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Parvimonas micra as a putative non-invasive faecal biomarker for colorectal cancer.

Author(s): Löwenmark T, Löfgren-Burström A, Zingmark C, Eklöf V, Dahlberg M, Wai SN, Larsson P, Ljuslinder I, Edin S, Palmqvist R

Publication: Sci Rep, 2020, Vol. 10, Page 15250

PubMed ID: 32943695 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   This study investigated the relative abundance of P. micra in fecal specimens of CRC patients compared to patients with dysplasia and healthy controls. Sensitivity and specificity of positive microbial tests for the detection of CRC were also examined. Fecal specimens were collected from patients undergoing colonoscopy for gastrointestinal symptoms indicative of large bowel disease [visible blood in feces and/or positive fecal hemoglobin (F-Hb)] from two study cohorts between 2008 and 2014. After pathological analysis, 38 were diagnosed with CRC (18 female, 20 male) and 128 with low or high grade dysplasia (55 female, 73 male) in the first cohort and 238 CRC patients (95 female, 143 male) were identified in the second cohort. Fecal specimens were also collected from 94 age and gender-matched controls. Specimens were collected by the patients at their home in stool collection tubes containing 5 mL of RNAlater, stored for up to 7 days at room temperature, transported to the laboratory, centrifuged at 2000 rpm for 20 min, and stored at -80°C. DNA was extracted using the QIAamp PowerFecal DNA Kit. P. micra, F. nucleatum, and clbA+ bacteria were detected using the Quant-Studio 6 Flex Real-Time PCR System (positive cut-off value = CT≤38). Levels of P. micra, F. nucleatum, and clbA+ bacteria were presented as a relative quantification of the total microbial content using the 16S rRNA gene as reference.

   Summary of Findings:

   P. micra, F. nucleatum, and clbA+ bacteria were significantly more abundant in fecal specimens from CRC patients in the first cohort compared to patients with dysplasia (P<0.001, P<0.001, and P=0.01; respectively) and healthy controls (P<0.001, P<0.001, and P=0.07; respectively), but no significant difference was found between dysplasia patients and controls (P=0.286). Results were confirmed for patients in the second cohort. Sensitivity and specificity of a positive P. micra real-time qRT-PCR test for the detection of colon cancer in the first cohort were 60.5% and 56.7%, respectively, and 87.3% and 92.6% for the second cohort, respectively. Sensitivity and specificity of a positive F. nucleatum result for detection of CRC were 61.1% and 81.4% for the first cohort and 60.0% and 79.1% in the second cohort. Similarly, sensitivity and specificity of clbA+ bacteria for the detection of CRC in the first cohort were 56.8% and 77.0%, respectively, and 46.6% and 67.7% in the second cohort, respectively. The addition of a positive F-Hb test in the first cohort increased the sensitivity of the test for P. micra to 85.7%, for F. nucleatum to 92.6%, and to 95.7% for clbA+ bacteria while decreasing the specificity to 75.0%, 64.9%, and 48.6%, respectively.

   Biospecimens

   • Bodily Fluid - Feces

   Preservative Types

   • Frozen

   Diagnoses:

   • Neoplastic - Carcinoma
   • Normal

   Platform:

   Analyte	Technology Platform
   RNA	Real-time qRT-PCR

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Diagnosis/ patient condition	Normal Colorectal cancer Dysplasia
   Real-time qRT-PCR Specific	Targeted nucleic acid	16s rRNA

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