Prognostic Value of Novel Liquid Biomarkers in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: A Prospective Observational Study

Benoist, Guillemette E.; Oort, Inge M. van; Boerrigter, Emmy; Verhaegh, Gerald W.; Hooij, Onno van; Groen, Levi; Smit, Frank; Mol, Pieter de; Hamberg, Paul; Dezentjé, Vincent O.; Mehra, Niven; Gerritsen, Winald R.; Somford, Diederik M.; Erp, Nielka P.H. Van; Schalken, Jack A.

doi:10.1093/clinchem/hvaa095

Cited by 30 publications

(33 citation statements)

References 44 publications

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“…Nevertheless, several recent studies support their relevance by different methods. Benoist et al 83 identified hsa-miR-3687 as a novel prognostic marker for response in patients with castration-resistant prostate cancer treated with enzalutamide. This miRNA may also confer aggressiveness of oesophagus cancer through its target gene PGRMC2 84 .…”

Section: Discussionmentioning

confidence: 99%

Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer

Kolečková

Ehrmann

Bouchal

et al. 2021

Sci Rep

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Triple negative breast cancers (TNBC) are a morphologically and genetically heterogeneous group of breast cancers with uncertain prediction of biological behavior and response to therapy. Epithelial to mesenchymal transition (EMT) is a dynamic process characterized by loss of typical epithelial phenotype and acquisition of mesenchymal characteristics. Aberrant activation of EMT can aggravate the prognosis of patients with cancer, however, the mechanisms of EMT and role of microRNAs (miRNAs) in EMT activation is still unclear. The aim of our study was to analyze miRNA expression within areas of TNBCs with cellular morphology that may be related to the EMT process and discuss possible associations. Out of all 3953 re-examined breast cancers, 460 breast cancers were diagnosed as TNBC (11.64%). With regard to complete tumor morphology preservation, the tissue samples obtained from core—cut biopsies and influenced by previous neoadjuvant therapy were excluded. We assembled a set of selected 25 cases to determine miRNA expression levels in relation to present focal spindle cell and apocrine cell morphology within individual TNBCs. We used descriptive (histological typing and morphology), morphometric, molecular (microdissection of tumor and non-tumor morphologies, RNA isolation and purification, microchip analysis) and bioinformatic analysis (including pathway analysis). The results were verified by quantitative real-time PCR (RT-qPCR) on an extended set of 70 TNBCs. The majority of TNBCs were represented by high—grade invasive carcinomas of no special type (NST) with medullary features characterized by well-circumscribed tumors with central necrosis or fibrosis and frequent tendency to spindle-cell and/or apocrine cell transformation. Apocrine and spindle cell transformation showed a specific miRNA expression profile in comparison to other tumor parts, in situ carcinoma or non-tumor structures, particularly down-regulated expression of hsa-miRNA-143-3p and hsa-miRNA-205-5p and up-regulated expression of hsa-miR-22-3p, hsa-miRNA-185-5p, and hsa-miR-4443. Apocrine cell tumor morphology further revealed decreased expression of hsa-miR-145-5p and increased expression of additional 14 miRNAs (e.g. hsa-miR-182-5p, hsa-miR-3135b and hsa-miR-4417). Pathway analysis for target genes of these miRNAs revealed several shared biological processes (i.e. Wnt signaling, ErbB signaling, MAPK signaling, endocytosis and axon guidance), which may in part contribute to the EMT and tumor progression. We provide the first miRNA expression profiling of specific tissue morphologies in TNBC. Our results demonstrate a specific miRNA expression profile of apocrine and spindle cell morphology which can exhibit a certain similarity with the EMT process and may also be relevant for prognosis and therapy resistance of TNBC.

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Section: Discussionmentioning

confidence: 99%

Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer

Kolečková

Ehrmann

Bouchal

et al. 2021

Sci Rep

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“…In an analysis of plasma/serum samples from 97 mCRPC patients, Lin et al (20) found that low levels of miR-21 correlated with a shorter OS following treatment with docetaxel. A recent analysis by Benoist et al of miRNAs in whole blood samples did not reveal significant differences in the levels of miR-21 or miR-141 in mCRPC patients treated with enzalutamide compared to healthy volunteers (21). However, miRNAs detected in whole blood samples will be predominantly represented by those contained in erythrocytes, platelets and leukocytes, which likely mask the contribution of circulating cell-free miRNAs.…”

Section: Discussionmentioning

confidence: 93%

Prognostic Stratification of Metastatic Prostate Cancer Patients Treated With Abiraterone and Enzalutamide Through an Integrated Analysis of Circulating Free microRNAs and Clinical Parameters

et al. 2021

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Androgen Receptor-Targeted Agents (ARTA) have dramatically changed the therapeutic landscape of metastatic Castration-Resistant Prostate Cancer (mCRPC), but 20–40% of these patients progress early after start of ARTA treatment. The present study investigated the potential utility of plasma cell-free microRNAs (cfmiRNAs) as prognostic markers by analyzing a prospective cohort of 31 mCRCP patients treated with abiraterone (N = 10) or enzalutamide (N = 21). Additional potential prognostic factors were extracted from clinical records and outcome was evaluated as overall survival (OS) and progression-free survival (PFS). cfmiRNAs were measured in plasma samples using quantitative real-time RT-PCR. Linear correlation among clinical factors and cfmiRNAs was assessed using the Spearman's rank correlation coefficient. The association with survival was studied using univariate and multivariate Cox proportional hazards models. Continuous variables were dichotomized with the cut points corresponding to the most significant relation with the outcome. Univariate analysis indicated that plasma levels of miR-21-5p, miR-141-3p and miR-223-3p, time to development of castration-resistance (tCRPC), and blood hemoglobin (Hb) levels strongly correlated with both PFS and OS. Multivariate analysis revealed that low plasma levels of miR-21, shorter tCRPC, and lower Hb values were independent factors predicting reduced PFS and OS. These findings suggest that the integrated analysis of cfmiRNAs, tCRPC, and Hb may provide a promising, non-invasive tool for the prognostic stratification of mCRPC patients treated with ARTA.

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“…Among these lncRNAs of the signature, some studies have shown that AC099850.3 is also used as an autophagy-related lncRNA signature model in hepatocellular carcinoma as well as oral and oropharyngeal squamous cell carcinoma [46,47]. Benoist GE et al revealed that patients with NAALADL2-AS2 high-expression showed a longer time to progression [48].…”

Section: Discussionmentioning

confidence: 99%

Identification of a nine ferroptosis-related lncRNA prognostic signature for lung adenocarcinoma

Tong¹,

Zhang

Yang

et al. 2021

Preprint

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Background: Recently, mounting of studies has shown that lncRNA affects tumor progression through the regulation of ferroptosis. The current study aims to construct a robust ferroptosis-related lncRNAs signature to increase the predicted value of lung adenocarcinoma (LUAD) by bioinformatics analysis. Methods: The transcriptome data were abstracted from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened by comparing 535 LAUD tissues with 59 adjacent non-LAUD tissues. Univariate Cox regression, lasso regression, multivariate Cox regression were conducted to design a ferroptosis-related lncRNA signature. This signature’s prognosis was verified by the log-rank test of Kaplan-Meier curve and the area under curve (AUC) of receiver operating characteristic (ROC) in train set, test set, and entire set. Furthermore, univariate and multivariate Cox regression were used to analyze its independent prognostic ability. The relationship of the ferroptosis-linked lncRNAs' expression and clinical variables was demonstrated by Wilcoxon rank-sum test and Kruskal-Wallis test. Gene set enrichment analysis (GSEA) was performed to signaling pathways it may involve.Results: 1224 differentially expressed lncRNAs were identified, of which 195 are ferroptosis-related lncRNAs. A nine ferroptosis-related lncRNAs (AC099850.3, NAALADL2-AS2, AL844908.1, AL365181.2, SMIM25, FAM83A-AS1, LINC01116, AL049836.1, C20orf197) prognostic signature was constructed. This model's prognosis in the high-risk group is obviously worse than that of the low-risk group in train set, test set, and entire set. The AUC of ROC predicting the three years survival in the train set, test set, and entire set was 0.754, 0.716, and 0.738, respectively. Moreover, the designed molecular signature was found to be an independent prognostic variable. The expression of these lncRNAs and the lncRNA signature are related to clinical stage, T stage, Lymph-node status, distant metastasis. Finally, GSEA analysis results show that the signature is involved in eight tumor-related and metabolism-related signaling pathwaysConclusion: The current study constructed, validated, and evaluated a nine ferroptosis-related lncRNA signature which can independently be used to predict the prognosis of LAUD patients, and may become a new therapeutic target.

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Prognostic Value of Novel Liquid Biomarkers in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: A Prospective Observational Study

Cited by 30 publications

References 44 publications

Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer

Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer

Prognostic Stratification of Metastatic Prostate Cancer Patients Treated With Abiraterone and Enzalutamide Through an Integrated Analysis of Circulating Free microRNAs and Clinical Parameters

Identification of a nine ferroptosis-related lncRNA prognostic signature for lung adenocarcinoma

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