Exome and Tissue-Associated Microbiota as Predictive Markers of Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer.

The clinical and pathological responses to multimodal neoadjuvant therapy in locally advanced rectal cancers (LARCs) remain unpredictable, and robust biomarkers are still lacking. Recent studies have shown that tumors present somatic molecular alterations related to better treatment response, and it is also clear that tumor-associated bacteria are modulators of chemotherapy and immunotherapy efficacy, therefore having implications for long-term survivorship and a good potential as the biomarkers of outcome. Here, we performed whole exome sequencing and 16S ribosomal RNA (rRNA) amplicon sequencing from 44 pre-treatment LARC biopsies from Argentinian and Brazilian patients, treated with neoadjuvant chemoradiotherapy or total neoadjuvant treatment, searching for predictive biomarkers of response (responders, n = 17; non-responders, n = 27). In general, the somatic landscape of LARC was not capable to predict a response; however, a significant enrichment in mutational signature SBS5 was observed in non-responders (p = 0.0021), as well as the co-occurrence of APC and FAT4 mutations (p < 0.05). Microbiota studies revealed a similar alpha and beta diversity of bacteria between response groups. Yet, the linear discriminant analysis (LDA) of effect size indicated an enrichment of Hungatella, Flavonifractor, and Methanosphaera (LDA score ≥3) in the pre-treatment biopsies of responders, while non-responders had a higher abundance of Enhydrobacter, Paraprevotella (LDA score ≥3) and Finegoldia (LDA score ≥4). Altogether, the evaluation of these biomarkers in pre-treatment biopsies could eventually predict a neoadjuvant treatment response, while in post-treatment samples, it could help in guiding non-operative treatment strategies.

Evaluation of Bacteria and Fungi DNA Abundance in Human Tissues.

Whereas targeted and shotgun sequencing approaches are both powerful in allowing the study of tissue-associated microbiota, the human: microorganism abundance ratios in tissues of interest will ultimately determine the most suitable sequencing approach. In addition, it is possible that the knowledge of the relative abundance of bacteria and fungi during a treatment course or in pathological conditions can be relevant in many medical conditions. Here, we present a qPCR-targeted approach to determine the absolute and relative amounts of bacteria and fungi and demonstrate their relative DNA abundance in nine different human tissue types for a total of 87 samples. In these tissues, fungi genomes are more abundant in stool and skin samples but have much lower levels in other tissues. Bacteria genomes prevail in stool, skin, oral swabs, saliva, and gastric fluids. These findings were confirmed by shotgun sequencing for stool and gastric fluids. This approach may contribute to a more comprehensive view of the human microbiota in targeted studies for assessing the abundance levels of microorganisms during disease treatment/progression and to indicate the most informative methods for studying microbial composition (shotgun versus targeted sequencing) for various samples types.

Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings

A retrospective multicentre study of cystic lesions and odontogenic tumours in older people.

OBJECTIVE: The aim of this study was to investigate the frequency and some characteristics of odontogenic tumours, odontogenic cysts and non-odontogenic cysts in an elderly population (≥60 years). BACKGROUND: Few studies describe the distribution of oral lesions in older people. MATERIALS AND METHODS: A retrospective descriptive cross-sectional study was performed. Biopsy records were obtained from the archives of four Brazilian referral centres between 2000 and 2016. Data such as gender, age, anatomical location, symptomatology and histopathological diagnosis were collected and categorised. Statistical analyses were performed adopting a P-value of ≤.05 and a 95% confidence interval. RESULTS: A total of 7259 biopsy records of elderly participants were analysed; 642 cases were cystic lesions and odontogenic tumours, 491 of which being classified as odontogenic cysts (76.5%), 75 as odontogenic tumours (11.7%) and 76 as non-odontogenic cysts (11.8%). The most frequent lesions in each group were radicular cyst (n = 268), ameloblastoma (n = 51) and salivary duct cyst (n = 21), respectively. Overall, women were more affected (n = 351, mean age: 68 years). Intraosseous lesions were more common in the mandible (n = 342), and soft tissue cysts occurred more in the lip (n = 13). CONCLUSION: Odontogenic cysts were relatively common, whereas odontogenic tumours and non-odontogenic cysts were rarer among the older people studied in the present investigation.