{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:31:25Z","timestamp":1790573485547,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Histopathological examination is the gold standard for detection of gallstone (GS) or gallbladder carcinoma (CAGB). Bile concentrated in the gallbladder (GB) is expected to recapitulate metagenomics and molecular changes associated with development of CAGB.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Bile samples were screened for lipidomics and metaproteome (metagenomics) signatures capable of early detection of cancer in GB anomalies. Analysis of the training cohort (<jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a087) showed that metastability of bile was reduced in CAGB (<jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u00a00.05). CAGB bile showed significant alteration of lipidome and microbiome as indicated by multivariate partial least squares regression analysis and alpha\u2010diversity and beta\u2010diversity indexes (<jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u00a00.05). Significant reduction of lipid species and increase in bacterial taxa were found to be associated with patients with CAGB, CAGB with GS, and GS (<jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u00a00.05, log fold change &gt;1.5). A multimodular correlation network created using weighted lipid\/metaproteomic correlation network analysis showed striking associations between lipid and metaproteomic modules and functionality. CAGB\u2010linked metaproteomic modules\/functionality directly correlated with lipid modules, species, clinical parameters, and bile acid profile (<jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u00a00.05). Increased bacterial taxa (<jats:italic toggle=\"yes\">Leptospira<\/jats:italic>, <jats:italic toggle=\"yes\">Salmonella enterica<\/jats:italic>, <jats:italic toggle=\"yes\">Mycoplasma gallisepticum<\/jats:italic>) and their functionality showed a direct correlation with lipid classes such as lysophosphatidylinositol, ceramide 1\u2010phosphate, and lysophosphatidylethanolamine and development of CAGB (<jats:italic toggle=\"yes\">r<\/jats:italic>\n                                 <jats:sup>2<\/jats:sup>\u00a0&gt;\u00a00.85). Lipid\/metaproteomic signature\u2013based probability of detection for CAGB was\u00a0&gt;\u00a090%, whereas that for GS was\u00a0&gt;\u00a080% (<jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u00a00.05). Validation of eight lipid species using four machine learning algorithms in two separate cohorts (<jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a038; bile [test cohort 1] and paired plasma [test cohort 2]) showed accuracy (99%) and sensitivity\/specificity (&gt;98%) for CAGB detection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Bile samples of patients with CAGB showed significant reduction in lipid species and increase in bacterial taxa. Our study identifies a core set of bile lipidome and metaproteome signatures which may offer universal utility for early diagnosis of CAGB.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32496","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T11:33:09Z","timestamp":1648726389000},"page":"920-935","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":35,"title":["Bile multi\u2010omics analysis classifies lipid species and microbial peptides predictive of carcinoma of gallbladder"],"prefix":"10.1097","volume":"76","author":[{"given":"Nupur","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babu","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasundhra","family":"Bindal","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6727-9120","authenticated-orcid":false,"given":"Sanyam","family":"Falari","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viniyendra","family":"Pamecha","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-362X","authenticated-orcid":false,"given":"Jaswinder Singh","family":"Maras","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"hep32496-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.suc.2018.12.008","article-title":"Gallbladder cancer: diagnosis, surgical management, and adjuvant therapies","volume":"99","year":"2019","journal-title":"Surg Clin North Am"},{"key":"hep32496-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1186\/s12885-018-4575-3","article-title":"Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico","volume":"18","year":"2018","journal-title":"BMC Cancer"},{"key":"hep32496-bib-0003-20250824","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/1097-0142(19800301)45:5<919::AID-CNCR2820450514>3.0.CO;2-4","article-title":"The precursor lesions of invasive gallbladder carcinoma. 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