Sherry Christopher, Dadgar Neda, Park Hyun, Knotts Chelsea, Grayhack Erin, Blodgett Rose, Xiao Kunhong, Omstead Ashten N, Donnenberg Albert D, Bartlett David L, Donnenberg Vera, Goel Ajay, Zaidi Ali H, Wagner Patrick L
Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA.
Translational Hematology and Medical Oncology Department, Cleveland Clinic, Cleveland, OH 44195, USA.
Microorganisms. 2025 Jul 11;13(7):1644. doi: 10.3390/microorganisms13071644.
Emerging evidence highlights the role of the tumor microbiome, including (Fn), in a wide range of gastrointestinal cancers. Fn purportedly contributes to tumorigenesis by activating oncogenic pathways and modulating immune responses. Although the prevalence and impact of Fn has been extensively studied in colorectal cancer, no previous systematic or in situ studies have been performed in appendiceal cancer (AC). The aim of this study was to evaluate the prevalence and association of Fn density in AC with clinical factors and oncologic outcomes. Archival tissue from 54 patients with AC was assessed for Fn density using RNA in situ hybridization. Clinicopathological variables were obtained for each case through electronic medical record review, and the immune microenvironment was characterized in each case using immunohistochemistry to quantify CD3+ and CD8+ T lymphocytes and M1-/M2-like tumor-associated macrophages. In AC, Fn density was associated with patient age, tumor grade, and histologic subtype. Fn was negatively associated with CD3+ and CD8+ T lymphocytes and positively associated with M2-like TAMs in low-grade AC. Interestingly, tumor Fn content was associated with better overall and progression-free survival, even when controlling for tumor grade. In this exploratory study, we found that Fn is prevalent in AC. Fn is associated with a number of clinical, pathologic, immunologic, and prognostic variables in AC that are distinct from the corresponding observed associations in colorectal cancer. Further research is warranted to validate these findings and explore the mechanistic contributions of Fn to AC pathogenesis or immune response.
新出现的证据凸显了肿瘤微生物群，包括具核梭杆菌（Fn），在多种胃肠道癌症中的作用。据称，Fn通过激活致癌途径和调节免疫反应促进肿瘤发生。尽管Fn在结直肠癌中的发生率和影响已得到广泛研究，但此前尚未对阑尾癌（AC）进行过系统或原位研究。本研究的目的是评估AC中Fn密度与临床因素及肿瘤学结局的相关性。使用RNA原位杂交评估了54例AC患者存档组织中的Fn密度。通过电子病历回顾获取每个病例的临床病理变量，并使用免疫组织化学对每个病例的免疫微环境进行特征分析，以量化CD3 +和CD8 + T淋巴细胞以及M1型/M2型肿瘤相关巨噬细胞。在AC中，Fn密度与患者年龄、肿瘤分级和组织学亚型相关。在低级别AC中，Fn与CD3 +和CD8 + T淋巴细胞呈负相关，与M2型肿瘤相关巨噬细胞呈正相关。有趣的是，即使在控制肿瘤分级的情况下，肿瘤Fn含量也与更好的总生存期和无进展生存期相关。在这项探索性研究中，我们发现Fn在AC中普遍存在。Fn与AC中的许多临床、病理、免疫和预后变量相关，这些变量与在结直肠癌中观察到的确切关联不同。有必要进行进一步研究以验证这些发现，并探索Fn对AC发病机制或免疫反应的机制性作用。
