Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Chatzidakis Ioannis
Dissertation committee:
Οικονομόπουλος Θεοφάνης, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πεκτασίδης Δημήτριος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παπαδημητρίου Χρίστος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ράπτης Αθανάσιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τριανταφύλλου Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τσιριγώτης Παναγιώτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ψυρρή Αμάντα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μοριακοί δείκτες (Προβλεπτικοί, Προγνωστικοί παράγοντες) καρκίνου του στομάχου
Translated title:
Molecular markers (predictive, prognostic) of gastric cancer
Summary:
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. Complete surgical resection is required to cure gastric cancer. However, given the high recurrence rate after surgery, additional therapeutic approaches have been explored. These therapeutic strategies include adjuvant concurrent chemotherapy and radiation, perioperative chemotherapy and adjuvant chemotherapy. Several clinical trials have clearly demonstrated the benefit of these adjunctive approaches compared to surgery alone. Especially in early-stage gastric, we evaluated the prognostic significance of immunohistochemical and genetic biomarkers in patients with resected gastric adenocarcinoma cancer to improve patient selection for adjuvant chemoradiotherapy. Tumors from 119 patients were subjected to immunohistochemistry for 12 protein biomarkers, as well as next-generation sequencing. Clinical and biomarker data were available for 91 patients. EBV-positive tumors and tumors with mutations had higher intratumoral CD8 tumor-infiltrating lymphocyte density (p=0.009 and p=0.017, respectively). PIK3CA mutations were correlated with VEGFA overexpression (p=0.042), while KRAS mutations and HER2 expression were mutually exclusive (p=0.036). PTEN expression univariately confirmed longer overall survival (HR=0.27; p=0.046), while there was a trend between the presence of KRAS mutations and inferior disease-free and overall survival. PTEN protein expression and KRAS mutations may predict disease outcome in early-stage gastric cancer. Our study has certain limitations. A major limitation is its small sample size, which may have obscured the prognostic significance of certain genetic or protein biomarkers. These results need to be further validated in larger cohorts.
In summary, we evaluated a large panel of genetic and protein biomarkers in a cohort of patients with gastric cancer who underwent surgery and adjuvant chemoradiotherapy. The validation of these findings, may have significant implications for the prognostic classification of operable gastric cancer and could identify patients who would benefit from intensification of adjuvant therapy or novel treatment strategies to prevent recurrence.
Main subject category:
Health Sciences
Keywords:
Gastric cancer, Molecular markers, Predictive markers, Prognostic markers
Number of references:
205
