mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients

Kontos, Christos K.; Adamopoulos, Panagiotis G.; Papageorgiou, Sotirios G.; Pappa, Vassiliki; Scorilas, Andreas

doi:10.1515/cclm-2015-0456

Cited by 10 publications

(5 citation statements)

References 49 publications

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“…Similar signatures consisting of miRNAs have been proposed in prostate cancer (59,60), laryngeal squamous cell carcinoma (61), and other human malignancies (62). Multiparametric panels of biomarkers could also integrate protein-coding transcripts produced by cancer-related genes such as the apoptosis-related genes BCL2L12 (63-67), BCL2 (68,69) and BAX (70,71), DDC (72)(73)(74)(75), transcription factors such as HIF1 (39), and/or other mRNAs with significant prognostic value in human malignancies (76)(77)(78)(79)(80)(81)(82)(83). Besides that, miRNAs can stably circulate in human body fluids (e.g., plasma, urine etc.…”

Section: Introductionmentioning

confidence: 77%

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Diamantopoulos¹,

Tsiakanikas²,

Scorilas³

2018

Ann. Transl. Med.

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105

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Non-coding RNAs (ncRNAs) constitute a heterogeneous group of RNA molecules in terms of biogenesis, biological function as well as length and structure. These biological molecules have gained attention recently as a potentially crucial layer of tumor cell progression or regulation. ncRNAs are expressed in a broad spectrum of tumors, and they play an important role not only in maintaining but also in promoting cancer development and progression. Recent discoveries have revealed that ncRNAs may act as key signal transduction mediators in tumor signaling pathways by interacting with RNA or proteins. These results reinforce the hypothesis, that ncRNAs constitute therapeutic targets, and point out their clinical potential as stratification markers. The major purpose of this review is to mention the emergence of the importance of ncRNAs, as molecules which are correlated with cancer, and to discuss their clinical implicit as prognostic diagnostic indicators, biomarkers, and therapeutic targets.

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Section: Introductionmentioning

confidence: 77%

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Diamantopoulos¹,

Tsiakanikas²,

Scorilas³

2018

Ann. Transl. Med.

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105

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“…To date, a lot of genes are known to express alternative splice variants, some of which may have significant clinical value (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). The family of KLKs constitutes such a prominent example (28,29), as particular splice variants of the KLK1-KLK15 genes have been highlighted as putative biomarkers in human malignancies (30)(31)(32)(33)(34)(35). Very recently, ASDT has been used to partially reveal novel transcripts of tissue kallikrein (KLK1) (36) and several other members of the kallikrein-related peptidase (KLK) family (36)(37)(38)(39), as well as splice variants of the BCL2L12 gene (40,41), a prominent member of the apoptosis-related BCL2 family (42,43) with important prognostic value both in regard with solid tumors (44)(45)(46) as well as hematological malignancies (47,48), similarly to the major members of the BCL2 family, namely BCL2 and BAX (49)(50)(51).…”

Section: Biological and Clinical Significance Of Splice Variantsmentioning

confidence: 99%

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Adamopoulos¹,

Theodoropoulou²,

Scorilas³

2018

Ann. Transl. Med.

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Next-generation sequencing (NGS) can provide researchers with high impact information regarding alternative splice variants or transcript identifications. However, the enormous amount of data acquired from NGS platforms make the analysis of alternative splicing events hard to accomplish. For this reason, we designed the "Alternative Splicing Detection Tool" (ASDT), an algorithm that is capable of identifying alternative splicing events, including novel ones from high-throughput NGS data. ASDT is available as a PERL script at http://aias.biol.uoa.gr/~mtheo and can be executed on any system with PERL installed. In addition to the detection of annotated and novel alternative splicing events from high-throughput NGS data, ASDT can also analyze the intronic regions of genes, thus enabling the detection of novel cryptic exons residing in annotated introns, extensions of previously annotated exons, or even intron retentions. Consequently, ASDT demonstrates many innovative and unique features that can efficiently contribute to alternative splicing analysis of NGS data.

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“…Moreover, multivariate Cox regression analysis unveiled the independent prognostic significance of this tRF for B-CLL, suggesting the potential integration of tRF-Leu AAG/TAG in a multifactorial model, along with the currently established prognosticators. In the same direction, our research group intends to assess the prognostic significance of this molecule in a larger cohort of B-CLL patients, along with other promising molecular biomarkers, including HIF1A, 45 BCL2L12, 46 KLK14, 47 and/or particular miRNAs. 16 In conclusion, the aim of this study was to investigate the potential value of a tRF belonging to the tRF-3 group, as a prognostic and/ or screening biomarker for B-CLL.…”

Section: Discussionmentioning

confidence: 99%

A 3′ tRNA‐derived fragment produced by tRNA^LeuAAG and tRNA^LeuTAG is associated with poor prognosis in B‐cell chronic lymphocytic leukemia, independently of classical prognostic factors

Katsaraki

Adamopoulos

Papageorgiou

et al. 2021

European J of Haematology

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Objective 3′ tRNA‐derived fragments (3′ tRFs) are important epigenetic regulators in normal and pathological conditions. In this study, we aimed to explore the potential value of a 3′ tRF as a prognostic and/or screening biomarker for B‐cell chronic lymphocytic leukemia (B‐CLL). Methods Publicly available next‐generation sequencing data from 20 B‐CLL cases were analyzed, followed by prediction of targets of the most abundantly and ubiquitously expressed 3′ tRFs, leading to selection of tRF‐LeuAAG/TAG. PBMCs were isolated from blood samples of 91 B‐CLL patients and 43 non‐leukemic donors, followed by total RNA extraction, in‐vitro polyadenylation, and first‐strand cDNA synthesis. Next, a real‐time quantitative PCR (qPCR) assay was developed for the accurate quantification of tRF‐LeuAAG/TAG and applied in all samples, prior to biostatistical analysis. Results High tRF‐LeuAAG/TAG levels are associated with inferior overall survival (OS) of B‐CLL patients. The unfavorable significance of tRF‐LeuAAG/TAG was independent of established prognostic factors in B‐CLL. Stratified Kaplan‐Meier OS analysis uncovered the unfavorable prognostic role of high tRF‐LeuAAG/TAG levels for patients in Binet A or Rai I stage, negative CD38 expression, mutated, or unmutated IGHV genomic locus. Conclusion Our approach revealed the independent prognostic value of a particular 3′ tRF, derived from tRNALeuAAG and tRNALeuTAG (tRF‐LeuAAG/TAG) in B‐CLL.

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mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients

Abstract: KLK14 mRNA expression merits further investigation as a potential prognostic biomarker of overall survival of patients with CLL.

Cited by 10 publications

References 49 publications

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

A 3′ tRNA‐derived fragment produced by tRNA^LeuAAG and tRNA^LeuTAG is associated with poor prognosis in B‐cell chronic lymphocytic leukemia, independently of classical prognostic factors

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mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients

Abstract: KLK14 mRNA expression merits further investigation as a potential prognostic biomarker of overall survival of patients with CLL.

Cited by 10 publications

References 49 publications

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

A 3′ tRNA‐derived fragment produced by tRNALeuAAG and tRNALeuTAG is associated with poor prognosis in B‐cell chronic lymphocytic leukemia, independently of classical prognostic factors

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A 3′ tRNA‐derived fragment produced by tRNA^LeuAAG and tRNA^LeuTAG is associated with poor prognosis in B‐cell chronic lymphocytic leukemia, independently of classical prognostic factors