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Stage-dependent and heterogeneous tumor association of Fusobacterium nucleatum in Romanian patients with colon adenocarcinoma
Simona Turcu, Konstantina-Lida Prasoula, Evangelia Legaki, Florin Andrei Grama, Draga-Maria Mandi, Adrian Bordea, Catalin Andrei Dutei, Maria Gazouli
Simona Turcu, Department of Surgery, Carol Davila University of Medicine and Pharmacy, Fundeni Clinical Institute, Bucharest 050474, Romania
Konstantina-Lida Prasoula, Maria Gazouli, Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, Athens 11527, Attikí, Greece
Evangelia Legaki, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
Florin Andrei Grama, Department of Surgery, “Carol Davila” University of Medicine and Pharmacy, Bucharest 050474, Romania
Draga-Maria Mandi, Department of Surgery, Colțea Clinical Hospital, Bucharest 030167, București, Romania
Adrian Bordea, Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Bucuresti, Romania
Catalin Andrei Dutei, Department of Gastroenterology, Fundeni Clinical Institute, Bucharest 022258, Romania
Co-corresponding authors: Florin Andrei Grama and Maria Gazouli.
Author contributions: Turcu S contributed to the conceptualization and design of the study; Turcu S, Prasoula KL, and Legaki E performed sample processing, data acquisition, and molecular analyses; Grama FA, Mandi DM, Bordea A, and Dutei CA contributed to patient recruitment, clinical data collection, and literature review; Gazouli M provided critical scientific supervision and contributed to study coordination and manuscript revision. All authors contributed to the drafting and critical revision of the manuscript and approved the final version for submission. Gazouli M and Grama FA served as co-corresponding authors and contributed equally to the study. Both played essential and complementary roles in the overall study conception and design, scientific supervision, data interpretation, and manuscript preparation, and share equal responsibility for the integrity and communication of the work.
AI contribution statement: ChatGPT was used as AI tool for grammar and language polishing, and rephrasing.
Supported by the University of Medicine and Pharmacy ‘Carol Davila’, No. 10S10/08.05.2025.
Institutional review board statement: This study was approved by the Ethics Committee at Colțea Clinical Hospital.
Informed consent statement: All study participants provided written consent before study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: No additional data are available.
Corresponding author: Maria Gazouli, PhD, Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, No. 176 Michalakopoulou, Athens 11527, Greece.
mgazouli@med.uoa.gr
Received: January 12, 2026
Revised: January 25, 2026
Accepted: February 25, 2026
Published online: June 15, 2026
Processing time: 150 Days and 18.6 Hours
BACKGROUND
Colorectal cancer remains a major cause of cancer-related mortality worldwide, with a particularly high burden in Eastern Europe. Increasing evidence implicates the gut microbiome, especially Fusobacterium nucleatum (F. nucleatum), in colorectal carcinogenesis; however, tumor-associated microbial patterns are heterogeneous and population-specific. To date, colorectal cancer microbiome data from Romanian patients are lacking. We hypothesized that F. nucleatum tumor association in Romanian patients is heterogeneous and varies according to tumor-related biological context rather than showing uniform enrichment.
AIM
To investigate tumor-associated distribution patterns of F. nucleatum in Romanian patients with colon adenocarcinoma.
METHODS
This prospective observational pilot study included 15 patients undergoing curative-intent surgery for colon adenocarcinoma at a tertiary referral center. Paired tumor and adjacent non-tumoral colonic tissues were analyzed using quantitative real-time polymerase chain reaction for F. nucleatum DNA (FS17 assay) and microRNA-21 (miR-21) expression. Molecular data were integrated with tumor stage, nodal status, inflammatory markers, and clinicopathological variables using paired comparisons and exploratory statistical analyses.
RESULTS
F. nucleatum detection showed marked interindividual variability across paired samples. Tumor-predominant detection was observed in slightly more than half of the cases, without a significant overall difference between tumor and adjacent tissue (P = 0.82). FS17 tumor Ct values were significantly lower in T2 tumors compared with T3-T4 tumors (24.63 ± 1.45 vs 28.53 ± 3.85, P = 0.01), indicating higher bacterial signal in earlier-stage disease. No statistically significant associations were observed with nodal status, demographic variables, or surgical characteristics. miR-21 expression was increased in tumor tissue, but did not correlate with F. nucleatum detection.
CONCLUSION
Tumor association of F. nucleatum in colon adenocarcinoma is heterogeneous and stage-dependent rather than uniform. This pilot study provides the first paired tissue-based microbiome data from Romanian patients and establishes a foundation for larger, longitudinal investigations.
Core Tip: This pilot study presents the first paired tumor-adjacent tissue analysis of Fusobacterium nucleatum in Romanian patients with colon adenocarcinoma. Using quantitative real-time polymerase chain reaction, we show that tumor-associated Fusobacterium nucleatum signals are heterogeneous and stage-dependent rather than uniformly enriched. Higher bacterial signal was observed in earlier T-stage tumors, while no consistent associations were identified with demographic, surgical, or microRNA-21 expression profiles. These findings provide initial population-specific insight into tumor-microbe interactions and establish a foundation for larger, longitudinal studies evaluating the clinical relevance of colorectal cancer-associated microbiota.
