Abstract
Glucose transporter-1 (GLUT1) has been proposed as a prognosticator in various cancers associated with therapeutic resistance and immune evasion; however little data is available on the role of GLUT1 in cervical cancer. Most cervical cancers are caused by human papilloma virus (HPV), but studies on the treatment response and prognosis depending on the HPV subtype, are conflicting. This hypothesis-generating study aims to investigate the prognostic impact of GLUT1 in cervical cancer, in conjunction with HPV subtype. Clinicopathologic factors, along with mRNA expression data were obtained using The Cancer Genome Atlas database. Tumor HPV status and immune cell scores were extracted from previous publications. In total, 298 patients were analyzed. High GLUT1 expression was associated with old age, squamous cell carcinoma, high tumor stage, pelvic lymph node metastases, and low hysterectomy rate. Multivariate survival analysis revealed that high GLUT1 expression (Hazard ratio (HR) 2.57, p = 0.002) and HPV16 subtype (HR 0.56, p = 0.033) were independent prognostic factors for overall survival. In the subgroup analysis, poor prognostic impact of high GLUT1 expression was maintained in HPV16-positive group (p < 0.001), but not in HPV16-negative group (p = 0.495). Decreased immune cell scores of CD8+ T cells, B cells, and Th1 cells by high GLUT1 expression were observed only in HPV16-positive group. In conclusion, these results suggested that GLUT1 expression and HPV16 subtype might have an independent prognostic value in cervical cancer. GLUT1-mediated immunomodulation might be an important cause of treatment failure, especially in HPV16-positive group.
Highlights
Cervical cancer is still occurring worldwide at a considerable frequency despite significant advances in the screening of pre-invasive lesion, as well as modern prevention strategies with the high-risk human papilloma virus (HPV) vaccination[1]
18 patients were negative for all types of HPV (6.0%)
We demonstrated that high glucose transporter-1 (GLUT1) expression and HPV16 subtype are independent prognostic factors in cervical cancer
Summary
Cervical cancer is still occurring worldwide at a considerable frequency despite significant advances in the screening of pre-invasive lesion, as well as modern prevention strategies with the high-risk human papilloma virus (HPV) vaccination[1]. HPV infection has been considered as an important cause of cervical cancer, studies on the treatment response and prognosis according to the different HPV subtypes are conflicting[2,3,4]. Several studies suggested that HPV genotypes might be associated with the prognosis of cervical cancer patients treated with radiotherapy[5,6]. Lymph node metastasis, lymphovascular invasion, and tumor size are commonly used to predict the prognosis, patients with similar prognostic factors often experience very different therapeutic responses in actual clinics. To elucidate the effect of the combination of HPV genotypes and tumor metabolism, mediated by GLUT1, on the treatment outcomes and tumor microenvironment in cervical cancer, we analyzed these biomarkers in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), using The Cancer Genome Atlas (TCGA) database
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