PMID- 31465717 OWN - NLM STAT- MEDLINE DCOM- 20201218 LR - 20230710 IS - 1840-4812 (Electronic) IS - 1512-8601 (Print) IS - 1512-8601 (Linking) VI - 20 IP - 1 DP - 2020 Feb 5 TI - Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection. PG - 78-87 LID - 10.17305/bjbms.2019.4359 [doi] AB - Aberrant metabolic regulation has been observed in human cancers, but the corresponding regulation in human papillomavirus (HPV) infection-associated cervical cancer is not well understood. Here, we explored potential biomarkers for the early prediction of cervical carcinoma based on the metabolic profile of uterine cervical tissue specimens that were positive for HPV16 infection. Fifty-two fresh cervical tissues were collected from women confirmed to have cervical squamous cell carcinoma (SCC; n = 21) or cervical intraepithelial neoplasia (CIN) stages II-III (n = 20). Eleven healthy women constituted the controls (negative controls [NCs]). Real-time polymerase chain reaction (PCR) was performed to detect HPV infection in the tissues. High-resolution magic angle spinning nuclear magnetic resonance was utilized for the analysis of the metabolic profile in the tissues. The expression of rate-limiting enzymes involved in key metabolic pathways was detected by reverse-transcription quantitative PCR. An independent immunohistochemical analysis was performed using 123 cases of paraffin-embedded cervical specimens. A profile of 17 small molecular metabolites that showed differential expression in HPV16-positive cervical SCC or CIN II-III compared with HPV-negative NC group was identified. According to the profile, the levels of alpha- and beta-glucose decreased, those of lactate and low-density lipoproteins increased, and the expression of multiple amino acids was altered. Significantly increased transcript and protein levels of glycogen synthase kinase 3 beta (GSK3beta) and glutamate decarboxylase 1 (GAD1) and decreased transcript and protein levels of pyruvate kinase muscle isozyme 2 (PKM2) and carnitine palmitoyltransferase 1A (CPT1A) were observed in the patient group (p < 0.05). HPV infection and cervical carcinogenesis drive metabolic modifications that might be associated with the aberrant regulation of enzymes related to metabolic pathways. FAU - Abudula, Abulizi AU - Abudula A AD - Department of Labour and Environmental Hygienics, School of Public Health, Xinjiang Medical University, Urumqi, China. aabulizi@163.com. FAU - Rouzi, Nuermanguli AU - Rouzi N AD - Department of Labour and Environmental Hygienics, School of Public Health, Xinjiang Medical University, Urumqi, China. rnurimangul@163.com. FAU - Xu, Lixiu AU - Xu L AD - Department of Pathology, School of Basic Medicine, Xinjiang Medical University, Urumqi, China. 15299128270@163.com. FAU - Yang, Yun AU - Yang Y AD - Department of Pathology, School of Basic Medicine, Xinjiang Medical University, Urumqi, China. yangyun1991kyzy@163.com. FAU - Hasimu, Axiangu AU - Hasimu A AD - Department of Pathology, School of Basic Medicine, Xinjiang Medical University, Urumqi, China. hasimu19@163.com. LA - eng PT - Journal Article DEP - 20200205 PL - Bosnia and Herzegovina TA - Bosn J Basic Med Sci JT - Bosnian journal of basic medical sciences JID - 101200947 RN - 0 (Biomarkers) SB - IM MH - Adult MH - Aged MH - Biomarkers/metabolism MH - Carcinoma, Squamous Cell/diagnosis/*metabolism/virology MH - Case-Control Studies MH - Female MH - Humans MH - Metabolomics MH - Middle Aged MH - Papillomavirus Infections/*complications/diagnosis/*metabolism MH - Predictive Value of Tests MH - Uterine Cervical Neoplasms/diagnosis/*metabolism/*virology MH - Uterine Cervical Dysplasia/diagnosis/*metabolism/virology PMC - PMC7029203 COIS- Conflict of interest statement: The authors declare no conflict of interests EDAT- 2019/08/30 06:00 MHDA- 2020/12/19 06:00 PMCR- 2020/02/01 CRDT- 2019/08/30 06:00 PHST- 2019/07/15 00:00 [received] PHST- 2019/08/27 00:00 [accepted] PHST- 2019/08/30 06:00 [pubmed] PHST- 2020/12/19 06:00 [medline] PHST- 2019/08/30 06:00 [entrez] PHST- 2020/02/01 00:00 [pmc-release] AID - BJBMS-20-78 [pii] AID - 10.17305/bjbms.2019.4359 [doi] PST - epublish SO - Bosn J Basic Med Sci. 2020 Feb 5;20(1):78-87. doi: 10.17305/bjbms.2019.4359.