Dataset Information

Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls.

ABSTRACT: Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.

SUBMITTER: Mutignani M

PROVIDER: S-EPMC8699505 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls.

Mutignani Massimiliano M Penagini Roberto R Gargari Giorgio G Guglielmetti Simone S Cintolo Marcello M Airoldi Aldo A Leone Pierfrancesco P Carnevali Pietro P Ciafardini Clorinda C Petrocelli Giulio G Mascaretti Federica F Oreggia Barbara B Dioscoridi Lorenzo L Cavalcoli Federica F Primignani Massimo M Pugliese Francesco F Bertuccio Paola P Soru Pietro P Magistro Carmelo C Ferrari Giovanni G Speciani Michela C MC Bonato Giulia G Bini Marta M Cantù Paolo P Caprioli Flavio F Vangeli Marcello M Forti Edoardo E Mazza Stefano S Tosetti Giulia G Bonzi Rossella R Vecchi Maurizio M La Vecchia Carlo C Rossi Marta M

Cancers 20211218 24

Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied condit ...[more]

PMID: 34944982

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Project description:BackgroundHereditary haemorrhagic telangiectasia (HHT) is inherited as an autosomal dominant trait, affects ~1 in 5,000, and causes multi-systemic vascular lesions and life-limiting complications. Life expectancy is surprisingly good, particularly for patients over 60ys. We hypothesised that individuals with HHT may be protected against life-limiting cancers.MethodsTo compare specific cancer rates in HHT patients and controls, we developed a questionnaire capturing data on multiple relatives per respondent, powered to detect differences in the four most common solid non skin cancers (breast, colorectal, lung and prostate), each associated with significant mortality. Blinded to cancer responses, reports of HHT-specific features allowed assignment of participants and relatives as HHT-subjects, unknowns, or controls. Logistic and quadratic regressions were used to compare rates of specific cancer types between HHT subjects and controls.Results1,307 participants completed the questionnaire including 1,007 HHT-subjects and 142 controls. The rigorous HHT diagnostic algorithm meant that 158 (12%) completed datasets were not assignable either to HHT or control status. For cancers predominantly recognised as primary cancers, the rates in the controls generally matched age-standardised rates for the general population. HHT subjects recruited through the survey had similar demographics to controls, although the HHT group reported a significantly greater smoking habit. Combining data of participants and uniquely-reported relatives resulted in an HHT-arm of 2,161 (58% female), and control-arm of 2,817 (52% female), with median ages of 66ys [IQR 53-77] and 77ys [IQR 65-82] respectively. In both crude and age-adjusted regression, lung cancers were significantly less frequent in the HHT arm than controls (age-adjusted odds ratio 0.48 [0.30, 0.70], p = 0.0012). Breast cancer prevalence was higher in HHT than controls (age-adjusted OR 1.52 [1.07, 2.14], p = 0.018). Overall, prostate and colorectal cancer rates were equivalent, but the pattern of colorectal cancer was modified, with a higher prevalence in younger HHT patients than controls.ConclusionsThese preliminary survey data suggest clinically significant differences in the rates of lung, breast and colorectal cancer in HHT patients compared to controls. For rare diseases in which longitudinal studies take decades to recruit equivalent datasets, this type of methodology provides a good first-step method for data collection.

Project description:BackgroundCell-free DNA (cfDNA) profiling is increasingly used to guide cancer care, yet mutations are not always identified. The ability to detect somatic mutations in plasma depends on both assay sensitivity and the fraction of circulating DNA in plasma that is tumor-derived (i.e., cfDNA tumor fraction). We hypothesized that cfDNA tumor fraction could inform the interpretation of negative cfDNA results and guide the choice of subsequent assays of greater genomic breadth or depth.MethodsPlasma samples collected from 118 metastatic cancer patients were analyzed with cf-IMPACT, a modified version of the FDA-authorized MSK-IMPACT tumor test that can detect genomic alterations in 410 cancer-associated genes. Shallow whole genome sequencing (sWGS) was also performed in the same samples to estimate cfDNA tumor fraction based on genome-wide copy number alterations using z-score statistics. Plasma samples with no somatic alterations detected by cf-IMPACT were triaged based on sWGS-estimated tumor fraction for analysis with either a less comprehensive but more sensitive assay (MSK-ACCESS) or broader whole exome sequencing (WES).ResultscfDNA profiling using cf-IMPACT identified somatic mutations in 55/76 (72%) patients for whom MSK-IMPACT tumor profiling data were available. A significantly higher concordance of mutational profiles and tumor mutational burden (TMB) was observed between plasma and tumor profiling for plasma samples with a high tumor fraction (z-score≥5). In the 42 patients from whom tumor data was not available, cf-IMPACT identified mutations in 16/42 (38%). In total, cf-IMPACT analysis of plasma revealed mutations in 71/118 (60%) patients, with clinically actionable alterations identified in 30 (25%), including therapeutic targets of FDA-approved drugs. Of the 47 samples without alterations detected and low tumor fraction (z-score<5), 29 had sufficient material to be re-analyzed using a less comprehensive but more sensitive assay, MSK-ACCESS, which revealed somatic mutations in 14/29 (48%). Conversely, 5 patients without alterations detected by cf-IMPACT and with high tumor fraction (z-score≥5) were analyzed by WES, which identified mutational signatures and alterations in potential oncogenic drivers not covered by the cf-IMPACT panel. Overall, we identified mutations in 90/118 (76%) patients in the entire cohort using the three complementary plasma profiling approaches.ConclusionscfDNA tumor fraction can inform the interpretation of negative cfDNA results and guide the selection of subsequent sequencing platforms that are most likely to identify clinically-relevant genomic alterations.

Dataset Information

Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls.

Publications

Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls.

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