Title Uloga GLUT1 i HIF-1α u metabolizmu karcinoma pluća Title (english) Role of GLUT1 and HIF-1α in lung cancer metabolism Author Josipa Kokeza Mentor Sandra Zekić Tomaš (mentor)Committee member Merica Glavina Durdov (predsjednik povjerenstva)Committee member Snježana Tomić (član povjerenstva)Committee member Ana Marušić (član povjerenstva)Granter University of Split Defense date and country 2024-10-16, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Cilj istraživanja: U karcinomu pluća nemalih stanica (NSCLC) odrediti izražaj GLUT1 u primarnom tumoru i metastatskom limfnom čvoru, izražaj HIF-1α i HIF1A mRNA u primarnom tumoru i usporediti ih s preoperativnom SUVmax vrijednošću u PET/CT s uporabom FDA, histološkim tipom i drugim kliničkim i patološkim parametrima. Materijal i metode: U uzorku je 48 ispitanika s NSCLC-om koji su podvrgnuti lobektomiji/pulmektomiji s medijastinalnom limfadenektomijom u KBC-u Split od 2013. do 2018. Podaci o nakupljanju FDG i kliničko-patološkim parametrima prikupljeni su iz medicinske dokumentacije. Preparati su izrezani iz parafinskih blokova tumorskog tkiva i metastatskog limfnog čvora. Imunohistokemijski su strojno obojeni na GLUT1 i mikroskopski analizirani metodom HSCORE. Ručno su obojeni na HIF-1α metodom imunofluorescencije te je određen postotak tumorskih stanica koje su pokazale nuklearno odnosno nuklearno/citoplazmatsko bojenje na HIF-1α. Metodom qPCR analizirana je razlika u HIF-1A mRNA adenokarcinoma i karcinoma pločastih stanica. Rezultati su statistički analizirani i značajnom je određena razlika na razini p = 0.05. Rezultati: 32 ispitanika su bili muškarci i 16 žene, 34 (70.83%) s adenokarcinomom i 14 (29.16%) s karcinomom pločastih stanica. U karcinomu pločastih stanica je izražaj GLUT1 u primarnom tumoru i metastatskom limfnom čvoru bio veći nego u adenokarcinomu (p<0.0001 odnosno p<0.0196). U karcinomu pločastih stanica bio je veći postotak stanica s nuklearnim i nuklearno/citoplazmatskim izražajem HIF-1α nego u adenokarcinomu (p = 0.0025 odnosno p = 0.0038). U karcinomu pločastih stanica utvrđena je povezanost između nuklearnog i nuklearno/citoplazmatskog izražaja HIF-1α (p = 0.0004). Nije pronađena statistički značajna razlika u izražaju HIF-1α ovisno o stadiju bolesti. Nuklearni/citoplazmatski izražaj HIF-1α veći je u muškaraca nego u žena (p=0.0089). Izražaj GLUT1 je povezan s nuklearnim i nuklearnim/citoplazmatskim izražajem HIF-1α (p=0.0392 odnosno p=0.0498). Nije utvrđena značajna razlika HIF-1A mRNA u odnosu na histološki tip ili SUVmax primarnog tumora. Zaključak: Dokazane razlike u izražaju GLUT1, HIF-1α i SUVmax u odnosu na tip NSCLC a potvrđuju metaboličku heterogenost između adenokarcinoma i karcinoma pluća pločastih stanica.
Abstract (english) Aim of the study: In non-small cell lung cancer (NSCLC) to determine the expression of GLUT1 in the primary tumor and metastatic lymph node, the expression of HIF-1α and HIF1A mRNA in the primary tumor and compare them with the preoperative SUVmax value in PET/CT using FDA, histological type and other clinical and pathological parameters. Material and methods: The sample includes 48 patients with NSCLC who underwent lobectomy/pulmectomy with mediastinal lymphadenectomy at University Hospital Split from 2013 to 2018. Data on FDG accumulation and clinicopathological parameters were collected from medical records. The histologic slides were cut from paraffin blocks of tumor tissue and metastatic lymph node. They were stained immunohistochemically for GLUT1 and microscopically analyzed using the HSCORE method. They were manually stained for HIF-1α using the immunofluorescence method, and the percentage of tumor cells that showed nuclear or nuclear/cytoplasmic staining for HIF-1α was determined. The difference in HIF-1A mRNA of adenocarcinoma and squamous cell carcinoma was analyzed using the qPCR method. The results were statistically analyzed and a significant difference was determined at the p = 0.05. Results: 32 patients were men and 16 women, 34 (70.83%) with adenocarcinoma and 14 (29.16%) with squamous cell carcinoma. In squamous cell carcinoma, GLUT1 expression in the primary tumor and metastatic lymph node was higher than in adenocarcinoma (p<0.0001 and p<0.0196, respectively). In squamous cell carcinoma, there was a higher percentage of cells with nuclear and nuclear/cytoplasmic expression of HIF-1α than in adenocarcinoma (p = 0.0025 and p = 0.0038, respectively). In squamous cell carcinoma, an association between nuclear and nuclear/cytoplasmic expression of HIF-1α was established (p=0.0004). No statistically significant difference was found in the expression of HIF-1α depending on the stage of the disease. The nuclear/cytoplasmic expression of HIF-1α was higher in men than in women (p=0.0089). GLUT1 expression was associated with nuclear and nuclear/cytoplasmic expression of HIF-1α (p=0.0392 and p=0.0498, respectively). No significant difference was found in HIF-1A mRNA in relation to the histological type or SUVmax of the primary tumor. Conclusion: Proven differences in the expression of GLUT1, HIF-1α and SUVmax in relation to the type of NSCLC confirm the metabolic heterogeneity between adenocarcinoma and squamous cell lung cancer.
Keywords
Karcinom pluća nemalih stanica
transporter glukoze tipa 1 (GLUT1)
faktor 1 inducibilan hipoksijom alfa podjedinice (HIF-1α)
Keywords (english)
Non-Small-Cell Lung Carcinoma
Glucose Transporter Type 1 (GLUT1)
alpha Subunit Hypoxia-Inducible Factor 1 (HIF-1α)
Language croatian URN:NBN urn:nbn:hr:171:942949 Study programme Title: Biology of Neoplasms Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2024-10-07 07:33:45
