RNA Biomarkers as a Response Measure for Survival in Patients with Metastatic Castration-Resistant Prostate Cancer

Boerrigter, Emmy; Benoist, Guillemette E.; Oort, Inge M. van; Verhaegh, Gerald W.; Haan, A.F.J. de; Hooij, Onno van; Groen, Levi; Smit, Frank; Oving, Irma M.; Mol, Pieter de; Smilde, Tineke J.; Somford, Diederik M.; Hamberg, Paul; Dezentjé, Vincent O.; Mehra, Niven; Erp, Nielka P. van; Schalken, Jack A.

doi:10.3390/cancers13246279

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…This hypothesis is supported by two of our recent publications. Here we found high plasma-AS2 levels in CRPC patients treated with ARSIs to be favorable for progression free survival and overall survival, while low AS2 levels were unfavorable [39,40]. These findings support the clinical utility of AS2 as a liquid biopsy-based biomarker in CRPC.…”

Section: Discussionsupporting

confidence: 79%

The Androgen Regulated lncRNA NAALADL2-AS2 Promotes Tumor Cell Survival in Prostate Cancer

Groen

Yurevych²,

Ramu³

et al. 2022

ncRNA

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Castration resistance is the leading cause of death in men with prostate cancer. Recent studies indicate long noncoding RNAs (lncRNAs) to be important drivers of therapy resistance. The aim of this study was to identify differentially expressed lncRNAs in castration-resistant prostate cancer (CRPC) and to functionally characterize them in vitro. Tumor-derived RNA-sequencing data were used to quantify and compare the expression of 11,469 lncRNAs in benign, primary prostate cancer, and CRPC samples. CRPC-associated lncRNAs were selected for semi-quantitative PCR validation on 68 surgical tumor specimens. In vitro functional studies were performed by antisense-oligonucleotide-mediated lncRNA knockdown in hormone-sensitive prostate cancer (HSPC) and CRPC cell line models. Subsequently, cell proliferation, apoptosis, cell cycle, transcriptome and pathway analyses were performed using the appropriate assays. Transcriptome analysis of a prostate cancer tumor specimens unveiled NAALADL2-AS2 as a novel CRPC-upregulated lncRNA. The expression of NAALADL2-AS2 was found to be particularly high in HSPC in vitro models and to increase under androgen deprived conditions. NAALADL2-AS2 knockdown decreased cell viability and increased caspase activity and apoptotic cells. Cellular fractionization and RNA fluorescent in situ hybridization identified NAALADL2-AS2 as a nuclear transcript. Transcriptome and pathway analyses revealed that NAALADL2-AS2 modulates the expression of genes involved with cell cycle control and glycogen metabolism. We hypothesize that the nuclear lncRNA, NAALADL2-AS2, functions as a pro-survival signal in prostate cancer cells under pressure of targeted hormone therapy.

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Section: Discussionsupporting

confidence: 79%

The Androgen Regulated lncRNA NAALADL2-AS2 Promotes Tumor Cell Survival in Prostate Cancer

Groen

Yurevych²,

Ramu³

et al. 2022

ncRNA

Self Cite

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“…At present, the established prognostic factors (ISUP, stage, and PSA) are insufficient to separate PC patients with high risk of cancer progression; moreover, molecular markers for metastatic propensity remain elusive [25]. RNA biomarkers are experiencing an increased interest in predicting progression-free survival and OS [26]. In the present article, we reinforced the role of PCA3, MRC2, and S100A4 in combination, and S100A4 on its own, as RNA biomarkers in PC aggressiveness stratification.…”

Section: Discussionmentioning

confidence: 64%

Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma

Álvarez-Cubero

Arance

Santiago

et al. 2022

IJMS

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The management and screening of prostate cancer (PC) is still the main problem in clinical practice. In this study, we investigated the role of aggressiveness genetic markers for PC stratification. We analyzed 201 plasma samples from PC patients and controls by digital PCR. For selection and validation, 26 formalin-fixed paraffin-embedded tissues, 12 fresh tissues, and 24 plasma samples were characterized by RNA-Seq, immunochemistry, immunofluorescence, Western blot, and extracellular-vesicles analyses. We identified three novel non-invasive biomarkers; all with an increased expression pattern in patients (PCA3: p = 0.002, S100A4: p ≤ 0.0001 and MRC2: p = 0.005). S100A4 presents the most informative AUC (area under the curve) (0.735). Combination of S100A4, MRC2, and PCA3 increases the discriminatory power between patients and controls and between different more and less aggressive stages (AUC = 0.761, p ≤ 0.0001). However, although a sensitivity of 97.47% in PCA3 and a specificity of 90.32% in S100A4 was reached, the detection signal level could be variable in some analyses owing to tumor heterogeneity. This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4, MRC2, and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness.

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“…Studies also revealed significant upregulation of LncRNA NAALADL2-AS2 in metastatic castration-resistant prostate cancer (mCRPC) and demonstrated NAALADL2-AS2 as a biomarkers of response measure for survival in patients with mCRPC [45]. Androgen regulated lncRNA NAALADL2-AS2 promoted the survival of prostate cancer cells, and transcriptome and pathway analyses revealed that NAALADL2-AS2 modulated the expression of genes involved with cell cycle control and glycogen metabolism [46].…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Long Non-Coding RNA Signatures for Tongue Squamous Cell Carcinoma

Messadi

2023

Current Oncology

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Background: Tongue squamous cell carcinoma (TSCC) represents one of the major subsets of head and neck cancer, which is characterized by unfavorable prognosis, frequent lymph node metastasis, and high mortality rate. The molecular events regulating tongue tumorigenesis remain elusive. In this study, we aimed to identify and evaluate immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in TSCC. Methods: The lncRNA expression data for TSCC were obtained from The Cancer Genome Atlas (TCGA) and the immune-related genes were downloaded from the Immunology Database and Analysis Portal (ImmPort). Pearson correlation analysis was performed to identify immune-related lncRNAs. The TCGA TSCC patient cohort was randomly divided into training and testing cohorts. In the training cohort, univariate and multivariate Cox regression analyses were used to determining key immune-related lncRNAs, which were then validated through Cox regression analysis, principal component analysis (PCA), and receiver operating characteristic (ROC) analysis in the testing cohort. Results: Six immune-related signature lncRNAs (MIR4713HG, AC104088.1, LINC00534, NAALADL2-AS2, AC083967.1, FNDC1-IT1) were found to have prognostic value in TSCC. Multivariate and univariate cox regression analyses showed that the risk score based on our six-lncRNA model, when compared to other clinicopathological factors (age, gender, stage, N, T), was an important indicator of survival rate. In addition, Kaplan–Meier survival analysis demonstrated significantly higher overall survival in the low-risk patient group than the high-risk patient group within both training and testing cohorts. The ROC analysis indicated that the AUCs for 5-year overall survival were 0.790, 0.691, and 0.721, respectively, for training, testing, and entire cohorts. Finally, PCA analysis demonstrated that the high-risk and low-risk patient groups presented significant deviation regarding their immune status. Conclusions: A prognostic model based on six immune-related signature lncRNAs was established. This six-lncRNA prognostic model has clinical significance and may be helpful in the development of personalized immunotherapy strategies.

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RNA Biomarkers as a Response Measure for Survival in Patients with Metastatic Castration-Resistant Prostate Cancer

Cited by 6 publications

References 45 publications

The Androgen Regulated lncRNA NAALADL2-AS2 Promotes Tumor Cell Survival in Prostate Cancer

The Androgen Regulated lncRNA NAALADL2-AS2 Promotes Tumor Cell Survival in Prostate Cancer

Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma

Immune-Related Long Non-Coding RNA Signatures for Tongue Squamous Cell Carcinoma

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