Multi-Marker Immunofluorescent Staining and PD-L1 Detection on Circulating Tumour Cells from Ovarian Cancer Patients

Asante, Du-Bois; Morici, Michael; Mohan, Ganendra Raj; Acheampong, Emmanuel; Spencer, Isaac; Lin, Weitao; Miert, Paula van; Gibson, Samantha; Beasley, Aaron B.; Ziman, Mel; Calapre, Leslie; Meniawy, Tarek; Gray, Elin S.

doi:10.3390/cancers13246225

Cited by 10 publications

(20 citation statements)

References 65 publications

(85 reference statements)

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“…Reinforcing trends were seen for the association of PD-L1 activity with pEMT signature one ( Figure 1 H). Thus, this pan-cancer meta-analysis highlights that the prominent mode of association in these pairwise comparisons is that PD-L1 activity correlates positively with a partial mesenchymal nature, reminiscent of recent experimental reports [ 18 , 22 , 45 ].…”

Section: Resultssupporting

confidence: 65%

PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas

Muralidharan

Sehgal

et al. 2022

Current Oncology

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Immune evasion and metabolic reprogramming are hallmarks of cancer progression often associated with a poor prognosis and frequently present significant challenges for cancer therapies. Recent studies have highlighted the dynamic interaction between immunosuppression and the dysregulation of energy metabolism in modulating the tumor microenvironment to promote cancer aggressiveness. However, a pan-cancer association among these two hallmarks, and a potent common driver for them—epithelial-mesenchymal transition (EMT)—remains to be done. This meta-analysis across 184 publicly available transcriptomic datasets as well as The Cancer Genome Atlas (TCGA) data reveals that an enhanced PD-L1 activity signature along with other immune checkpoint markers correlate positively with a partial EMT and an elevated glycolysis signature but a reduced OXPHOS signature in many carcinomas. These trends were also recapitulated in single-cell, RNA-seq, time-course EMT induction data across cell lines. Furthermore, across multiple cancer types, concurrent enrichment of glycolysis and PD-L1 results in worse outcomes in terms of overall survival as compared to enrichment for only PD-L1 activity or expression. These results highlight potential functional synergy among these interconnected axes of cellular plasticity in enabling metastasis and multi-drug resistance in cancer.

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Section: Resultssupporting

confidence: 65%

PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas

Muralidharan

Sehgal

et al. 2022

Current Oncology

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show abstract

“…Reinforcing trends were seen for association of PD-L1 activity with pEMT signature one ( Fig 1H ). Thus, this pan-cancer meta-analysis highlights that the prominent mode of association in these pairwise comparisons is that PD-L1 activity correlates positively with a partial mesenchymal nature, reminiscent of recent experimental reports [19,23,47].…”

Section: Resultssupporting

confidence: 65%

PD-L1 activity is associated with partial EMT and metabolic reprogramming in carcinomas

Muralidharan

Sehgal

et al. 2022

Preprint

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Immune evasion and metabolic reprogramming are hallmarks of cancer progression often associated with a poor prognosis and frequently present significant challenge for cancer therapies. Recent studies have emphasized on the dynamic interaction between immunosuppression and the dysregulation of energy metabolism in modulating the tumor microenvironment to promote cancer aggressiveness. However, a pan-cancer association among these two hallmarks, and a potent common driver for them – Epithelial-Mesenchymal Transition (EMT) – remains to be done. Here, our meta-analysis across 184 publicly available transcriptomic datasets as well as The Cancer Genome Atlas (TCGA) data reveals that an enhanced PD-L1 activity signature along with other immune checkpoint markers correlate positively with a partial EMT and elevated glycolysis signature but a reduced OXPHOS signature in many carcinomas. These trends were also recapitulated in single-cell RNA-seq time-course EMT induction data across cell lines. Furthermore, across multiple cancer types, concurrent enrichment of glycolysis and PD-L1 results in worse outcomes in terms of overall survival as compared to enrichment for only PD-L1 activity or expression. Our results highlight potential functional synergy among these interconnected axes of cellular plasticity in enabling metastasis and/or multi-drug resistance in cancer.

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“…But due to the expression of vimentin in circulating endothelial cells (CECs), CD31 was used as exclusion marker, similar to other studies 19 , 20 . We previously noted putative CTCs expressing CK/EpCAM as well as CD31 positive 18 , presenting as pseudoendothelial phenotype. Recently putative tumorigenic CECs with aneuploidy have been reported from OC 21 and lung cancer patients 22 .…”

Section: Introductionmentioning

confidence: 91%

“…In our recent study, we identified heterogeneous CTCs in ovarian cancer (OC) patients using a multi-marker immunostaining method for the detection of both epithelial and mesenchymal CTCs 18 . Mesenchymal CTCs were identified as vimentin positive cells.…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of heterogeneous subsets of circulating tumour cells from high grade serous ovarian carcinoma patients

Asante

Mohan

Acheampong

et al. 2023

Sci Rep

Self Cite

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Circulating tumour cells (CTCs) are heterogenous and contain genetic information from the tumour of origin. They bear specific intra- and extra-cellular protein markers aiding in their detection. However, since these markers may be shared with other rare cells in the blood, only genetic testing can confirm their malignancy. Herein, we analyse different CTC subsets using single cell whole genome DNA sequencing to validate their malignant origin. We randomly selected putative CTCs identified by immunostaining that were isolated from 4 patients with high grade serous ovarian cancer (HGSOC) and one with benign cystadenoma. We specifically targeted CTCs positive for epithelial (CK/EpCAMpos), mesenchymal (vimentinpos), and pseudoendothelial (CK/EpCAMpos plus CD31pos) markers. We isolated these cells and performed whole genome amplification (WGA) and low-pass whole-genome sequencing (LP-WGS) for analysis of copy number alterations (CNA). Of the CK/EpCAMpos cells analysed from the HGSOC patients, 2 of 3 cells showed diverse chromosomal CNAs. However, the 4 pseudoendothelial cells (CK/EpCAMpos plus CD31pos) observed in the HGSOC cases did not carry any CNA. Lastly, two of the clusters of vimentin positive cells sequenced from those found in the benign cystadenoma case had CNA. Despite the low number of cells analysed, our results underscore the importance of genetic analysis of putative CTCs to confirm their neoplastic origin. In particular, it highlights the presence of a population of CK/EpCAMpos cells that are not tumour cells in patients with HGSOC, which otherwise would be counted as CTCs.

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Multi-Marker Immunofluorescent Staining and PD-L1 Detection on Circulating Tumour Cells from Ovarian Cancer Patients

Cited by 10 publications

References 65 publications

PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas

PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas

PD-L1 activity is associated with partial EMT and metabolic reprogramming in carcinomas

Genetic analysis of heterogeneous subsets of circulating tumour cells from high grade serous ovarian carcinoma patients

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