Use of AKR1C1 and TKTL1 in the Diagnosis of Low-grade Squamous Intraepithelial Lesions from Mexican Women

Abstract

Background/Aim: To determine the differential protein profiles of cervical cancer cell lines in order to find potential targets that can be used as biomarkers in low-grade squamous intraepithelial lesions (LSIL) diagnosis. Materials and Methods: Proteomic analysis was performed on cervical cancer cell lines by 2D electrophoresis and liquid chromatography-mass spectrometry. Biomarker validation was performed in histological samples by immunofluorescence. Results: Aldo-keto reductase C1 (AKR1C1) and transketolaselike 1 (TKTL1) proteins were selected as biomarkers and their expression was increased in samples with LSIL diagnosis. TKTL1 in combination with AKR1C1 increased sensitivity and specificity to 75% and 66%, respectively, with an area under curve of 0.76 in receiver operating characteristics curve analysis. Conclusion: AKR1C1 and TKTL1 showed potential as biomarkers for diagnosis of LSIL in Mexican women, with similar sensitivity and specificity to the biomarkers used in clinical trials for diagnosis of LSIL.Cervical cancer (CC) takes second place in incidence and mortality by cancer in women between 15 and 60 years old (1). CC has a high impact in developing countries; in Africa and Central America it is the leading cause of cancer-related death among women with 85% of cases (2), and takes second place for women in Mexico (3). For all CC stages, the 3-to 5-year survival rate in undeveloped countries is less than 50%, with best results being obtained with radical hysterectomy (4). Screening methods for CC and squamous intraepithelial lesions or cervical intraepithelial neoplasia (CIN) include cytology (conventional and liquid-based) and human papillomavirus (HPV) test, alone or in combination. It is common that colposcopy and histopathology accompany these methods according to a woman's age, screening history, risk factors, and the choice of screening test available (5).Low-grade squamous intraepithelial lesion (LSIL) has been defined as a cytological diagnosis for patients with smears showing cytological criteria of permissive HPV infection. In histopathological diagnosis LSIL and CIN1 are used synonymously, and the gold standard for the definition of uterine cervical disease is histopathological evaluation (6). However, there is a discrepancy among pathologists about LSIL management due to variable progression: In 70% of cases, lesion regression occurs and only 10% progress to a high-grade squamous intraepithelial lesion (HSIL) (7). The use of cancer-specific biomarkers has been evaluated for diagnosis and treatment with a minimally invasive effect and the potential to lower the cost of diagnosis (8). Ki-67 and p16 INK4A are biomarkers proteins that play an important role in clinical diagnosis and differential diagnosis between dysplastic and non-dysplastic lesions (9). The grade of dysplasia is correlated with Ki-67 expression in the progression of LSIL, however, Ki-67 staining cannot distinguish between dysplasia and immature squamous metaplasia. p16 INK4A is a useful diagnostic adjunct for SIL, also disc...

TKTL1 participated in malignant progression of cervical cancer cells via regulating AKT signal mediated PFKFB3 and thus regulating glycolysis

“…Current study has shown that TKTL1 expression, which is increased in human endometrial cancer, is related to AKT phosphorylation level and GLUT1 [ 14 ]. In addition, the increased expression of TKTL1 has been proved to be a diagnostic marker in low-grade CC [ 15 ]. At the same time, study has confirmed that TKTL1 expression is increased in CC and can be used as a diagnostic marker for CC [ 16 ].…”