Dynamic analysis of circulating tumor <scp>DNA</scp> to predict prognosis and monitor therapeutic response in metastatic relapsed cervical cancer

Tian, Xiaoyuan; Ge, Dongcen; Zhang, Feng; Zhang, Bocheng; Bai, Wanting; Xu, Xiaoying; Li, Zongjuan; Cao, Ying; Li, Peiying; Zou, Kun; Zou, Lijuan

doi:10.1002/ijc.33362

Cited by 17 publications

(13 citation statements)

References 53 publications

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“…To date, these have mainly involved the analysis of tumor-specific mutations. An analysis of two phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations by digital droplet PCR yielded a sensitivity of 22.2% [ 38 ]; further analyses by next generation sequencing (NGS) yielded sensitivities ranging between 31–35% for different mutations [ 39 ]. In another study, not correcting for possible clonal hematopoiesis mutation rates, up to 83% was reported [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients

Leffers

Herbst

Kropidlowski

et al. 2022

Cancers

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Cervical cancer is the fourth most common cancer in women, which is associated in >95% with a high-risk human papillomavirus (HPV) infection. Methylation of specific genes has been closely associated with the progress of cervical high-grade dysplastic lesions to invasive carcinomas. Therefore, DNA methylation has been proposed as a triage for women infected with high-risk HPV. Methylation analyses of cervical cancer tissue have shown that cell adhesion molecule 1 (CADM1) and myelin and lymphocyte protein (MAL) methylation are present in over 90% of all cervical high-grade neoplasias and invasive cervical cancers. Here, we established a liquid biopsy-based assay to detect MAL and CADM1 methylation in cell free (cf)DNA of cervical cancer. Methylation of the target gene was validated on bisulfite converted smear-DNA from cervical dysplasia patients and afterward applied to cfDNA using quantitative real-time PCR. In 52 smears, a combined analysis of CADM1 and/or MAL (CADM1/MAL) showed methylation in 86.5% of the cases. In cfDNA samples of 24 cervical cancer patients, CADM1/MAL methylation was detected in 83.3% of the cases. CADM1/MAL methylation was detected already in 81.8% of stage I-II patients showing the high sensitivity of this liquid biopsy assay. In combination with a specificity of 95.5% towards healthy donors (HD) and an area under the curve (AUC) of 0.872 in the receiver operating characteristic (ROC) analysis, CADM1/MAL cfDNA methylation detection might represent a novel and promising liquid biopsy marker in cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients

Leffers

Herbst

Kropidlowski

et al. 2022

Cancers

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“…Despite the small sample size, which limited statistical considerations, the study highlighted that AFD value tended to decrease in CC patients after treatment (surgery, chemotherapy, radiotherapy, or multimodal approaches) in parallel with tumor size while, when remaining steadily high, it did correlate with disease progression and metastasis onset. In addition, in patients with low baseline AFD, a subsequent increase was suggestive of relapse [51].…”

Section: Circulating Cell-free Dna (Ccfdna)mentioning

confidence: 99%

Liquid Biopsy in Cervical Cancer: Hopes and Pitfalls

Cafforio

Palmirotta

Lovero

et al. 2021

Cancers

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Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main cause of CC, as well as in the access and quality of services for CC prevention and diagnosis. At present, the most diffused screening and diagnostic tools for CC are Papanicolaou test and the more sensitive HPV-DNA test, even if both methods require gynecological practices whose acceptance relies on the woman’s cultural and religious background. An alternative (or complimentary) tool for CC screening, diagnosis, and follow-up might be represented by liquid biopsy. Here, we summarize the main methodologies developed in this context, including circulating tumor cell detection and isolation, cell tumor DNA sequencing, coding and non-coding RNA detection, and exosomal miRNA identification. Moreover, the pros and cons of each method are discussed, and their potential applications in diagnosis and prognosis of CC, as well as their role in treatment monitoring, are explored. In conclusion, it is evident that despite many advances obtained in this field, further effort is needed to validate and standardize the proposed methodologies before any clinical use.

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“…Seven other studies using NGS approaches have been recently published [ 69 – 75 ]. Lee et al designed an NGS panel of 24 genes associated with cervical cancer.…”

Section: Ctdna Mutation Analyses In Lb Of Cin and Cervical Cancermentioning

confidence: 99%

“…Mutations in five genes ( PIK3CA , BRAF , GNA11 , FBXW7 and CDH1 ) correlated with a significantly shorter progression-free survival (PFS; p = 0.005) and OS ( p = 0.007) in the metastatic patient cohort. Importantly, the authors show that longitudinal monitoring with ctDNA in LB samples can provide both predictive and prognostic information during treatment [ 75 ]. A CAPP-Seq-based NGS approach (197 gene panel) was also used in a small study [ 69 ] including four cervical cancer patients.…”

Section: Ctdna Mutation Analyses In Lb Of Cin and Cervical Cancermentioning

confidence: 99%

Clinical applications and utility of cell-free DNA-based liquid biopsy analyses in cervical cancer and its precursor lesions

et al. 2022

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Human papilloma virus (HPV) is an infectious carcinogenic agent. Nearly all cervical cancers are positive for one of the high-risk HPV subtypes. Although the introduction of the HPV vaccines in many countries have shown tremendous positive effects on the incidence of both cervical intraepithelial lesions (CIN) and invasive cancer, the large majority of females worldwide are still not vaccinated. Patients with diagnosed high-grade CIN need a lifelong close monitoring of possible relapse or development of invasive cancer. Different blood-based liquid biopsy approaches have shown great promise as an easily obtainable minimally invasive tool for early detection and monitoring of disease. Among the different liquid biopsy approaches the clinical relevance of cell-free DNA (cfDNA) in cervical cancer has been best investigated. In cervical cancer, the DNA fragments can be of both, human as well as viral origin. Thus, the mutation and methylation status of genes related to carcinogenesis as well as the HPV status can be analysed in plasma from cervical cancer patients. This review describes recent advances in different cfDNA approaches for early detection and monitoring of cervical cancer and its precursor lesions.

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Dynamic analysis of circulating tumor DNA to predict prognosis and monitor therapeutic response in metastatic relapsed cervical cancer

Cited by 17 publications

References 53 publications

Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients

Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients

Liquid Biopsy in Cervical Cancer: Hopes and Pitfalls

Clinical applications and utility of cell-free DNA-based liquid biopsy analyses in cervical cancer and its precursor lesions

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