
方法：本研究共收集1330例GC标本。使用针对myCAF、iCAF和apCAF的3种抗体进行免疫组织化学研究。成纤维细胞的染色水平采用半定量联合评分（0至6分）进行评分，该评分由强度评分（0至3分）和比例评分（0至3分）相加获得。
结果：myCAFs在T分期晚期、高淋巴管侵犯和高静脉侵犯的GC患者中显著（p<0.05）更为频繁。apCAFs在T分期晚期、淋巴结转移、远处转移和术后复发的GC患者中显著（p<0.05）更为频繁。相比之下，iCAF在有肿瘤浸润和术后复发少的GC患者中显著（p<0.05）更低。单变量Cox分析表明，myCAF+的总生存期（OS）显著更短（HR 1.97，95%CI 1.34-2.90，p<0.001），iCAF+的OS显著更短（HR 1.29，1.04-1.61，p=0.022），apCAF+的OS显著更短（HR 1.26，1.03-1.54，p=0.027）。在校正年龄、性别、T/N/M分期、组织学、细胞学和淋巴管侵犯后，仅myCAF+仍是OS的独立预后因素（HR 1.56，1.04-2.34，p=0.032），而iCAF+和apCAF+则不是（p>0.05）。myCAF、iCAF和apCAF+的三阳性特征赋予OS显著（p<0.001）的高风险（单变量Cox HR 2.98，95%CI 1.83-4.83；多变量Cox HR 2.48，95%CI 1.51-4.06）。
结论：在该GC队列中，myCAF、iCAF和apCAF各自与较低生存相关，且myCAF、iCAF和apCAF定义了一个独立的不良预后特征。协同的间质程序可能为CAF亚型状态作为预后因素提供依据。CAF亚型可能与GC患者的不良预后特征相关。
查看英文原文 English abstract
Background : It has been reported that the tumor microenvironment (TME) may play an important role for the progression of various carcinomas, including gastric cancer (GC). The cancer-associated fibroblast (CAF) is one of major stromal components of TME. CAF includes 3 subtypes such as myofibroblastic CAF (myCAF), inflammatory CAF (iCAF), and antigen-presenting CAF (apCAF). In this study, we investigated the clinicopathologic significance of 3 CAF subtypes in GC.
Methods: A total of 1330 GC specimens was collected in this study. Immunohistochemical study was performed using 3 antibodies against myCAF, iCAF, and apCAF. Staining level of fibroblasts was scored using a semi-quantitative combined score (from 0 to 6) which was obtained by the addiction of intensity score (0 to 3) and the proportion score (0-3).
Results : myCAFs were found significantly (p<0.05) frequent in GC patients with advanced T stage, high lymphatic invasion, and high venous invasion. apCAFs were found significantly (p<0.05) frequent in GC patients with advanced T stage, lymphatic metastasis, distant metastasis, and postoperative recurrence. In contrast, iCAF showed significantly (p<0.05) lower in GC patients with tumor infiltration and few postoperative recurrence. Univariable Cox indicated that myCAF+ showed significantly shorter overall survival (OS; HR 1.97, 95%CI 1.34-2.90, p<0.001), iCAF+ showed significantly shorter OS (HR 1.29, 1.04-1.61, p=0.022), and apCAF+ showed significantly shorter OS (HR 1.26, 1.03-1.54, p=0.027). After adjustment for age, sex, T/N/M stage, histology, cytology, and lymphatic invasion, only myCAF+ remained to be independent prognostic factor for OS (HR 1.56, 1.04-2.34, p=0.032), whereas iCAF+ and apCAF+ were not (p>0.05). The triple-positive signature of myCAF, iCAF, and apCAF+) conferred significantly (p<0.001) high risk for OS (univariable Cox HR 2.98, 95%CI 1.83-4.83; multivariate Cox HR 2.48, 95%CI 1.51-4.06).
Conclusions : In this GC cohort, myCAF, iCAF, and apCAF are individually associated with lower survival, and myCAF, iCAF, and apCAF defined an independent adverse prognostic signature. Cooperative stromal programs might provide rationale for CAF subtype status as a prognostic factor. CAF subtypes might be associated with adverse prognostic signature of GC patients.
利益披露 Disclosure
D. Ma, None..
H. Nishikubo, None..
T. Sano, None..
D. Imanishi, None..
T. Sakuma, None..
C. Fan, None..
Y. Yamamoto, None..
M. Yashiro, None.