# Expression of Hexokinase-2 (HK2), Glutaminase-1 (GLS1) and Fatty Acid Synthase (FASN) in Gastric Cancer and Their Prognostic Significance **Authors:** Elisa García-Martínez, Leonardo S. Lino-Silva, Adriana Romo-Pérez, Leticia Bornstein-Quevedo, Alma Chavez-Blanco, Guadalupe Dominguez-Gomez, Horacio N. Lopez-Basave, Alejandro Padilla-Rosciano, Consuelo Diaz-Romero, Aurora Gonzalez-Fierro, Alfonso Duenas-Gonzalez PMC · DOI: 10.3390/medsci14010148 · 2026-03-19 ## TL;DR This study examines the expression of three metabolic enzymes in gastric cancer and their potential as prognostic markers and therapeutic targets. ## Contribution The study identifies co-expression of HK2, GLS1, and FASN as a potential prognostic marker and therapeutic target in advanced gastric cancer. ## Key findings - HK2 and FASN overexpression correlates with advanced tumor stage in gastric cancer. - Co-expression of HK2/FASN and HK2/GLS1/FASN is associated with disease progression. - Only tumor stage remains a significant prognostic factor in multivariate analysis. ## Abstract Background/Objectives: To evaluate the immunohistochemical expression of hexokinase-2 (HK2), glutaminase-1 (GLS1), and fatty acid synthase (FASN) and its prognostic significance in diffuse gastric adenocarcinoma. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples from 92 patients with diffuse gastric adenocarcinoma were analyzed. Immunohistochemistry (IHC) was performed to assess the expression of HK2, GLS1 and FASN. Expression levels were evaluated semi-quantitatively based on staining intensity and the percentage of positive cells. Associations between enzyme expression and clinicopathological features were assessed using the Chi-square test. Kaplan–Meier survival analysis was employed to evaluate progression-free survival (PFS) and overall survival (OS) and the log-rank test and Cox proportional hazards models were used for statistical analysis. Results: HK2 and FASN were overexpressed in 20.7% and 22.8% of patients, respectively, and were significantly associated with advanced tumor stage. In contrast, GLS1 expression, found in 30.4% of patients, did not independently correlate with clinicopathological characteristics. Furthermore, HK2 expression and co-expression of HK2/FASN (10.9%) and HK2/GLS1/FASN (8.7%) were associated with progressive disease. In the univariate analysis, stage, HK2 overexpression, and co-expression of HK2/FASN and HK2/GLS1/FASN were associated with shorter survival. However, only stage retained prognostic value in the multivariate analysis. Conclusions: Co-expression of these key metabolic enzymes remains a promising candidate as prognostic markers and therapeutic targets. Concurrent targeting of these metabolic pathways may offer novel therapeutic opportunities for patients with advanced-stage gastric cancer. ## Linked entities - **Genes:** HK2 (hexokinase 2) [NCBI Gene 3099], GLS (glutaminase) [NCBI Gene 2744], FASN (fatty acid synthase) [NCBI Gene 2194] - **Diseases:** gastric cancer (MONDO:0001056), diffuse gastric adenocarcinoma (MONDO:0005017) ## Full-text entities - **Genes:** HK2 (hexokinase 2) [NCBI Gene 3099] {aka HKII, HXK2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, GLS (glutaminase) [NCBI Gene 2744] {aka AAD20, CASGID, DEE71, EIEE71, GAC, GAM}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, HK1 (hexokinase 1) [NCBI Gene 3098] {aka CNSHA5, HK, HK1-ta, HK1-tb, HK1-tc, HKD}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1} - **Diseases:** overweight (MESH:D050177), Cancer (MESH:D009369), lymph node metastasis (MESH:D008207), diffuse (MESH:D008228), necrosis (MESH:D009336), tumorigenesis (MESH:D063646), deaths (MESH:D003643), injury to (MESH:D014947), H&E (MESH:D016751), PD (MESH:D010300), DGC (MESH:D013274) - **Chemicals:** H&E (MESH:D006371), glutamate (MESH:D018698), DON (MESH:C005914), lonidamine (MESH:C016371), alpha-KG (MESH:D007656), Formalin (MESH:D005557), orlistat (MESH:D000077403), paraffin (MESH:D010232), glucose (MESH:D005947), acetyl-CoA (MESH:D000105), glucose-6-phosphate (MESH:D019298), pyruvate (MESH:D019289), palmitate (MESH:D010168), trastuzumab (MESH:D000068878), FA (MESH:D005227), glutamine (MESH:D005973), 2-deoxy-d-glucose (MESH:D003847), citrate (MESH:D019343), 5-Fluouracil (-), oleanolic acid (MESH:D009828), TCA (MESH:D014238), Licochalcone A (MESH:C070840), 5-Fluorouracil (MESH:D005472), Cisplatin (MESH:D002945), lipid (MESH:D008055), NADPH (MESH:D009249), malonyl-CoA (MESH:D008316), Epirubicin (MESH:D015251) - **Species:** Homo sapiens (human, species) [taxon 9606] - **Cell lines:** NCI-N87 — Homo sapiens (Human), Gastric tubular adenocarcinoma, Cancer cell line (CVCL_1603), MGC80-3 — Homo sapiens (Human), Hybrid cell line (CVCL_5334), AGS — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0139), SGC-7901 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0520), MKN-45 — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0434) ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13027862/full.md --- Source: https://tomesphere.com/paper/PMC13027862