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联合评估间质 TIL(肿瘤浸润淋巴细胞)与肿瘤 peroxiredoxin 4 表达改善术后胰腺癌患者的预后分层

英文原题:Combined assessment of stromal tumor infiltrating lymphocytes and tumor peroxiredoxin 4 expression improved prognostic stratification in postoperative pancreatic cancer patients.

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Combined assessment of stromal tumor infiltrating lymphocytes and tumor peroxiredoxin 4 expression improved prognostic stratification in postoperative pancreatic cancer patients.

PubMed 2026/04/16(内容时间) Diagn Pathol Q1 · IF 3.5(JCR 2025)

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研究概要

基质 TIL 和 PRDX4 似乎分别捕捉了 PC 的免疫和氧化还原互补特征。它们的联合评估可能改善预后分层,并有助于识别一个潜在的氧化还原相关、免疫排斥亚组,该亚组预后特别差。

研究思路结论见上方概要

胰腺癌(PC)以深度免疫抑制和显著的生物学异质性为特征。间质TIL(肿瘤浸润淋巴细胞)(TILs)反映宿主抗肿瘤免疫,而过氧化物还原酶4(PRDX4)代表肿瘤氧化还原适应。然而,二者的联合预后价值尚不清楚。

我们回顾性分析了138例切除的PC病例。在苏木精-伊红(H&E)切片上评估间质TIL密度,并通过免疫组化评估肿瘤PRDX4表达。使用ROC衍生的阈值将这两种标志物分为高和低两组。患者进一步分为四个整合亚组:TIL-高/PRDX4-低(TH-PL)、TIL-高/PRDX4-高(TH-PH)、TIL-低/PRDX4-低(TL-PL)和TIL-低/PRDX4-高(TL-PH)。分析了与临床病理特征和疾病特异性生存(DSS)的关联。

高 TIL 密度与较晚的病理分期较少相关,并显著改善 DSS,而高 PRDX4 表达与淋巴血管和神经周围侵犯以及晚期分期相关。观察到 TILs 与 PRDX4 之间呈负相关。整合亚组分析揭示了不同的预后模式:TL-PH 亚组显示最差的 DSS,而 TH-PL 亚组表现出最有利的结局。在多变量 Cox 模型中,TL-PH 亚组仍然是 3 年和 5 年 DSS 的独立不良预后因素,而 TH-PL 亚组显示出保护作用,尤其是在 3 年时。

展开英文摘要原文

Pancreatic cancer (PC) is characterized by profound immunosuppression and marked biological heterogeneity. Stromal tumor-infiltrating lymphocytes (TILs) reflect host antitumor immunity, whereas peroxiredoxin 4 (PRDX4) represents tumor redox adaptation. However, their combined prognostic value remains unclear.

We retrospectively analyzed 138 resected cases of PC. Stromal TIL density was assessed on hematoxylin-eosin (H&E) sections, and tumor PRDX4 expression was evaluated by immunohistochemistry. Both markers were dichotomized into high and low groups using ROC-derived thresholds. Patients were further classified into four integrated subgroups: TIL-high/PRDX4-low (TH-PL), TIL-high/PRDX4-high (TH-PH), TIL-low/PRDX4-low (TL-PL), and TIL-low/PRDX4-high (TL-PH). Associations with clinicopathological features and disease-specific survival (DSS) were analyzed.

High TIL density was associated with less advanced pathological stage and significantly improved DSS, whereas high PRDX4 expression correlated with lymphovascular and perineural invasion as well as advanced stage. An inverse association between TILs and PRDX4 was observed. Integrated subgroup analysis revealed distinct prognostic patterns: the TL-PH subgroup showed the poorest DSS, whereas the TH-PL subgroup demonstrated the most favorable outcomes. In multivariable Cox models, the TL-PH subgroup remained an independent adverse prognostic factor for both 3- and 5-year DSS, while the TH-PL subgroup showed a protective effect, particularly at 3 years.

Stromal TILs and PRDX4 appear to capture complementary immune and redox features of PC. Their combined assessment may improve prognostic stratification and help to identify a potential redox-associated, immune-excluded subgroup with particularly poor outcomes.

论文信息

作者
Liu Y、Han J、Shioya A、Jiao W、Okuro M、Ito T、Yamada S
第一作者单位
Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, 920-0293, Japan.Japan
通讯作者单位
Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, 920-0293, Japan. sohsuke@kanazawa-med.ac.jp.Japan
期刊
Diagnostic pathology2026 Apr 16
原文标识
PubMed 41992245 · DOI 10.1186/s13000-026-01786-8