Prognostic Significance of mTOR Expression in Recurrence Following Hepatic Metastasectomy in Colorectal Cancer

MakaleAçık ErişimScopus SJRQ1

Özet

Surgery is one of the most effective treatment methods for liver metastases developing from primary colorectal cancer (CRC). Despite the widespread application of surgical approaches, recurrence rates remain substantial. Although chemotherapy is frequently employed, the supporting evidence for its efficacy in this context remains inconclusive. In the present study, we aimed to identify potential predictors of post-metastasectomy recurrence by analyzing clinical, pathological, and molecular features of both primary colorectal tumors and their corresponding hepatic metastases. Specifically, we evaluated the expression of epithelial–mesenchymal transition (EMT) markers, cancer stem cell (CSC) markers, and selected oncogenic mRNAs (RAS, mTOR, and CMYC) in tissue samples from 84 patients. RAS and CMYC are well-known proto-oncogenes involved in cell proliferation and survival, while mTOR functions as a central regulator of cell growth and metabolism. Following liver metastasectomy, intra-hepatic recurrence was observed in 40.5% of the cases. Among the molecular markers analyzed, the EMT transcription factor SNAIL—which plays a critical role in cancer cell invasion and metastasis—and mTOR exhibited significantly elevated expression in metastatic lesions from patients who experienced recurrence. While SNAIL expression did not show a clear association with the time to recurrence, increased mTOR expression in metastatic liver tissue was significantly associated with both shorter recurrence-free survival and diminished overall survival (p < 0.001). Results showed that mTOR expression levels could be a clinically relevant predictive indicator of remnant liver recurrence. In patients with liver metastases, the use of mTOR inhibitors may be considered after hepatic metastasectomy.

Anahtar Kelimeler

RDL Kalıcı Bağlantı (PID)
https://rdlopen.rawdatalibrary.net/r/kostu/10661Resmi atıflarda kullanılan kalıcı adres
DOI
https://doi.org/10.3390/life15060877Yayıncı resmi DOI adresi
İndeks kayıtları
Kaydın indeks veri tabanlarındaki sayfası (aktarımda alınan kayıt numarasıyla). Erişim, indeksin kendi koşullarına bağlıdır.
Atıflar
Scopus
0
WoS
0
Her kaynağın kendi saydığı toplam atıf; aktarım ve zenginleştirme sırasında alındı.
Tam Kayıt
AlanDeğerDil
dc.contributor.authorAksoy, Fuat
dc.contributor.authorAk-Aksoy, Secil
dc.contributor.authorKaramustafaoglu, Ahmet
dc.contributor.authorTekin, Cagla
dc.contributor.authorErcelik, Melis
dc.contributor.authorTunca, Berrin
dc.contributor.authorDuman, Busra Oncel
dc.contributor.authorIsik, Ozgen
dc.contributor.authorUgras, Nesrin
dc.contributor.authorKaya, Ekrem
dc.date.accessioned2026-10-27T23:47:43.154592424Z
dc.date.available2026-10-27T23:47:43.154592424Z
dc.date.issued2025
dc.description.abstractSurgery is one of the most effective treatment methods for liver metastases developing from primary colorectal cancer (CRC). Despite the widespread application of surgical approaches, recurrence rates remain substantial. Although chemotherapy is frequently employed, the supporting evidence for its efficacy in this context remains inconclusive. In the present study, we aimed to identify potential predictors of post-metastasectomy recurrence by analyzing clinical, pathological, and molecular features of both primary colorectal tumors and their corresponding hepatic metastases. Specifically, we evaluated the expression of epithelial–mesenchymal transition (EMT) markers, cancer stem cell (CSC) markers, and selected oncogenic mRNAs (RAS, mTOR, and CMYC) in tissue samples from 84 patients. RAS and CMYC are well-known proto-oncogenes involved in cell proliferation and survival, while mTOR functions as a central regulator of cell growth and metabolism. Following liver metastasectomy, intra-hepatic recurrence was observed in 40.5% of the cases. Among the molecular markers analyzed, the EMT transcription factor SNAIL—which plays a critical role in cancer cell invasion and metastasis—and mTOR exhibited significantly elevated expression in metastatic lesions from patients who experienced recurrence. While SNAIL expression did not show a clear association with the time to recurrence, increased mTOR expression in metastatic liver tissue was significantly associated with both shorter recurrence-free survival and diminished overall survival (p < 0.001). Results showed that mTOR expression levels could be a clinically relevant predictive indicator of remnant liver recurrence. In patients with liver metastases, the use of mTOR inhibitors may be considered after hepatic metastasectomy.
dc.description.sponsorshipBursa Uludağ Üniversitesi, BUU, (THIZ-2024-1810)
dc.description.sponsorshipBursa Uludağ Üniversitesi, BUU
dc.identifier.articlenumber877
dc.identifier.doi10.3390/life15060877
dc.identifier.eissn2075-1729
dc.identifier.issn2075-1729
dc.identifier.issue6
dc.identifier.pmcidPMC12194524
dc.identifier.pmid40566531
dc.identifier.scopus2-s2.0-105009115043
dc.identifier.urihttps://rdlopen.rawdatalibrary.net/r/kostu/10661
dc.identifier.volume15
dc.identifier.wosWOS:001517072500001
dc.language.isoen
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.relation.ispartofLife
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectcolorectal cancer
dc.subjectliver metastasis
dc.subjectmetastasectomy
dc.subjectmTOR
dc.subjectrecurrence
dc.subject.classificationBiology
dc.subject.classificationMicrobiology
dc.subject.classificationLife Sciences & Biomedicine - Other Topics
dc.titlePrognostic Significance of mTOR Expression in Recurrence Following Hepatic Metastasectomy in Colorectal Cancer
dc.typeArticle
rdl.citation.scopus0
rdl.citation.wos0
rdl.departmentDepartment of General Surgery, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey
rdl.departmentDepartment of Medical Microbiology, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey
rdl.departmentDepartment of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey
rdl.departmentEuropean Vocational School, Medical Laboratory Techniques Program, Kocaeli Health and Technology University, Kocaeli 41275, Turkey
rdl.departmentDepartment of General Surgery, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
rdl.departmentDepartment of Pathology, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey
rdl.oa.statusgold
rdl.oa.statusgreen
rdl.oa.urlhttps://www.mdpi.com/2075-1729/15/6/877/pdf?version=1748513591
rdl.scopus.quartileQ1
rdl.source.indexSCOPUS
rdl.source.indexWOS
rdl.source.indexPUBMED
rdl.wos.indexScience Citation Index Expanded (SCI-EXPANDED)