肌肉减少症与胰腺导管腺癌不良预后和肿瘤浸润 CD8 阳性 T 细胞减少相关：一项回顾性分析。

Association of Sarcopenia with a Poor Prognosis and Decreased Tumor-Infiltrating CD8-Positive T Cells in Pancreatic Ductal Adenocarcinoma: A Retrospective Analysis.

机构信息

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

出版信息

Ann Surg Oncol. 2023 Sep;30(9):5776-5787. doi: 10.1245/s10434-023-13569-2. Epub 2023 May 16.

DOI:10.1245/s10434-023-13569-2

PMID:37191859

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10409680/

Abstract

BACKGROUND

Sarcopenia, defined as a loss of skeletal muscle mass and quality, is found in 30-65% of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis, and is a poor prognostic factor. However, it is yet to be evaluated why sarcopenia is associated with poor prognosis. Therefore, this study elucidated the tumor characteristics of PDAC with sarcopenia, including driver gene alterations and tumor microenvironment.

PATIENTS AND METHODS

We retrospectively analyzed 162 patients with PDAC who underwent pancreatic surgery between 2008 and 2017. We defined sarcopenia by measuring the skeletal muscle mass at the L3 level using preoperative computed tomography images and evaluated driver gene alteration (KRAS, TP53, CDKN2A/p16, and SMAD4) and tumor immune (CD4, CD8, and FOXP3) and fibrosis status (stromal collagen).

RESULTS

In localized-stage PDAC (stage ≤ IIa), overall survival (OS) and recurrence-free survival were significantly shorter in the sarcopenia group than in the non-sarcopenia group (2-year OS 89.7% versus 59.1%, P = 0.03; 2-year RFS 74.9% versus 50.0%, P = 0.02). Multivariate analysis revealed that sarcopenia was an independent poor prognostic factor in localized-stage PDAC. Additionally, tumor-infiltrating CD8 T cells in the sarcopenia group were significantly less than in the non-sarcopenia group (P = 0.02). However, no difference was observed in driver gene alteration and fib.rotic status. These findings were not observed in advanced-stage PDAC (stage ≥ IIb).

CONCLUSIONS

Sarcopenia was associated with a worse prognosis and decreased tumor-infiltrating CD8 T cells in localized-stage PDAC. Sarcopenia may worsen a patient's prognosis by suppressing local tumor immunity.

摘要

背景

在诊断时，30%-65%的胰腺导管腺癌（PDAC）患者存在骨骼肌减少症，定义为骨骼肌质量和质量的损失，这是预后不良的因素。然而，目前尚不清楚为什么骨骼肌减少症与预后不良有关。因此，本研究阐明了伴有骨骼肌减少症的 PDAC 的肿瘤特征，包括驱动基因改变和肿瘤微环境。

患者和方法

我们回顾性分析了 2008 年至 2017 年间接受胰腺手术的 162 例 PDAC 患者。我们使用术前 CT 图像测量 L3 水平的骨骼肌量来定义骨骼肌减少症，并评估了驱动基因改变（KRAS、TP53、CDKN2A/p16 和 SMAD4）和肿瘤免疫（CD4、CD8 和 FOXP3）和纤维化状态（基质胶原）。

结果

在局限性 PDAC（分期≤IIa）中，骨骼肌减少症组的总生存期（OS）和无复发生存期（RFS）明显短于非骨骼肌减少症组（2 年 OS 为 89.7%比 59.1%，P=0.03；2 年 RFS 为 74.9%比 50.0%，P=0.02）。多变量分析显示，骨骼肌减少症是局限性 PDAC 的独立不良预后因素。此外，骨骼肌减少症组的肿瘤浸润性 CD8 T 细胞明显少于非骨骼肌减少症组（P=0.02）。然而，在驱动基因改变和纤维化状态方面没有差异。这些发现在晚期 PDAC（分期≥IIb）中没有观察到。