Prognostic Value of Fusobacterium nucleatum after Abdominoperineal Resection for Anal Squamous Cell Carcinoma

Abstract

Main prognostic factors of anal squamous cell carcinoma (ASCC) are tumor size, differentiation, lymph node involvement, and male gender. However, they are insufficient to predict relapses after exclusive radiotherapy (RT) or chemoradiotherapy (CRT). Fusobacterium nucleatum has been associated with poor prognosis in several digestive cancers. In this study, we assessed the association between intratumoral F. nucleatum load and clinico-pathological features, relapse, and survival in patients with ASCC who underwent abdominoperineal resection (APR) after RT/CRT. We retrospectively analyzed surgical samples from a cohort of 166 patients with ASCC who underwent APR. F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. We associated F. nucleatum load with classical clinicopathological features, overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) using Cox regression univariate and multivariate analyses. Tumors harboring high loads of F. nucleatum (highest tercile) showed longer OS and DFS (median: not reached vs. 50.1 months, p = 0.01, and median: not reached vs. 18.3 months, p = 0.007, respectively). High F. nucleatum load was a predictor of longer OS (HR = 0.55, p = 0.04) and DFS (HR = 0.50, p = 0.02) in multivariate analysis. High F. nucleatum load is an independent favorable prognostic factor in patients with ASCC who underwent APR.

Utility ofCYP2D6copy number variants as prognostic biomarker in localized anal squamous cell carcinoma

“…defined that mutations in PIK3CA were associated with worst OS in recurrent patients after an abdominoperineal resection. A recent study established that high levels of Fusobacterium nucleatum were associated with better OS and DFS in patients who suffered a progression and underwent abdominoperineal resection 36 . In a previous work, we identified that presenting a high or moderate impact of genetic variants in BRCA2 , ZNF750 , FAM208B , ZNF599 , and ZC3H13 genes was related to DFS in localized ASCC 12 .…”

“…A recent study established that high levels of Fusobacterium nucleatum were associated with better OS and DFS in patients who suffered a progression and underwent abdominoperineal resection. 36 In a previous work, we identified that presenting a high or moderate impact of genetic variants in BRCA2, ZNF750, FAM208B, ZNF599, and ZC3H13 genes was related to DFS in localized ASCC. 12 This is the first study in localized ASCC that associated CNVs with DFS.…”

Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy

“…250 Similarly, for anal squamous cell carcinoma patients undergoing abdominal perineal resection after radiotherapy/chemoradiotherapy with high levels of F. nucleatum had longer overall survival and disease-free survival. 251 Thus, intratumoral microbiota can be used as biomarkers for diagnosis and prognosis to provide potential treatment guidance for patients with different risk stratifications. Until now, most research on intratumoral microbes has been based on surgically removed samples, but not all cases present the opportunity to operate.…”

The microbiome as a biomarker of anal precancerous lesions in people with HIV

“…Nevertheless, data directly linking the microbiome with anal cancer are currently scarce. A prospective study by Elnaggar et al [27 ▪ ] described changes in beta diversity composition in patients with localized anal squamous cell carcinoma (ASCC) An association was found between a higher intratumoral load of Fusobacterium nucleatum and survival outcomes in patients undergoing surgery for ASCC, suggesting an immune modulatory effect linked to the tumor cell lineage [28].…”

“…The connection between the microbiome and HPV has recently become a focal point of scientific research. Numerous studies have attempted to decipher the impact of the microbiome on HPV infection, persistence, and progression to cervical dysplasia and cancer in women (Table 1) [6,7,10,16,[18][19][20][21][22][25][26][27][28][29][30][31][32].…”