scholarly journals The Role of the Cervicovaginal and Gut Microbiome in Cervical Intraepithelial Neoplasia and Cervical Cancer

2020 ◽  
Author(s):  
Travis T. Sims ◽  
Lauren E. Colbert ◽  
Ann H. Klopp
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Therapeutic Response ◽  
Critical Role ◽  
Intraepithelial Neoplasia ◽  
Ongoing Research ◽  
Papilloma Virus

ABSTRACT The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.

Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection

MicroRNA ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 110-115 ◽  
Author(s):  
Sara Zamani ◽  
Amir Sohrabi ◽  
Seyed Masoud Hosseini ◽  
Marjan Rahnamaye-Farzami ◽  
Abolfazl Akbari
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Invasive Cervical Cancer ◽  
Hpv Infection ◽  
Micro Rna ◽  
Internal Reference ◽  
Specific Primers ◽  
Papilloma Virus

Background:Early diagnosis is an important factor to improve the survival of Invasive Cervical Cancer (ICC) patients. Molecular biomarkers such as micro RNA (miRNA) can be used in the early detection of ICC. The expression of miR-21 and miR-29a are deregulated in many types of human cancers.Objective:The aim of this study was to investigate the differences in miR-21 and miR-29a expression patterns in the Human Papilloma Virus (HPV) infection and various grades of cervical cancer among Iranian women.Methods:Small RNAs were extracted from positive for HPV, cervical cancer and healthy samples from 43, 50 and 46 individuals, respectively. Expression levels of miR-21 and miR-29a were analyzed by SYBR Green real-time RT-PCR using specific primers, and 5s rRNA as the internal reference gene.Results:Results have shown a significant increase in miR-21 and decrease in miR-29 in cancerous samples in comparison with the control groups (P < 0.0001).Conclusion:This study illustrated that miR-21 and miR-29a could be operated as an oncogene and tumor-suppressor in cervical cancer progression. More studies are needed to demonstrate the role of miR-21 and miR-29a as potential biomarkers for the diagnosis of cervical cancer in future investigations.

scholarly journals Upregulation of Translationally Controlled Tumor Protein Is Associated With Cervical Cancer Progression

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyu Zhu ◽  
Ji Ren ◽  
Dianqin Xu ◽  
Di Cheng ◽  
Wei Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cell Lines ◽  
Cancer Progression ◽  
Protein Interactions ◽  
Intraepithelial Neoplasia ◽  
Cancer Tissue ◽  
Functional Protein ◽  
Translationally Controlled Tumor Protein ◽  
Potential Biomarker

Outside a few affluent countries with adequate vaccination and screening coverage, cervical cancer remains the leading cause of cancer-related deaths in women in many countries. Currently, a major problem is that a substantial proportion of patients are already at an advanced cancer stage when diagnosed. There is increasing evidence that indicates the involvement of translationally controlled tumor protein 1 (TPT1) overexpression in cancer development, but little is known about its implication in cervical cancer. We assessed the levels of TPT1 in surgical tissue and sera of patients with cervicitis, cervical intraepithelial neoplasia III, and cervical cancer, as well as in normal and cancerous cervical cell lines. Gene sets, pathways, and functional protein interactions associated with TPT1 were identified using the TCGA data cohort of cervical cancer. We found that the TPT1 expression was significantly increased in cervical cancer tissue compared to all nonmalignant cervical tissues, including samples of cervicitis, cervical intraepithelial neoplasia III, and normal controls. Serum level of TPT1 was also increased in cervical cancer patients compared to healthy subjects. Furthermore, elevated TPT1 expression was significantly correlated with lymph node metastasis and a low differentiation degree of the cancer. In the cancerous tissues and cell lines, selective markers of PI3K/AKT/mTOR pathway over-activation, apoptosis repression, and EMT were detected, and their interaction with TPT1 was supported by biometrics analyses. Our results, for the first time, demonstrate a strong correlation of upregulated TPT1 expression with cervical cancer progression, suggesting that TPT1 might provide a potential biomarker for cervical cancer progression.

scholarly journals MicroRNA Biomarkers of High-Grade Cervical Intraepithelial Neoplasia in Liquid Biopsy

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Rhafaela L. Causin ◽  
Luciane S. da Silva ◽  
Adriane F. Evangelista ◽  
Letícia F. Leal ◽  
Karen C. B. Souza ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Mirna Expression ◽  
Liquid Biopsy ◽  
Intraepithelial Neoplasia ◽  
Differentially Expressed ◽  
Molecular Pathways ◽  
Precursor Lesions ◽  
Nanostring Technology

New prevention strategies are needed to detect cervical intraepithelial neoplasia (CIN). The microRNA expression analysis has already been reported as molecular biomarkers in the early detection of cervical cancer (CC) through minimally invasive samples, such as liquid biopsy, obtained through collection using liquid-based cytology (LBC). In this study, we aimed to identify molecular signatures of microRNAs in cervical precursor lesions from LBC cervical and the molecular pathways potentially associated with the CC progression. We analyzed 31 LBC cervical samples from women who underwent colposcopy. These samples were divided into two groups: the first group was composed of samples without precursor lesions of CC, considering the control group, referred to as healthy female subjects (HFS; n = 11 ). The second group corresponded to women diagnosed with cervical interepithelial neoplasia grade 3 (CIN 3; n = 20 ). We performed microRNA and gene expression profiling using the nCounter® miRNA Expression Assays (NanoString Technology) and PanCancer Pathways (NanoString Technology), respectively. A microRNA target prediction was performed by mirDIP, and molecular pathway interaction was constructed using Cytoscape. Bidirectional in silico analyses and Pearson’s correlation were performed for associated the relation between genes, and miRNAs differentially expressed related cervical cancer progression were performed. We found that the expression of nine microRNAs was significantly higher, two were downregulated (miR-381-3p and miR-4531), and seven miRNAs were upregulated (miR-205-5p, miR-130a-3p, miR-3136-3p, miR-128-2-5p, let-7f-5p, miR-202-3p, and miR-323a-5p) in CIN 3 ( fold   change ≥ 2 and p ≤ 0.05 ). The miRNA expression patterns were independent of hr-HPV infection. We identified four miRNAs (miR-205-5p, miR-130a-3p, miR-4531, and miR-381-3p) that could be used as biomarkers for CIN 3 in LBC samples through multiple logistic regression analyses. We found 16 genes differentially expressed between CIN 3 and HSF samples ( fold   change ≥ 2 and p ≤ 0.05 ). We found the correlation between miR-130a-3p and CCND1( R = − 0.52 ; p = 0.0029 ), miR-205-5p and EGFR ( R = 0.53 ; p = 0.0021 ), and miR-4531 and SMAD2 ( R = − 0.54 ; p = 0.0016 ). In addition, we demonstrated the most significant pathways of the targets associated with cervical cancer progression (FDR-corrected p < 0.001 ). This study demonstrated that miRNA biomarkers may distinguish healthy cervix and CIN 3 and regulate important molecular pathways of carcinogenesis.

scholarly journals Expression and role of nestin in human cervical intraepithelial neoplasia and cervical cancer

2012 ◽  
Vol 41 (2) ◽  
pp. 441-448 ◽  
Author(s):  
ATSUKI SATO ◽  
TOSHIYUKI ISHIWATA ◽  
YOKO MATSUDA ◽  
TETSUSHI YAMAMOTO ◽  
HIROBUMI ASAKURA ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia

scholarly journals The Trained Sniffer Dog Could Accurately Detect the Urine Samples from the Patients with Cervical Cancer, and Even Cervical Intraepithelial Neoplasia Grade 3: A Pilot Study

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3291
Author(s):  
Akihito Yamamoto ◽  
Seiryu Kamoi ◽  
Keisuke Kurose ◽  
Marie Ito ◽  
Toshiyuki Takeshita ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patient ◽  
Healthy Volunteers ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Intraepithelial Neoplasia ◽  
Urine Samples ◽  
Premalignant Lesions ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Grade 3

(1) Background: Previous reports have indicated that cancers of the stomach, lung, and pancreas can be detected by dog sniffing, but results have been varied. Here, a highly trained dog was used to determine whether urine from patients with cervical premalignant lesions and malignant tumors have a cancer-specific scent. (2) Methods: A total of 195 urine samples were collected from patients with cervical cancer, cervical intraepithelial neoplasia grade 3 (CIN3), benign uterine diseases, and healthy volunteers. Each test was performed using one urine sample from a cancer patient and four samples from different controls. Each of the five urine samples was placed in a separate box. When the cancer sniffing dog stopped and sat in front of the box with a sample from a cancer patient, the test was considered as positive. (3) Results: 83 patients with cervical cancer (34 cases of cervical cancer and 49 cases of cervical intraepithelial neoplasia grade 3), 49 patients with uterine benign diseases, and 63 healthy volunteers were enrolled, and their urine samples were collected. In 83 times out of 83 runs in a double-blind test, the trained dog could correctly identify urine samples of cervical cancer patients. (4) Conclusion: A trained dog could accurately distinguish the urine of all patients with cervical cancer or CIN3, regardless of the degree of cancer progression.

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