GLUT1 and ASCT2 Protein Expression in Papillary Thyroid Carcinoma Patients and Relation to Hepatitis C Virus: A Propensity-Score Matched Analysis

Afaf T Ibrahiem; Manal S Fawzy; Jawaher A Abdulhakim; Eman A Toraih

doi:10.2147/IJGM.S354108

GLUT1 and ASCT2 Protein Expression in Papillary Thyroid Carcinoma Patients and Relation to Hepatitis C Virus: A Propensity-Score Matched Analysis

Int J Gen Med. 2022 Mar 14:15:2929-2944. doi: 10.2147/IJGM.S354108. eCollection 2022.

Authors

Afaf T Ibrahiem^{1

2}, Manal S Fawzy^{3

4}, Jawaher A Abdulhakim⁵, Eman A Toraih^{6

7}

Affiliations

¹ Department of Pathology, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
² Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
³ Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
⁴ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
⁵ Medical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia.
⁶ Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA.
⁷ Genetics Unit, Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Abstract

Purpose: Recently, glucose and amino acid transporters have gradually become a hot topic in thyroid gland biology and cancer research. We aimed to investigate the expressions of glucose transporter 1 (GLUT1) and glutamine transporter 2 (ASCT2) in papillary thyroid carcinoma (PTC) and their clinical significance and relation to HCV-related hepatitis.

Patients and methods: Screening 202 TC tissue samples against the selection criteria using a propensity-score matched analysis to adjust for age, sex, side of tumor, histopathological variants, TNM staging system, and the positivity for HCV yielded 51 matched (17 HCV positive and 34 HCV negative) PTC samples. The expressions of GLUT1 and ASCT2 expressions were detected by immunohistochemical staining. Kaplan-Meier survival curves were generated for disease-free and overall survival, and multivariate Cox regression analysis was applied to identify predictors for mortality.

Results: Of 51 thyroid cancer tissues, 85% showed positive GLUT1 cytoplasmic staining, and 26% had a high expression score. All thyroid cancer specimens demonstrated ASCT2 cytoplasmic staining with membranous accentuation. Of these, 78% showed a high expression score, and 22% showed weak staining. On stratifying the study cohort based on the HCV status, HCV negative cohort showed a significantly higher immunoreactivity score for GLUT1 (p = 0.004) but not ASCT2 (p = 0.94) than HCV positive group. The expressions of the studied transporters showed no significant associations with the prognostic features of PTC nor the disease-free/overall survival.

Conclusion: GLUT1 and ASCT2 immunohistochemical staining showed positive expression with variable intensity in nearly 85% and 100% of PTC tissue samples compared to normal ones, respectively. Furthermore, GLUT1 protein expression, not ASCT2, showed a higher immunoreactivity score in PTC patients who are negative for HCV than cancer patients with positive HCV. Meanwhile, the expression of both protein markers was not associated with the clinicopathological characteristics of the studied PTC patients. Further large-scale multicenter studies are recommended to validate the present findings.

Keywords: HCV; glucose transporter 1; glutamine transporter 2; immunohistochemistry; papillary thyroid cancer.

Grants and funding

The authors would like to acknowledge the approval and the support of this research study by grant No. (F-7954-MED-2018-3-9) from the Deanship of Scientific Research, Northern Border University, Arar, Saudi Arabia.