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伴有显著炎症的前列腺癌中的人类疱疹病毒基因型和免疫基因表达谱

Human Herpes Virus Genotype and Immunological Gene Expression Profile in Prostate Cancer with Prominent Inflammation.

作者信息

Todorova Elena, Kavrakova Anita, Derimachkovski Goran, Georgieva Bilyana, Odzhakov Feodor, Bachurska Svitlana, Terziev Ivan, Boyadzhieva Maria-Elena, Valkov Trifon, Popov Elenko, Slavov Chavdar, Tourtourikov Ivan, Mitev Vanyo, Todorova Albena

机构信息

Department of Medical Chemistry and Biochemistry, MU-Sofia, 1431 Sofia, Bulgaria.

Genetic and Medico-Diagnostic Laboratory "Genica", 1463 Sofia, Bulgaria.

出版信息

Int J Mol Sci. 2025 May 21;26(10):4945. doi: 10.3390/ijms26104945.

Abstract

We aim to investigate the role of the family () in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 "tru-cut" biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the "tru-cut" biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ ≈ 20.3, df = 1, < 0.0001; Fisher's exact test, < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80-15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression.

摘要

我们旨在研究[具体病毒家族名称]在前列腺癌(PCa)发病及进展中的作用,并剖析局部PCa的免疫状态。使用实时定量聚合酶链反应(qPCR)和组织学检查,对116例“粗针穿刺”活检样本(58例PCa和58例良性前列腺增生[BPH])以及49例PCa的福尔马林固定石蜡包埋(FFPE)样本进行了分析。在11.5%的“粗针穿刺”活检样本中检测到巨细胞病毒(CMV)、EB病毒(EBV)、人疱疹病毒6型(HHV6)和人疱疹病毒7型(HHV7)感染(BPH组为25.9%,PCa组为6.9%)。在福尔马林固定石蜡包埋(FFPE)样本中,69.4%的患者检测到感染,其中EBV(47%)、HHV6(38%)、HHV7(41%)、CMV(2.9%)、单纯疱疹病毒2型(HSV2)(2.9%)和水痘-带状疱疹病毒(VZV)(5.8%)的感染率各不相同。在HHV感染的PCa病例中,组织病理学特征包括肿瘤内淋巴细胞浸润伴纤维化和坏死、导管周围慢性炎症反应以及伴有脓肿和坏死灶的肉芽肿性病变,还有炎症浸润、慢性淋巴结炎、前列腺上皮内萎缩(PIA)和高级别前列腺上皮内瘤变(HGPIN)。大多数HHV感染的PCa患者主要被归类为G3/G4/G5级肿瘤,表现为神经周围、血管周围和淋巴管浸润、精囊侵犯、精囊淀粉样变和淋巴结转移。统计分析表明HHV感染与PCa之间存在显著关联(χ²≈20.3,自由度=1,P<0.0001;Fisher精确检验,P<0.0001),优势比为6.50(95%置信区间:2.80 - 15.12)。这些发现表明,长期HHV感染可能由于炎症导致复杂且可能改变的免疫PCa肿瘤环境。这可能作为侵袭性疾病进展的预测指标。

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