Biomarkers of Gynecological Cancers

Chiyoda, Tatsuyuki; Dozen, Ai; Saotome, Keiko; Nanki, Yoshiko; Aoki, Daisuke

doi:10.1007/978-981-13-7295-7_13

Cited by 2 publications

(2 citation statements)

References 102 publications

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“…Debulking surgery with platinum-combination chemotherapy is usually administered to patients, irrespective of the histological subtypes, namely high-grade serous (HGSC), endometrioid (EM), clear cell (CCC), and mucinous carcinoma. HGSC comprises 70–80% of all ovarian cancer cases and is characterised by TP53 mutation, with many chromosomal aberrations 6 . EM and CCC are endometriosis-associated ovarian cancers that frequently harbour the ARID1A mutation.…”

Section: Introductionmentioning

confidence: 99%

Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing

Nanki

Chiyoda

Hirasawa

et al. 2020

Sci Rep

Self Cite

103

118

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The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in < 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1-73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs. Patient-derived tumour organoids have become important preclinical model systems in both cancer research and clinical settings 1. In contrast to patient-derived xenograft (PDX) mouse models that need a large amount of surgical specimen and 4-8 months for development 2 , organoids can be cultured from patient materials and can be expanded with high efficiency in a relatively short period (typically < 1 month). Organoids from mouse intestine, as well as from various other mouse and human tissues, including the colon, stomach, liver, lung, prostate, and pancreas, have been established 3,4. Patient-derived tumour organoids have also been generated from the colon, pancreas, prostate, breast, gastric, lung, oesophageal, bladder, ovarian, kidney, and liver tumour tissues 1. Organoids maintain the key genetic and phenotypic features of primary tumours, thereby, enabling their use in a broad range of applications, such drug development and identification of the best therapeutic regimen for each patient. Ovarian cancer is a devastating disease, with 295,000 new patients and 185,000 deaths each year, worldwide 5. The relative 5-year survival rate is 47% and has not apparently increased in the last 40 years. Debulking surgery with platinum-combination chemotherapy is usually administered to patients, irrespective of the histological

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Section: Introductionmentioning

confidence: 99%

Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing

Nanki

Chiyoda

Hirasawa

et al. 2020

Sci Rep

Self Cite

103

118

View full text Add to dashboard Cite

show abstract

“…At present, standard methods for screening ovarian cancer are ultrasonography and the serum carbohydrate antigen 125 (CA125) [4,5]. CA125 remains the best serum tumor marker for ovarian cancer, nevertheless increased serum CA125 levels may give false positive results in benign gynecological conditions and other cancers [5][6][7]. Thus, identifying biomarkers with higher sensitivity and specificity for early detection and dynamic disease monitoring remains a major unmet clinical need for ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Identifying Potential Markers for Monitoring Progression to Ovarian Cancer Using Plasma Label-free Proteomics

Wang

Xie

Xia

et al. 2019

Preprint

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PurposeCancer antigen 125 (CA125) is considered to have high sensitivity but poor specificity for ovarian cancer. New biomarkers utilized to early detect and monitor the progression of ovarian cancer patients are critically needed. Methods A total of 80 patients including 16 early stage, and matched with 17 late stage, 23 benign ovarian tumor (BOT) and 24 uterine fibroid (UF) patients were utilized to perform plasma proteomics analysis using isobaric tag for relative and absolute quantitation (iTRAQ) method to identify differential diagnostic proteins of ovarian cancer patients. A validation set of 9 early stage, 11 late stage, 17 BOT and 16 UF collected by an independent cohort of samples with the same matching principles was examined to confirm the expressed levels of differential expression proteins by ELISA analysis. Results CRP and ARHGEF 11 were identified as potential diagnostic biomarkers of ovarian cancer. Results of area under the curve (AUC) analysis suggested that combination of diagnostic proteins and CA125 achieved a much higher diagnostic accuracy compared with CA125 alone (AUC values: 0.98 versus 0.80), especially improved the specificity (0.97 versus 0.77). In addition, elevated plasma CRP levels were associated with increased risk of ovarian cancer. Conclusions Current study found that plasma protein CRP was an indicator for monitoring the progression of ovarian cancer. Combination of plasma protein biomarkers with CA125 could be utilized to early diagnose of ovarian cancer patients. Keywords ovarian cancer, proteomics, diagnosis, progression, CRP

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Biomarkers of Gynecological Cancers

Cited by 2 publications

References 102 publications

Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing

Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing

Identifying Potential Markers for Monitoring Progression to Ovarian Cancer Using Plasma Label-free Proteomics

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