Institute for Virology, Saarland University Medical Center, Saarland University, Kirrberger Str. Building 47, 66421, Homburg, Germany.
Current Address: Leibniz-Institute for New Materials (INM), Campus D2.2, 66123, Saarbrücken, Germany.
Sci Rep. 2024 Sep 27;14(1):22050. doi: 10.1038/s41598-024-70855-z.
PeCa is a rare entity with rising incidence rates due to increased infections with human papillomaviruses (HPV). The distinct subtypes of PeCa with an individual pathogenesis demand biomarkers for a precise patient risk assessment regarding disease progression and therapeutic susceptibility. We recently identified promising candidates associated with an HPV-instructed tumor microenvironment (TME) using HPV-positive PeCa cell lines and tissue microarrays (TMA). The capacity of HPV + p63 + PeCa cells to release neutrophil-attracting CXCL-8 provided a molecular link explaining the infiltration of CD15 + myeloid cells in PeCa specimens. The candidate biomarkers HPV, p63, CD15, DKK1, and CD147 linked a tumor-promoting TME with a higher TNM classification reflecting more aggressive and metastasizing cancers. Based on immune-reactive scores (IRS) from TMA staining for these biomarkers, we calculated correlations and conducted association analyses to assess the degree of relationship between all biomarkers. We then conducted Kaplan-Meier survival estimates and Cox regression analyses to delineate the impact on PeCa patient survival. There is a notable predictive potential regarding the survival of patients with biomarker profiles beyond the potency of the individual biomarker. From all candidate biomarkers and biomarker profiles, the combination of CD147 and infiltrating CD15 + cells linked to an active HPV-driven transformation displayed cancer-immune dynamics with dismal prognosis for patients. After deciphering relevant interdependencies, the HPV + CD147 + CD15 + status was the most potent profile predicting metastasis-free survival of PeCa patients. The results of this report underscore the need for analysis of the TME and the development of multi-parameter composite scores that reflect fundamental cancer-immune relationships to tailor therapeutic interventions based on actual cancer immune dynamics.
PeCa 是一种罕见的实体瘤，由于人乳头瘤病毒（HPV）感染的增加，其发病率不断上升。PeCa 的不同亚型具有个体发病机制，需要生物标志物来精确评估疾病进展和治疗敏感性的患者风险。我们最近使用 HPV 阳性 PeCa 细胞系和组织微阵列（TMA）发现了与 HPV 指导的肿瘤微环境（TME）相关的有前途的候选标志物。HPV + p63 + PeCa 细胞释放吸引中性粒细胞的 CXCL-8 的能力提供了一个分子联系，解释了 PeCa 标本中 CD15 + 髓样细胞的浸润。候选生物标志物 HPV、p63、CD15、DKK1 和 CD147 将促进肿瘤的 TME 与反映更具侵袭性和转移性癌症的更高 TNM 分类联系起来。基于这些生物标志物的 TMA 染色免疫反应评分（IRS），我们计算了相关性并进行了关联分析，以评估所有生物标志物之间关系的程度。然后，我们进行了 Kaplan-Meier 生存估计和 Cox 回归分析，以描绘对 PeCa 患者生存的影响。在考虑了生物标志物谱的生存预测潜力后，我们发现这种预测潜力超过了单个生物标志物的作用。在所有候选生物标志物和生物标志物谱中，与活跃 HPV 驱动的转化相关的 CD147 和浸润性 CD15 + 细胞的组合显示出癌症免疫动力学，患者预后不佳。在破译相关的相互依存关系后，HPV + CD147 + CD15 + 状态是预测 PeCa 患者无转移生存的最有效预测因子。本报告的结果强调了分析 TME 和开发反映基本癌症-免疫关系的多参数综合评分的必要性，以便根据实际癌症免疫动力学调整治疗干预措施。
