胰腺癌中程序性死亡受体配体1（PD-L1）水平、TP53突变谱及生存结局因免疫营养状态而异。

PD-L1 levels, TP53 mutation profiles, and survival outcomes in pancreatic cancer differ by immune-nutritional status.

作者信息

Li Zheng, Ren Hu, Zhang Shihui, Sun Chongyuan, Li Zefeng, Niu Penghui, Fei He, Xing Cheng, Shi Susheng, Zhao Dongbing

机构信息

Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/ National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.

Department of Pathology, National Cancer Center, National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

出版信息

World J Surg Oncol. 2025 Apr 29;23(1):174. doi: 10.1186/s12957-025-03818-x.

DOI:10.1186/s12957-025-03818-x

PMID:40301983

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12042528/

Abstract

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits an immunosuppressive microenvironment coupled with malnutrition status. These features are instrumental in clinical management strategies for PDAC.

METHODS

Immune-nutrition status of patients was evaluated by integrating systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI). Individuals were divided into SII-PNI Status positive (SPS) group and SPS negative (SPS) group. Morphology of tissues was evaluated by hematoxylin-eosin (H&E) staining. Expression of PD-L1 and p53 was detected using immunohistochemistry (IHC).

RESULTS

In this study, 530 eligible patients (mean ± SD age, 60.5 ± 9.17 years, 296 males [55.8%], 74 SPS [14.0%]) were included. These patients exhibited a median survival of 24 months (1-, 3- and 5-year survival rate; 72.9%, 34.7% and 25.1%, respectively). In the multivariate analysis, independent indicators for outcomes were identified as tumor size, lymph node metastasis and SPS (all p <.01). After matching and adjusting, patients with SPS exhibited a notably reduced overall survival compared to those with SPS (14 vs. 25 months, p <.001), with hazard ratio (95% CI) of 1.79 (1.25-2.56). IHC revealed markedly elevated positive cell proportion of PD-L1 in SPS group (p <.01) and distinct p53 mutation patterns between SPS and SPS groups (p =.03). Morphology demonstrated a dissimilar trend of differentiation levels between the two groups (p =.08).

CONCLUSION

The findings suggest poorer outcome, higher PD-L1 expression and distinct p53 mutation status of patients with SPS. These patterns may contribute to PDAC management and strategic deployment of immunotherapy and targeted therapy.

摘要

背景

胰腺导管腺癌（PDAC）常表现出免疫抑制微环境并伴有营养不良状态。这些特征对PDAC的临床管理策略具有重要意义。

方法

通过整合全身免疫炎症指数（SII）和预后营养指数（PNI）来评估患者的免疫营养状态。个体被分为SII-PNI状态阳性（SPS）组和SPS阴性（SPS）组。通过苏木精-伊红（H&E）染色评估组织形态。使用免疫组织化学（IHC）检测PD-L1和p53的表达。

结果

本研究纳入了530例符合条件的患者（平均±标准差年龄，60.5±9.17岁，男性296例[55.8%]，SPS患者74例[14.0%]）。这些患者的中位生存期为24个月（1年、3年和5年生存率分别为72.9%、34.7%和25.1%）。在多变量分析中，确定为预后独立指标的是肿瘤大小、淋巴结转移和SPS（所有p<0.01）。经过匹配和调整后，与SPS患者相比，SPS患者的总生存期显著缩短（14个月对25个月，p<0.001），风险比（95%CI）为1.79（1.25 - 2.56）。免疫组织化学显示SPS组中PD-L1的阳性细胞比例显著升高（p<0.01），且SPS组和SPS组之间p53突变模式不同（p = 0.03）。形态学显示两组之间分化水平的趋势不同（p = 0.08）。