Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

Abstract Background: Although human papillomavirus (HPV) infection has been recognized as the cause of cervical cancer in over 99% of cases, only a minority of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown.Methods: In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models.Results: HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant.Conclusions: In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

10.21203/rs.2.16632/v5 ◽

2020 ◽

Author(s):

Wei Sun ◽

Xueyun Qin ◽

Jing Zhou ◽

Mingjing Xu ◽

Zhangyan Lyu ◽

...

Keyword(s):

Cervical Cancer ◽

Logistic Regression ◽

Mitochondrial Dna ◽

Copy Number ◽

Wald Test ◽

Hpv Infection ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Exfoliated Cells ◽

Hpv Types

Abstract Background Although human papillomavirus (HPV) infection has been recognized as the cause of cervical cancer in over 99% of cases, only a minority of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown.Methods In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models.Results HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant.Conclusions In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

10.21203/rs.2.16632/v3 ◽

2020 ◽

Author(s):

Wei Sun ◽

Xueyun Qin ◽

Jing Zhou ◽

Mingjing Xu ◽

Zhangyan Lyu ◽

...

Keyword(s):

Cervical Cancer ◽

Logistic Regression ◽

Mitochondrial Dna ◽

Copy Number ◽

Wald Test ◽

Hpv Infection ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Exfoliated Cells ◽

Hpv Types

Abstract Background Although human papillomavirus (HPV) infection has been recognized as the major cause of cervical cancer, only a minority of HPV-infected women develop this malignancy. An increasing amount of evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may c ontribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown. Methods In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assay s , and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models. Results HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls ( P = 0.03). After adjustment for age and HPV types , the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed ( P trend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant. Conclusions Increased mtCN in cervical exfoliated cells is associated with cervical cancer after HPV infection, suggesting a potential role of mtCN in cervical carcinogenesis.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

10.21203/rs.2.16632/v1 ◽

2019 ◽

Author(s):

Wei Sun ◽

Xueyun Qin ◽

Jing Zhou ◽

Mingjing Xu ◽

Zhangyan Lyu ◽

...

Keyword(s):

Cervical Cancer ◽

Mitochondrial Dna ◽

Copy Number ◽

Hpv Infection ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Exfoliated Cells ◽

Hpv Types ◽

Dose Response Effect ◽

And Control

Abstract Background: Although human papillomavirus (HPV) infection has been recognized as the major cause of cervical cancer, only a minority of HPV-infected women develop this malignancy. An increasing amount of evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown. Methods: In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls ( P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed ( P trend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant. Conclusions: Increased mtCN in cervical exfoliated cells is associated with cervical cancer after HPV infection. Our study provides a basis for future studies to determine the potential of mtCN as a novel biomarker in cervical cancer screening.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

BMC Women s Health ◽

10.1186/s12905-020-01001-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Wei Sun ◽

Xueyun Qin ◽

Jing Zhou ◽

Mingjing Xu ◽

Zhangyan Lyu ◽

...

Keyword(s):

Cervical Cancer ◽

Mitochondrial Dna ◽

Copy Number ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Exfoliated Cells

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P–217 The mitochondrial DNA copy number of cumulus granulosa cells is associated with the symmetry of cleavage embryo but not blastocyst quality

Human Reproduction ◽

10.1093/humrep/deab130.216 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Y Ji ◽

L Hu

Keyword(s):

Logistic Regression ◽

Mitochondrial Dna ◽

Granulosa Cells ◽

Copy Number ◽

Poor Quality ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Fair Poor ◽

The Relationship

Abstract Study question To study the relationship between mitochondrial DNA copy number of cumulus granulosa cells (CGCs-mtDNA) and the quality of early embryos. Summary answer CGCs-mtDNA was related to the symmetry of cleavage. However, CGCs-mtDNA was not associated with fertilization, blastocysts quality, or blastocysts euploidy. What is known already The potential of early embryonic development mainly depends on the quality of oocytes to a large extent. Mitochondria of CGCs are directly involved in the establishment of oocytes capacitation during oocytes maturation and development. Study design, size, duration This is a retrospective study from December 2018 to January 2019, involving a total of 283 CGCs surrounding Metaphase II oocytes from 49 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) at the Reproductive and Genetic Hospital of CITIC-Xiangya. Participants/materials, setting, methods We used the TaqMan probes to quantitatively detect mitochondrial DNA copy number of per CGCs by quantitative PCR in mitochondrial genes (MT-ND1 and MT-CO1) and a nuclear gene (β-globin). Besides, according to the nature of the dependent variable, the binary logistic regression model and the logistic regression analysis model of ordered multi-classification were used for multivariate statistical analysis. Main results and the role of chance The CGCs-mtDNA corresponding to fertilized eggs was not different from that of unfertilized eggs in MT-ND1 gene and MT-CO1 gene (MT-ND1: fertilized vs. unfertilized, 600±337 vs. 604±367, P = 0.593; MT-CO1: fertilized vs. unfertilized, 1336±531 vs. 1329±478, P = 0.938). Interestingly, we found that the CGCs-mtDNA of D3 embryos with good quality was statistically higher than that of D3 embryos with fair or poor quality for MT-ND1 gene and MT-CO1 gene (MT-ND1: good quality vs. fair/poor quality, 803±627 vs. 587±307, P = 0.028; MT-CO1: good quality vs. fair/poor quality, 1682±554 vs. 1374±702, P = 0.025). Moreover, the CGCs-mtDNA corresponding to D3 embryos with even cleavage was higher than that of D3 embryos with uneven cleavage (MT-ND1: even cleavage vs. uneven cleavage, 803±627 vs. 590±309, P = 0.036; MT-CO1: even cleavage vs. uneven cleavage, 1562±552 vs. 1316±525, P = 0.037). Besides, we investigated the difference among the CGCs-mtDNA in blastocysts with the good quality, blastocysts with fair or poor quality, and the developmental blocked embryos before the blastocyst stage. But we didn’t found any difference among the above three groups (MT-ND1: P = 0.531; MT-CO1: P = 0.609). In the study of the relationship between CGCs-mtDNA and blastocysts euploidy, we got similar results (MT-ND1: P = 0.602; MT-CO1: P = 0.570). Limitations, reasons for caution The sample size of this study was relatively small. Wider implications of the findings: Although the sample size of this study is limited, our results indicated the importance of mitochondria in CGCs in early embryo development, especially in the first three days. The investigation of mitochondrial function in CGCs may shed light on the mechanism of CGCs-oocyte crosstalk. Trial registration number LL-SC–2019–005

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