ABSTRACT
Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.
ABSTRACT
BACKGROUND AND OBJECTIVE: Cervical cancer is an important health problem in our country. It is known that there are several risk factors for this neoplasm, and it has been suggested that cervical microbiome alterations could play a role in the development and progress of cancer. Bacterial vaginosis associated bacteria such as Atopobium vaginae and Gardnerella vaginalis has been suggested as potential risk factor for cervical lesions and cervical cancer. MATERIAL AND METHODS: DNA from 177 cervical scraping samples was studied: 104 belonged to women without cytological or colposcopic alterations and 73 samples from precursor lesions with previous human papillomavirus (HPV) infection history. All samples were screened for Atopobium vaginae, Gardnerella vaginalis and HPV by PCR. RESULTS: High HPV prevalence was found in precursor samples, and 30% of samples without lesions were positive for HPV. Virtually all samples contained sequences of both bacteria, and interestingly, there was not HPV association observed; these results could suggest that these microorganisms could be part of the cervical microbiome in Mexican population. CONCLUSIONS: The results obtained indicate that the bacteria analysed could be part of normal biome in Mexican women, suggesting a potential reconsideration of the pathogen role of these microorganisms.
Subject(s)
Actinobacteria/isolation & purification , Gardnerella vaginalis/isolation & purification , Papillomaviridae/isolation & purification , Papillomavirus Infections/complications , Uterine Cervical Neoplasms/microbiology , Vaginosis, Bacterial/complications , Actinobacteria/genetics , Coinfection/microbiology , Coinfection/virology , DNA, Bacterial/isolation & purification , DNA, Viral/isolation & purification , Female , Gardnerella vaginalis/genetics , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/microbiology , Humans , Menstrual Cycle , Mexico , Microbiota , Papillomaviridae/genetics , Papillomavirus Infections/virology , Precancerous Conditions/complications , Precancerous Conditions/microbiology , Risk Factors , Uterine Cervical Neoplasms/virology , Vaginosis, Bacterial/microbiologyABSTRACT
BORIS is a transcription factor aberrantly expressed in human cancers that can regulate the expression of estrogen receptors in endometrial cancer and breast cancer. We evaluated the expression of BORIS and the estrogen receptors alpha (ER-α) and beta (ER-ß) in ten cell lines derived from cervical cancer using RT-PCR and Western-blot. We also evaluated 54 cervical tissues: normal epithelia, low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL), and invasive squamous carcinomas (SC) using immunohistochemistry. In the cell lines, BORIS mRNA and protein expressions are associated with ER-ß expression but not with ER-α expression. In the normal cervical epithelium, ER-α and ER-ß were expressed but the BORIS protein was not detected. In the LSIL samples, BORIS, ER-α and ER-ß were expressed; however, in the HSIL samples, only the BORIS and ER-ß expressions were detected, but ER-α expression was minimal or null. In the SC, only BORIS and ER-ß were detected. In summary, the results show that the expressions of BORIS and ER-ß increase while the expression of ER-α decreases according to the severity of the lesions. These results suggest synergistic roles for BORIS and ER-ß during cervical cancer progression with a possible regulation of the estrogen receptors by BORIS in the development of cervical cancer; however, more detailed studies are needed to confirm this suggestion and to determine the precise role of BORIS in cervical cancer.