{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T22:55:43Z","timestamp":1770159343401,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research (ICMR), Govt. of India","doi-asserted-by":"publisher","award":["2020-0109"],"award-info":[{"award-number":["2020-0109"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Gallbladder cancer (GBC) is a highly aggressive malignancy characterized by a poor prognosis, particularly in its advanced stages. While microRNAs (miRNAs) regulate cancer progression, their specific role in the transition from early to advanced GBC is poorly understood. Methods: We performed miRNA expression profiling on 41 formalin-fixed paraffin-embedded (FFPE) tissues, including 10 gallstone disease (GSD) controls, 14 early-stage GBC (stage I and II), and 17 advanced-stage GBC cases (stage III and IV), using the NanoString nCounter platform. Differentially expressed miRNAs (DEMs) were identified followed by miRNA target identification using miRTarBase. Results: We identified 43 significantly dysregulated miRNAs in early-stage and 46 in advanced-stage GBC compared to controls. Based on the literature search, we found EMT-inhibiting miRNAs (miR-200 family) to be overexpressed in early stage and downregulated in advanced stages (miR-574-3p, miR-195-5p) in our study. Pathway analysis revealed significant enrichment of the \u2018EGFR tyrosine kinase inhibitor resistance\u2019 pathway in both the stages. The correlation of DEMs with clinicopathological features revealed that the expression of miR-361-3p and miR-423-5p was significantly associated with tumor grade (r = \u22120.605, p = 0.0003) and lymph node status (r = \u22120.621, p = 0.0001), respectively. Conclusions: This study identifies distinct miRNA signatures associated with GBC initiation and progression, offering insights into the molecular pathogenesis of the disease. Furthermore, functional studies of the miRNAs implicated in EMT and EGFR-TKI resistance may be conducted using GBC cell lines to dissect the precise roles of key miRNAs and explore their potential as novel therapeutic targets in GBC.<\/jats:p>","DOI":"10.3390\/cancers18030502","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:48:01Z","timestamp":1770115681000},"page":"502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stage-Specific miRNA Profiling Reveals Key Regulators of EMT and EGFR-TKI Resistance in Gallbladder Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Neeraj","family":"Saklani","sequence":"first","affiliation":[{"name":"ICMR-Centre for Cancer Pathology (Formerly a Part of ICMR-National Institute of Pathology), Safdarjung Hospital Campus, New Delhi 110029, India"},{"name":"Faculty of Health Sciences, Manipal Academy of Higher Education (MAHE), Manipal 576104, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puja","family":"Sakhuja","sequence":"additional","affiliation":[{"name":"Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi 110002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surbhi","family":"Goyal","sequence":"additional","affiliation":[{"name":"Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi 110002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil Kumar","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi 110002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4691-433X","authenticated-orcid":false,"given":"Sarangadhara Appala Raju","family":"Bagadi","sequence":"additional","affiliation":[{"name":"ICMR-Centre for Cancer Pathology (Formerly a Part of ICMR-National Institute of Pathology), Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3804-6157","authenticated-orcid":false,"given":"Poonam","family":"Gautam","sequence":"additional","affiliation":[{"name":"ICMR-Centre for Cancer Pathology (Formerly a Part of ICMR-National Institute of Pathology), Safdarjung Hospital Campus, New Delhi 110029, India"},{"name":"Faculty of Health Sciences, Manipal Academy of Higher Education (MAHE), Manipal 576104, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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