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Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer
Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis. Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two i...
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| Published in: | Clinical cancer research 2017-04, Vol.23 (8), p.2061-2070 |
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| container_title | Clinical cancer research |
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| creator | Liang, Qiaoyi Chiu, Jonathan Chen, Yingxuan Huang, Yanqin Higashimori, Akira Fang, Jingyuan Brim, Hassan Ashktorab, Hassan Ng, Siew Chien Ng, Simon Siu Man Zheng, Shu Chan, Francis Ka Leung Sung, Joseph Jao Yiu Yu, Jun |
| description | Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.
Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.
Candidates identified by metagenome sequencing, including
(
),
(
),
(
),
(
), and one undefined species (labeled as
), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (
= 0.801-0.934, all
< 0.0001).
was significantly more abundant in colorectal cancer than controls (
< 0.0001), with AUROC of 0.868 (
< 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity,
discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (
+
+
-
) showed an improved diagnostic ability compared with
alone (AUROC = 0.886,
< 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of
alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.
Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.
. |
| doi_str_mv | 10.1158/1078-0432.ccr-16-1599 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1891881480</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1835353094</sourcerecordid><originalsourceid>FETCH-LOGICAL-c535t-f457871ee07e32553bd37476814371d7146bf6c701073a67408209d76009fbec3</originalsourceid><addsrcrecordid>eNqNkU1LxDAQhosofv8EpeDFS9dM833U-gmLgug5pNmpdO02mnQX_Pem7OrBk6cJwzPvZN43y06ATAC4ugAiVUEYLSfOhQJEAVzrrWwfOJcFLQXfTu8fZi87iHFOCDAgbDfbK6XQUmuxn73eorNdfmXdgKG1-aUbchvzR7_C1G39woZ3DDFvfEjNvu1XNrYrzK9b-9b72MbcN3nlOx_QDUmosr3DcJTtNLaLeLyph2nPzUt1X0yf7h6qy2nhOOVD0TAulQREIpGWnNN6RiWTQgGjEmYSmKgb4SRJh1ArJCOqJHomBSG6qdHRw-x8rfsR_OcS42AWbXTYdbZHv4wGlAaV1BT5B0rTnyjRLKFnf9C5X4Y-HWJAK8pAMqoTxdeUCz7GgI35CG2y68sAMWNEZrTfjPabqno2IMwYUZo73agv6wXOfqd-MqHfoHGJmQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983417439</pqid></control><display><type>article</type><title>Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer</title><source>Science Journals (Open access)</source><creator>Liang, Qiaoyi ; Chiu, Jonathan ; Chen, Yingxuan ; Huang, Yanqin ; Higashimori, Akira ; Fang, Jingyuan ; Brim, Hassan ; Ashktorab, Hassan ; Ng, Siew Chien ; Ng, Simon Siu Man ; Zheng, Shu ; Chan, Francis Ka Leung ; Sung, Joseph Jao Yiu ; Yu, Jun</creator><creatorcontrib>Liang, Qiaoyi ; Chiu, Jonathan ; Chen, Yingxuan ; Huang, Yanqin ; Higashimori, Akira ; Fang, Jingyuan ; Brim, Hassan ; Ashktorab, Hassan ; Ng, Siew Chien ; Ng, Simon Siu Man ; Zheng, Shu ; Chan, Francis Ka Leung ; Sung, Joseph Jao Yiu ; Yu, Jun</creatorcontrib><description>Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.
Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.
Candidates identified by metagenome sequencing, including
(
),
(
),
(
),
(
), and one undefined species (labeled as
), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (
= 0.801-0.934, all
< 0.0001).
was significantly more abundant in colorectal cancer than controls (
< 0.0001), with AUROC of 0.868 (
< 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity,
discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (
+
+
-
) showed an improved diagnostic ability compared with
alone (AUROC = 0.886,
< 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of
alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.
Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.ccr-16-1599</identifier><identifier>PMID: 27697996</identifier><language>eng</language><publisher>United States: American Association for Cancer Research Inc</publisher><subject>Adult ; Aged ; Area Under Curve ; Bacteria ; Bacteroides ; Biomarkers ; Biomarkers, Tumor - analysis ; Cancer ; Candidates ; Clostridium ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - diagnosis ; Colorectal Neoplasms - microbiology ; Diagnosis ; Diagnostic systems ; Experimental design ; Feces ; Feces - microbiology ; Female ; Fusobacterium nucleatum ; Gastrointestinal Microbiome ; Humans ; Intestinal microflora ; Male ; Microbiota ; Middle Aged ; Performance enhancement ; Real-Time Polymerase Chain Reaction ; ROC Curve ; Sensitivity ; Sensitivity and Specificity</subject><ispartof>Clinical cancer research, 2017-04, Vol.23 (8), p.2061-2070</ispartof><rights>2016 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research Inc Apr 15, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-f457871ee07e32553bd37476814371d7146bf6c701073a67408209d76009fbec3</citedby><cites>FETCH-LOGICAL-c535t-f457871ee07e32553bd37476814371d7146bf6c701073a67408209d76009fbec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27697996$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liang, Qiaoyi</creatorcontrib><creatorcontrib>Chiu, Jonathan</creatorcontrib><creatorcontrib>Chen, Yingxuan</creatorcontrib><creatorcontrib>Huang, Yanqin</creatorcontrib><creatorcontrib>Higashimori, Akira</creatorcontrib><creatorcontrib>Fang, Jingyuan</creatorcontrib><creatorcontrib>Brim, Hassan</creatorcontrib><creatorcontrib>Ashktorab, Hassan</creatorcontrib><creatorcontrib>Ng, Siew Chien</creatorcontrib><creatorcontrib>Ng, Simon Siu Man</creatorcontrib><creatorcontrib>Zheng, Shu</creatorcontrib><creatorcontrib>Chan, Francis Ka Leung</creatorcontrib><creatorcontrib>Sung, Joseph Jao Yiu</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><title>Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.
Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.
Candidates identified by metagenome sequencing, including
(
),
(
),
(
),
(
), and one undefined species (labeled as
), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (
= 0.801-0.934, all
< 0.0001).
was significantly more abundant in colorectal cancer than controls (
< 0.0001), with AUROC of 0.868 (
< 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity,
discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (
+
+
-
) showed an improved diagnostic ability compared with
alone (AUROC = 0.886,
< 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of
alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.
Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.
.</description><subject>Adult</subject><subject>Aged</subject><subject>Area Under Curve</subject><subject>Bacteria</subject><subject>Bacteroides</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Cancer</subject><subject>Candidates</subject><subject>Clostridium</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - diagnosis</subject><subject>Colorectal Neoplasms - microbiology</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Experimental design</subject><subject>Feces</subject><subject>Feces - microbiology</subject><subject>Female</subject><subject>Fusobacterium nucleatum</subject><subject>Gastrointestinal Microbiome</subject><subject>Humans</subject><subject>Intestinal microflora</subject><subject>Male</subject><subject>Microbiota</subject><subject>Middle Aged</subject><subject>Performance enhancement</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>ROC Curve</subject><subject>Sensitivity</subject><subject>Sensitivity and Specificity</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqNkU1LxDAQhosofv8EpeDFS9dM833U-gmLgug5pNmpdO02mnQX_Pem7OrBk6cJwzPvZN43y06ATAC4ugAiVUEYLSfOhQJEAVzrrWwfOJcFLQXfTu8fZi87iHFOCDAgbDfbK6XQUmuxn73eorNdfmXdgKG1-aUbchvzR7_C1G39woZ3DDFvfEjNvu1XNrYrzK9b-9b72MbcN3nlOx_QDUmosr3DcJTtNLaLeLyph2nPzUt1X0yf7h6qy2nhOOVD0TAulQREIpGWnNN6RiWTQgGjEmYSmKgb4SRJh1ArJCOqJHomBSG6qdHRw-x8rfsR_OcS42AWbXTYdbZHv4wGlAaV1BT5B0rTnyjRLKFnf9C5X4Y-HWJAK8pAMqoTxdeUCz7GgI35CG2y68sAMWNEZrTfjPabqno2IMwYUZo73agv6wXOfqd-MqHfoHGJmQ</recordid><startdate>20170415</startdate><enddate>20170415</enddate><creator>Liang, Qiaoyi</creator><creator>Chiu, Jonathan</creator><creator>Chen, Yingxuan</creator><creator>Huang, Yanqin</creator><creator>Higashimori, Akira</creator><creator>Fang, Jingyuan</creator><creator>Brim, Hassan</creator><creator>Ashktorab, Hassan</creator><creator>Ng, Siew Chien</creator><creator>Ng, Simon Siu Man</creator><creator>Zheng, Shu</creator><creator>Chan, Francis Ka Leung</creator><creator>Sung, Joseph Jao Yiu</creator><creator>Yu, Jun</creator><general>American Association for Cancer Research Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>7QL</scope><scope>C1K</scope></search><sort><creationdate>20170415</creationdate><title>Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer</title><author>Liang, Qiaoyi ; 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We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.
Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.
Candidates identified by metagenome sequencing, including
(
),
(
),
(
),
(
), and one undefined species (labeled as
), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (
= 0.801-0.934, all
< 0.0001).
was significantly more abundant in colorectal cancer than controls (
< 0.0001), with AUROC of 0.868 (
< 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity,
discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (
+
+
-
) showed an improved diagnostic ability compared with
alone (AUROC = 0.886,
< 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of
alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.
Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research Inc</pub><pmid>27697996</pmid><doi>10.1158/1078-0432.ccr-16-1599</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2017-04, Vol.23 (8), p.2061-2070 |
| issn | 1078-0432 1557-3265 |
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| source | Science Journals (Open access) |
| subjects | Adult Aged Area Under Curve Bacteria Bacteroides Biomarkers Biomarkers, Tumor - analysis Cancer Candidates Clostridium Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - diagnosis Colorectal Neoplasms - microbiology Diagnosis Diagnostic systems Experimental design Feces Feces - microbiology Female Fusobacterium nucleatum Gastrointestinal Microbiome Humans Intestinal microflora Male Microbiota Middle Aged Performance enhancement Real-Time Polymerase Chain Reaction ROC Curve Sensitivity Sensitivity and Specificity |
| title | Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer |
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