Analysis of the ORFK1 hypervariable regions reveal distinct HHV-8 clustering in Kaposi’s sarcoma and non-Kaposi’s cases

Cordiali‐Fei, Paola; Trento, Elisabetta; Giovanetti, Marta; Presti, Alessandra Lo; Latini, Alessandra; D’Agosto, Giovanna; Bordignon, Valentina; Cella, Eleonora; Farchi, Francesca; Ferraro, C.; Parola, Ilaria Lesnoni La; Cota, Carlo; Sperduti, Isabella; Vento, Antonella; Cristaudo, Antonio; Ciccozzi, Massimo; Ensoli, Fabrizio

doi:10.1186/s13046-014-0119-0

Cited by 115 publications

(103 citation statements)

References 65 publications

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“…Investigation of biomarkers potentially useful for KS prognosis based on different loci of genome [9,10,12,14,15,18] or whole-genome data [16] has advanced parallel to the molecular characterization of a large number of HHV-8 strains infecting patients from different clinical and epidemiological forms of KS. [9,10,12,14,15] For example, several short targets of HHV-8 from AIDS-KS lesions were selected to identify distinctive molecular pattern, but with restricted coverage of the repertoire of HHV-8 genotypes.…”

Section: Introductionmentioning

confidence: 99%

“…[9,10,12,14,15] For example, several short targets of HHV-8 from AIDS-KS lesions were selected to identify distinctive molecular pattern, but with restricted coverage of the repertoire of HHV-8 genotypes. [17–19,12,20–23] Nowadays, sequence analysis of highly variable ORF K1 regions (i.e., VR1 and VR2) has allowed the identification of 7 major subtypes or genotypes of HHV-8 (A, B, C, D, E, F, and Z), all exhibiting clear ethnic and geographic clustering.…”

Section: Introductionmentioning

confidence: 99%

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Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma

Tozetto‐Mendoza¹,

Ibrahim²,

Tateno

et al. 2016

Medicine

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AIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by polymerase chain reaction (PCR) techniques for detection of the fragments of ORF K1 of HHV-8, which were then genotyped and analyzed regarding the genetic variability. Our study described 106 positive cases for HHV-8 in the saliva from 751 AIDS patients without previous KS. In addition, we performed a phylogenetic analysis of HHV-8 in 34 of the 106 AIDS patients without KS and in 33 of the 37 patients with active KS. The distribution of HHV-8 genotypes A, B, C, and F in AIDS individuals was indistinguishable by comparing non-KS and KS groups, as well as regarding ethnicity. Considering the KS group, genotype B was associated with better prognosis of KS tumor. Interestingly, we found a particular profile of diversity within clade C and 2 recombinant patterns of HHV-8 in the saliva of AIDS individuals without KS. We emphasize the need to achieve standard genotyping protocol for ORF K1 amplification, thus allowing for substantial detection of HHV-8 variants. Our findings can shed light on the role of HHV-8 variability in the pathogenesis of AIDS-KS.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma

Tozetto‐Mendoza¹,

Ibrahim²,

Tateno

et al. 2016

Medicine

View full text Add to dashboard Cite

show abstract

“…The clinical relevance of piRNAs was first apparent when they were reported to be associated with clinicopathological factors such as lymph node status [23], and TNM stage [24]. Nonetheless, our understanding of their contribution as prognostic markers is rudimentary and warrants further exploration.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, the differential expression of piRNAs and therefore their oncogenic or tumor suppressor roles have also been observed in various cancer types [19, 20], and a few studies have highlighted their association with clinicopathological factors [23]. An even smaller number of studies have reported the relevance of piRNAs as prognostic/diagnostic markers [24–26]; however, the study designs of the majority of these studies are limited to candidate piRNA molecules or are challenged with limited sample sizes.…”

Section: Introductionmentioning

confidence: 99%

Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer

et al. 2016

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Piwi-interacting RNAs (piRNAs), whose role in germline maintenance has been established, are now also being classified as post-transcriptional regulators of gene expression in somatic cells. PIWI proteins, central to piRNA biogenesis, have been identified as genetic and epigenetic regulators of gene expression. piRNAs/PIWIs have emerged as potential biomarkers for cancer but their relevance to breast cancer has not been comprehensively studied. piRNAs and mRNAs were profiled from normal and breast tumor tissues using next generation sequencing and Agilent platforms, respectively. Gene targets for differentially expressed piRNAs were identified from mRNA expression dataset. piRNAs and PIWI genes were independently assessed for their prognostic significance (outcomes: Overall Survival, OS and Recurrence Free Survival, RFS). We discovered eight piRNAs as novel independent prognostic markers and their association with OS was confirmed in an external dataset (The Cancer Genome Atlas). Further, PIWIL3 and PIWIL4 genes showed prognostic relevance. 306 gene targets exhibited reciprocal relationship with piRNA expression. Cancer cell pathways such as apoptosis and cell signaling were the key Gene Ontology terms associated with the regulated gene targets. Overall, we have captured the entire cascade of events in a dysregulated piRNA pathway and have identified novel markers for breast cancer prognostication.

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“…As lncRNAs do not code for proteins, lncRNA expression may be a better indicator of the tumor status, implying the potential and superiority as independent biomarkers for early diagnosis and prognosis prediction in cancers [29]. Currently, several expression-based lncRNA signature have been identified to predict patients' survival in some cancers, including glioblastoma multiforme [30], oesophageal squamous cell carcinoma [31], colorectal cancer [32], breast cancer [33–35], lung cancer [36] and multiple myeloma [37]. Recent studies have revealed that changes in lncRNA expression were associated with OvCa tumorigenesis and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer

et al. 2016

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There is growing evidence of dysregulated long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic efforts of searching for an expression-based lncRNA signature for prognosis prediction in ovarian cancer (OvCa) have not been made yet. Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of 544 OvCa patients from The Cancer Genome Atlas (TCGA), and identified an eight-lncRNA signature with ability to classify patients of the training cohort into high-risk group showing poor outcome and low-risk group showing significantly improved outcome, which was further validated in the validation cohort and entire TCGA cohort. Multivariate Cox regression analysis and stratified analysis demonstrated that the prognostic value of this signature was independent of other clinicopathological factors. Associating the outcome prediction with BRCA1 and/or BRCA2 mutation revealed a superior prognosis performance both in BRCA1/2-mutated and BRCA1/2 wild-type tumors. Finally, a significantly correlation was found between the lncRNA signature and the complete response rate of chemotherapy, suggesting that this eight-lncRNA signature may be a measure to predict chemotherapy response and identify platinum-resistant patients who might benefit from other more efficacious therapies. With further prospective validation, this eight-lncRNA signature may have important implications for outcome prediction and therapy decisions.

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Analysis of the ORFK1 hypervariable regions reveal distinct HHV-8 clustering in Kaposi’s sarcoma and non-Kaposi’s cases

Cited by 115 publications

References 65 publications

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma

Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer

Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer

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