scholarly journals LC/MS-Based Polar Metabolite Profiling Identified Unique Biomarker Signatures for Cervical Cancer and Cervical Intraepithelial Neoplasia Using Global and Targeted Metabolomics

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 511 ◽  
Author(s):  
Imran Khan ◽  
Miso Nam ◽  
Minji Kwon ◽  
Sang-soo Seo ◽  
Sunhee Jung ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Metabolic Pathways ◽  
Multivariate Logistic Regression Analysis ◽  
Intraepithelial Neoplasia ◽  
Cervical Carcinogenesis ◽  
Cervical Cancers ◽  
Hpv Status ◽  
Increased Risk ◽  
Risk Of Cancer

Cervical cancer remains one of the most prevalent cancers among females worldwide. Therefore, it is important to discover new biomarkers for early diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer, preferably non-invasive ones. In the present study, we aimed to identify unique metabolic signatures for CINs and cervical cancers using global and targeted metabolomic profiling. Plasma samples (69 normal, 55 CIN1, 42 CIN2/3, and 60 cervical cancer) were examined by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS) coupled with multivariate statistical analysis. Metabolic pathways were analyzed using the integrated web-based tool MetaboAnalyst. A multivariate logistic regression analysis was conducted to evaluate the combined association of metabolites and human papillomavirus (HPV) status with the risk of cervical carcinogenesis. A total of 28 metabolites exhibiting discriminating levels among normal, CIN, and cervical cancer patients (Kruskal–Wallis test p < 0.05) were identified in the global profiling analysis. The pathway analysis showed significantly altered alanine, aspartate, and glutamate metabolic pathways (FDR p-value < 0.05) in both the discovery and validation phases. Seven metabolites (AMP, aspartate, glutamate, hypoxanthine, lactate, proline, and pyroglutamate) were discriminated between CINs and cervical cancer versus normal (area under the curve (AUC) value > 0.8). The levels of these metabolites were significantly high in patients versus normal (p < 0.0001) and were associated with increased risk of developing CIN2/3 and cervical cancer. Additionally, elevated levels of the seven metabolites combined with positive HPV status were correlated with substantial risk of cancer progression. These results demonstrated that metabolomics profiling is capable of distinguishing CINs and cervical cancers from normal and highlighted potential biomarkers for the early detection of cervical carcinogenesis.

scholarly journals Association study of relationships of polymorphisms in the miR-21, miR-26b, miR-221/222 and miR-126 genes with cervical intraepithelial neoplasia and cervical cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia Yang ◽  
Zhiling Yan ◽  
Yingying Wang ◽  
Jinmei Xu ◽  
Rui Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Additive Model ◽  
Intraepithelial Neoplasia ◽  
Recessive Model ◽  
Cancer Development ◽  
Nucleotide Polymorphisms ◽  
Mirna Genes ◽  
Increased Risk ◽  
Cervical Cancer Development

Abstract Background miR-21, miR-26b, miR-221/222 and miR-126 play crucial roles in cervical cancer development. Studies have shown that polymorphisms in miRNA genes can affect miRNA expression, which might be associated with cancer development. Methods Ten single-nucleotide polymorphisms (SNPs) in the miR-21, miR-26b, miR-221/222 and miR-126 genes (rs1292037, rs13137 in miR-21; rs2227255, rs2227258 in miR-26b; rs2858061, rs34678647, rs2858060, rs2745709 in miR-221/222; rs2297537, rs2297538 in miR-126) were selected, and genotyped in a total of 2176 individuals, including 435 patients with cervical intraepithelial neoplasia (CIN), 743 patients with cervical cancer (CC) and 998 healthy persons using TaqMan assays, and their associations with CIN and CC were evaluated. Results Our results showed significant differences for the rs2297538 genotypes between the CIN and CC groups (P = 0.001). In addition, our results also showed significant differences for the rs2297537 alleles between the CIN and CC groups (P = 0.003), and the C allele of rs2297537 might be associated with a decreased risk of CC (OR = 0.72, 95%CI: 0.58–0.90). At the inheritance analysis, between the CIN and control groups, the T/T-T/C genotype in rs1292037 and A/A-A/T genotype in rs13137 might be associated with an increased risk of CIN in the recessive model (OR = 1.61, 95% CI: 1.17–2.20 and OR = 1.58, 95% CI: 1.15–2.15). In addition, the C/C-T/T genotype of rs2745709 might be associated with a decreased risk of CIN in the overdominant model (OR = 0.66, 95% CI: 0.52–0.82). Between, CIN and CC group, the T/T-C/C genotype in rs1292037 and A/A-T/T genotype in rs13137 might be associated with an increased risk of CC in the overdominant model (OR = 1.43, 95% CI: 1.12–1.81 and OR = 1.42, 95% CI: 1.12–1.80). The rs2297538 G/G-A/G genotype might be associated with an increased risk of CC in the recessive model (OR = 2.83, 95% CI: 1.52–5.25). The rs2297537 2C/C + C/G genotype might be associated with a decreased risk of CC (OR = 0.71, 95% CI: 0.57–0.89) in the log-additive model. The rs2745709 T/T-C/C genotype might be associated with an increased risk of CC (OR = 1.44, 95% CI: 1.13–1.83) in the overdominant model. Conclusion Our results indicate that rs2297538 and rs2297537 in miR-126, rs1292037 and rs13137 in miR-21, and rs2745709 in miR-221/222, may have important roles in the development of CIN or CC.

scholarly journals Associations of Dietary Glycemic Index, Glycemic Load and Carbohydrate with the Risk of Cervical Intraepithelial Neoplasia and Cervical Cancer: A Case-Control Study

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3742
Author(s):  
Sundara Raj Sreeja ◽  
Sang Soo Seo ◽  
Mi Kyung Kim
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Glycemic Index ◽  
Case Control Study ◽  
Glycemic Load ◽  
Intraepithelial Neoplasia ◽  
Case Control ◽  
Increased Risk ◽  
Dietary Glycemic Index ◽  
Control Study

Background: The association of dietary glycemic index (GI) and glycemic load (GL) with the risk of cervical cancer has never been investigated. Thus, we aimed to find evidence of any association of GI and GL with the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods: In this hospital-based case-control study, we included 1340 women (670 controls and 262, 187 and 221 patients with CIN1, CIN2/3, and cervical cancer, respectively) from the Korean human papillomavirus cohort study. Completed demographic questionnaires and semi-quantitative food-frequency questionnaires were collected. The association of dietary GI and GL with CIN and cervical cancer was estimated using a logistic regression model. Results: The multivariate odds ratios (OR) of the highest compared with the lowest quintile of GL for CIN1 were 2.8 (95% confidence interval (CI) = 1.33–5.88). Dietary GI and GL were not associated with CIN2/3 and cervical cancer. Stratified analyses by body mass index (BMI) indicated a positive association between GI and GL and CIN 1 risk among women with a BMI (in kg/m2) <23 (OR = 2.94; 95% CI = 1.32–6.53; p for trend = 0.031 for GI and OR = 3.15; 95% CI = 1.53–6.52; p for trend = 0.013 for GL), but not among those with a BMI of ≥23. A stratification analysis by menopausal status showed that the highest quintile of GI and GL was significantly associated with the risk of CIN1 (OR = 2.91; 95% CI = 1.43–5.96; p for trend = 0.005) (OR = 2.96; 95% CI = 1.53–5.69; p for trend = 0.023) among premenopausal women. Also, in HPV positive women, dietary GL showed significant CIN1 risk (OR = 2.61; 95% CI = 1.09–6.24; p for trend = 0.087). Conclusion: Our case-control study supports the hypothesized associations of dietary GI and GL with increased risk of CIN1. Thus, the consumption of low GI and GL foods plays a significant role in the prevention of cervical carcinogenesis.

scholarly journals Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study

BMJ ◽  
2007 ◽  
Vol 335 (7629) ◽  
pp. 1077 ◽  
Author(s):  
Björn Strander ◽  
Agneta Andersson-Ellström ◽  
Ian Milsom ◽  
Pär Sparén
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Female Population ◽  
Increased Risk ◽  
Grade 3 ◽  
Log Linear

Objective To study the long term risk of invasive cancer of the cervix or vagina after treatment for cervical intraepithelial neoplasia grade 3. Design Prospective cohort study. Setting Swedish cancer registry. Participants All women in Sweden with severe dysplasia or cervical carcinoma in situ (equivalent to cervical intraepithelial neoplasia grade 3) treated during 1958-2002 (n=132 493) contributing 2 315 724 woman years. Main outcome measures Standardised incidence ratios with risk of cancer in the Swedish general female population as reference, and relative risks in multivariable log-linear regression model, with internal references. Results Women with previous cervical intraepithelial neoplasia grade 3 had an increased risk of invasive cervical cancer compared with the general female population (standardised incidence ratio 2.34, 95% confidence interval 2.18 to 2.50). The increased risk showed a decreasing trend with time since diagnosis for women treated later than 1970 but the risk was still increased after 25 years. An effect of age was found, with an accentuated increase in risk for women aged more than 50. The excess risk for cervical cancer associated with previous cervical intraepithelial neoplasia grade 3 has steadily increased since 1958. For vaginal cancer the standardised incidence ratio was 6.82 (5.61 to 8.21) but this decreased to 2.65 after 25 years. Adjustments in the multivariable log-linear regression model did not substantially alter these results. Conclusions Women previously treated for cervical intraepithelial neoplasia grade 3 are at an increased risk of developing invasive cervical cancer and vaginal cancer. This risk has increased since the 1960s and is accentuated in women aged more than 50. The risk is still increased 25 years after treatment.

scholarly journals Compositional and Functional Differences between Microbiota and Cervical Carcinogenesis as Identified by Shotgun Metagenomic Sequencing

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 309 ◽  
Author(s):  
Minji Kwon ◽  
Sang-Soo Seo ◽  
Mi Kim ◽  
Dong Lee ◽  
Myoung Lim
Keyword(s):  
Cervical Cancer ◽  
Defense Mechanisms ◽  
Intraepithelial Neoplasia ◽  
Normal Subjects ◽  
Metagenomic Sequencing ◽  
Cervical Carcinogenesis ◽  
Cervical Lesions ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing ◽  
Increased Risk

Recent studies have reported the potential role of microbiomes in cervical disease. However, little is known about the microbiome composition and function in cervical carcinogenesis. We aimed to identify the compositional and functional alterations of cervical microbiomes in cases of cervical carcinogenesis of Korean women using shotgun metagenomic sequencing. In this study, using shotgun sequencing, we sequenced the cervical metagenomes of cervical intraneoplasia 2/3 (n = 17), cervical cancer (n = 12), and normal controls (n = 18) to identify the microbial abundances and enriched metabolic functions in cervical metagenomes. At the genus level, the microbiota of cervical cancer were differentially enriched with genera Alkaliphilus, Pseudothermotoga, and Wolbachia. Cervical intraepithelial neoplasia (CIN) 2/3 were enriched with Lactobacillus, Staphylococcus, and Candidatus Endolissoclinum. The normal group was enriched with Pseudoalteromonas and Psychrobacter. Further characterization of the functionalities of the metagenomes may suggest that six Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) that are involved in 10 pathways are associated with an increased risk of CIN2/3 and cervical cancer. Specifically, cervical metagenomes were enriched in the course of peptidoglycan synthesis and depleted by dioxin degradation and 4-oxalocrotonate tautomerase. The Cluster of Orthologous Groups (COG) category ‘Defense mechanisms’ was depleted in cervical cancer patients. Our findings based on shotgun metagenomic sequencing suggest that cervical microbiome community compositions and their metagenomics profiles differed between cervical lesions and normal subjects. Future studies should have larger sample sizes and/or aggregate their results to have sufficient power to detect reproducible and significant associations.

scholarly journals Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mario Preti ◽  
Stefano Rosso ◽  
Leonardo Micheletti ◽  
Carola Libero ◽  
Irene Sobrato ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Significant Risk ◽  
Intraepithelial Neoplasia ◽  
Second Primary ◽  
Standardized Incidence Ratio ◽  
Screening Programs ◽  
Cervical Cancers ◽  
Increased Risk ◽  
Cervical Tumors ◽  
Cervical Human Papillomavirus

Abstract Background The aim was to estimate the risk of subsequent extra-cervical Human Papillomavirus (HPV) related cancer in patients surgically treated for high grade cervical intraepithelial neoplasia (CIN 2–3). This is the first study in Italy investigating the occurrence of extra-cervical tumors in this cohort of patients. Methods 3184 patients surgically treated for CIN2–3 since 1992 at the Department of Surgical Sciences of University of Torino were considered. The risk of HPV-related cancer was calculated as Standardized Incidence Ratio (SIR), using as expected values tumour age specific incidence of resident population. Results 173 second primary cancer (SCPs) were identified. SIR to develop cancer after treatment for CIN2–3 was 2.2 (CI 95% 1.89–2.50). Among these occurrences, 10 are in HPV related sites: 1 anus (SIR = 1.8; 0.04–10.0), 3 vagina (SIR = 12.4; 2.56–36.3), 1 vulva (SIR = 1.7; 0.04–9.59), 5 oropharynx (SIR = 8.5; 2.76–19.8). Significant risk has been also recorded for pulmonary (SIR = 3.1; 0.70–5.27) and bladder (SIR = 4.05; 1.10–10.56), with smoking as possible cofactor. We also found increased risk for breast (SIR = 2.4; 2.07–2.84) and ovarian cancers (SIR = 2.1; 1.13–3.49), probably due to an higher adherence to spontaneous and programmed screening programs. Conclusions Our study supports the hypothesis of an increased risk of HPV-related tumours for CIN treated patients, mostly for CIN3. It is conceivable the need of early diagnosis for these cancers in this higher-risk populations.

Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions.

1997 ◽  
Vol 15 (5) ◽  
pp. 1932-1937 ◽  
Author(s):  
C C Pao ◽  
C J Tseng ◽  
C Y Lin ◽  
F P Yang ◽  
J J Hor ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Patients ◽  
Dna Sequences ◽  
Intraepithelial Neoplasia ◽  
Telomerase Activity ◽  
Progressive Increase ◽  
Telomere Repeat ◽  
Cervical Cancers ◽  
Human Cervical Cancer

PURPOSE Telomeres are tandem arrays of repeated DNA sequences located at the ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase. Loss of telomeric DNA may play an important role in the development of human cancers. However, very little is known about the status of telomerase during human cervical cancer development. PATIENTS AND METHODS Telomerase activity was measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer patients and normal cervical tissues from 11 control individuals also were examined for the presence of telomerase activity. RESULTS Twenty two of the 24 (91.7%) cervical cancer specimens and the single CIS tissue were strongly positive for telomerase activity. Relatively weak but distinctive telomerase activity also was detectable in one of four CIN-I (25%), two of eight CIN-II (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity was not found in the 24 corresponding nontumor cervical tissues from the same cervical cancer patients and the 11 normal cervical tissues from control individuals. CONCLUSION The majority of cervical cancers contain strong telomerase activity. Significant proportions of noncancerous CIN tissues also contain telomerase activity, although weaker than that in cervical cancer. It seems that there is a progressive increase of telomerase activity in association with an increased degree of cervical malignancy. These results seem to suggest that the expression of telomerase may play a crucial role in cervical cancer carcinogenesis.

scholarly journals Antioxidant and inflammatory potential of diet among women at risk of cervical cancer: findings from a cross-sectional study in Italy

2021 ◽  
pp. 1-23
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Aurora Scalisi ◽  
Antonella Agodi
Keyword(s):  
Cervical Cancer ◽  
Smoking Status ◽  
Intraepithelial Neoplasia ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Papanicolaou Test ◽  
Cross Sectional ◽  
Inflammatory Index ◽  
Hpv Status ◽  
Increased Risk

Abstract Objective To evaluate the association of Composite Dietary Antioxidant Index (CDAI) and Dietary Inflammatory Index (DII) with the prevalence of high-grade cervical intraepithelial neoplasia (CIN). Design A cross-sectional study was conducted on women with abnormal Papanicolaou test, who underwent high-risk HPV screening and histological test through colposcopy. Dietary data were collected using a Food Frequency Questionnaire and used to assess both CDAI and DII. Setting Women were recruited from 2012 to 2015 at the Cervical Cancer Screening Unit of the “Azienda Sanitaria Provinciale” of Catania (Italy). Participants The study included 539 women with a mean age of 40.2 years, who were classified as cases (n=127 with CIN2 or more severe lesions) and controls (n= 412 with normal cervical epithelium or CIN1). Results Although we observed a lower proportion of HPV-positive women among those with higher CDAI (p<0.001), the index was not associated with the diagnosis of CIN2 or more severe lesions. By contrast, women with medium or high DII showed higher odds to be diagnosed with CIN2 or more severe lesions than those with low DII (OR=2.15; 95%CI=1.11–4.17; p=0.024 and OR=3.14; 95%CI=1.50–6.56; p=0.002, respectively), after adjusting for age, HPV status, educational level, body mass index, smoking status, parity, use of oral contraceptives and supplements. Conclusions Our findings suggested that a pro-inflammatory diet might be associated with an increased risk of CIN2 and more severe lesions. However, further prospective studies should be encouraged to support this evidence.

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