Diagnostic and prognostic significance of circulating secreted frizzled-related protein 5 in colorectal cancer.

BACKGROUND: Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) METHODS: Plasma cSFRP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64). RESULTS: Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II-III CRC (univariate: HR 1.82, 95% CI: 1.02-3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12-4.88, p = 0.015). CONCLUSION: This study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II-III disease.

Identification of consensus head and neck cancer-associated microbiota signatures: a systematic review and meta-analysis of 16S rRNA and The Cancer Microbiome Atlas datasets.

Introduction. Multiple reports have attempted to describe the tumour microbiota in head and neck cancer (HNSC).Gap statement. However, these have failed to produce a consistent microbiota signature, which may undermine understanding the importance of bacterial-mediated effects in HNSC.Aim. The aim of this study is to consolidate these datasets and identify a consensus microbiota signature in HNSC.Methodology. We analysed 12 published HNSC 16S rRNA microbial datasets collected from cancer, cancer-adjacent and non-cancer tissues to generate a consensus microbiota signature. These signatures were then validated using The Cancer Microbiome Atlas (TCMA) database and correlated with the tumour microenvironment phenotypes and patient's clinical outcome.Results. We identified a consensus microbial signature at the genus level to differentiate between HNSC sample types, with cancer and cancer-adjacent tissues sharing more similarity than non-cancer tissues. Univariate analysis on 16S rRNA datasets identified significant differences in the abundance of 34 bacterial genera among the tissue types. Paired cancer and cancer-adjacent tissue analyses in 16S rRNA and TCMA datasets identified increased abundance in Fusobacterium in cancer tissues and decreased abundance of Atopobium, Rothia and Actinomyces in cancer-adjacent tissues. Furthermore, these bacteria were associated with different tumour microenvironment phenotypes. Notably, high Fusobacterium signature was associated with high neutrophil (r=0.37, P<0.0001), angiogenesis (r=0.38, P<0.0001) and granulocyte signatures (r=0.38, P<0.0001) and better overall patient survival [continuous: HR 0.8482, 95 % confidence interval (CI) 0.7758-0.9273, P=0.0003].Conclusion. Our meta-analysis demonstrates a consensus microbiota signature for HNSC, highlighting its potential importance in this disease.