Clinical Relevance of Circulating Tumor Cells in Prostate Cancer Management

BackgroundCircular RNAs (circRNAs) are receiving increasing attention as novel biomarkers. Our goal was to investigate the diagnostic, clinicopathological, and prognostic utility of circRNAs in prostate cancer (PCa).MethodsRelevant literature was searched in PubMed, Web of Science, and EMBASE. Sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (NLR), positive likelihood ratio (PLR), and the area under the curve (AUC) were calculated to evaluate the diagnostic accuracy of circRNA expression. circRNAs’ clinical, pathological, and prognostic value was examined using pooled odds ratios (ORs) and hazard ratios (HRs).ResultsThis meta-analysis included 23 studies, with 5 for diagnosis, 16 for clinicopathological parameters, and 10 for prognosis. For diagnostic value, the pooled sensitivity, pooled specificity, PLR, NLR, DOR, and AUC were 0.82, 0.62, 2.17, 0.29, 7.37, and 0.81, respectively. Upregulation of carcinogenic circRNAs was associated with poor clinical parameters (Gleason score: OR = 0.222, 95% CI: 0.145–0.340; T classification: OR = 0.274, 95% CI: 0.175–0.430; lymph node metastasis: OR = 0.353, 95% CI: 0.175–0.716; tumor size: OR = 0.226, 95% CI: 0.099–0.518) and could predict poor survival outcomes (HR = 2.408, 95% CI: 1.559–3.720, p < 0.001). Conversely, downregulation of tumor-suppressor circRNAs was also associated with poor clinical parameters (Gleason score: OR = 1.689, 95% CI: 1.144–2.493; T classification: OR = 2.586, 95% CI: 1.779–3.762) and worse prognosis (HR = 1.739, 95% CI: 1.147–2.576, p = 0.006).ConclusionOur results showed that circRNAs might be useful biomarkers for the diagnosis and prognosis of PCa.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021284785.

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Section: Discussionmentioning

confidence: 99%

“…In recent years, the high incidence and mortality of PCa have caused worldwide concern ( 41 , 42 ). The diagnosis and prognosis of PCa are currently determined by tissue biopsy and PSA levels ( 42 ). However, tissue biopsy is invasive, and the predicted accuracy of PSA should be furthermore improved.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and diagnostic value of circRNA expression in prostate cancer: A systematic review and meta-analysis

Xie

Jiang²,

Zhao³

et al. 2022

Front. Oncol.

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“…Historically, the use of prostate specific antigen (PSA) and other blood based biomarkers have produced risk models with only moderate calibration and discrimination in the metastatic prostate cancer setting (Gafita et al 2021). As a result, exploring informative new biomarkers continues, with a recent focus around circulating tumor cells and serum testosterone (Cieslikowski et al 2021;Ryan et al 2019).…”

Section: Prostate Cancer Datamentioning

confidence: 99%

A Modified Net Reclassification Improvement Statistic

Heller¹

2022

Preprint

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The continuous net reclassification improvement (NRI) statistic is a popular model change measure that was developed to assess the incremental value of new factors in a risk prediction model. Two prominent statistical issues identified in the literature call the utility of this measure into question: (1) it is not a proper scoring function and ( 2) it has a high false positive rate when testing whether new factors contribute to the risk model. For binary response regression models, these subjects are interrogated and a modification of the continuous NRI, guided by the likelihood-based score residual, is proposed to address these issues. Within a nested model framework, the modified NRI may be viewed as a distance measure between two risk models. An application of the modified NRI is illustrated using prostate cancer data.

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“…It is currently recognized that the existence of CTCs is one of the main reasons for tumor recurrence or metastasis. Studies have demonstrated the prognostic value of CTCs testing in breast, lung, and prostate cancers [ 6 – 8 ]. Abnormally alternating (decreased or increased) chromosomes in cells are well-recognized markers of malignancy, studies have found that aneuploid karyotypes in CTCs can help explore cancer prognosis and treatment efficacy [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating tumor cells correlating with Ki-67 predicts the prognosis of bladder cancer patients

Liu

et al. 2022

Int Urol Nephrol

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Purpose To investigate the value of circulating tumor cells (CTCs) and Ki-67 in predicting the prognosis of bladder cancer. Here, we tested CTC counts and Ki-67 levels to assess patient prognosis. Methods 84 patients with bladder cancer who underwent surgery were included in this study. Peripheral blood CTCs were detected by SE-iFISH technology before and after surgery, and Ki-67 levels were analyzed by immunohistochemistry. The association between CTCs and Ki-67 and the combination of the two was analyzed to predict the prognosis of patients. Results 76 out of 84 patients (90.5%) were positive. ROC curve analysis showed that preoperative and postoperative CTC counts = 4 and 2 were the best thresholds for predicting patient recurrence or death. In multivariate analysis, high postoperative CTC count (≥ 2) (P < 0.001) and Ki-67 high expression (≥ 15%) (P < 0.001) were independent poor prognostic factors for PFS in bladder cancer patients. In addition, the study found that Ki-67 levels were positively correlated with high postoperative CTC counts, Bladder cancer patients with Ki-67 high expression and high postoperative CTC counts were associated with extremely poor progression-free survival. Conclusion Ki-67 high expression is associated with high postoperative CTC counts, both of which predict poor prognosis in bladder cancer patients.

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Clinical Relevance of Circulating Tumor Cells in Prostate Cancer Management

Cited by 29 publications

References 103 publications

Prognostic and diagnostic value of circRNA expression in prostate cancer: A systematic review and meta-analysis

Prognostic and diagnostic value of circRNA expression in prostate cancer: A systematic review and meta-analysis

A Modified Net Reclassification Improvement Statistic

Circulating tumor cells correlating with Ki-67 predicts the prognosis of bladder cancer patients

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