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Clear Cell Renal Cell Carcinoma Biomarkers

Inactive Publication Date: 2020-11-05
SINGAPORE HEALTH SERVICES PTE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention refers to a molecular biomarker set for detecting clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer. The biomarker set consists of at least two proteins or nucleic acids, including ZNF395, SMPDL3A, SLC28A1, SLC6A3, VEGFA, EGLN3, or their variants. The invention also provides a detection system and a method for using the biomarker set to determine if a subject has or shows recurrence ofccRCC, or if they are responsive to treatment. The biomarker set can also be used to determine if a renal mass sample is benign or malignant. The invention also includes a kit for carrying out the detection method and a detection system using the biomarker set.

Problems solved by technology

Renal cell carcinoma (RCC) is one of the most deadly cancers due to frequent late diagnosis and poor treatment options.
Therefore, identification of this high-risk group of renal cell carcinoma patients remains a challenge.
However, based on known methods, it is difficult to determine whether a renal mass of less than 4 cm is a tumour, and / or whether the tumour is benign or malignant based on imaging studies alone.
Surgery or ablation would result in tissue change and scar formation, causing the detection of local recurrence to be challenging.
Lastly, there is also a lack of methods to assess the efficiency of systemic treatments in advanced clear cell renal cell carcinoma patients.

Method used

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Examples

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example 1

and Methods

Patient Information

[0082]Fresh-frozen normal-tumour tissues were obtained from nephrectomy cases under approvals from institutional research ethics review committees and patient consent. Normal tissues were harvested from sites distant from the tumour. Table 1 refers to detailed patient information of this study.

TABLE 1Patient informationAge at theFuhrmantime ofNuclearIDdiagnosisRaceSexHisto TypeGrade7457585980ChineseFemaleClear cell carcinomaGrade II1762195348ChineseMaleClear cell carcinomaGrade II5739866756ChineseMaleClear cell carcinomaGrade III7052883552ChineseMaleClear cell carcinomaGrade III7797208350ChineseMaleClear cell carcinomaGrade IV7541692349Un-MaleClear cell carcinomaGrade IIknown2043171365IndianMaleClear cell carcinomaGrade IVwith pappilaryfeatures4091143256ChineseFemaleClear cell carcinomaGrade II12364284Un-Un-Un-Clear cell carcinomaGrade IIIknownknownknown8604910251ChineseMaleClear cell carcinomaGrade II

Cell Lines

[0083]Commercial cell lines (786-O, A-498,...

example 2

atory Landscapes in Clear Cell Renal Cell Carcinoma Tumours are Aberrant

[0123]To explore whether clear cell renal cell carcinoma tumours display alterations in their cis-regulatory landscapes in vivo, histone chromatin immunoprecipitation sequencing (ChIP-seq) profiles (3 marks: H3K27ac, H3K4me3, and H3K4me1) were generated in 10 primary tumour / normal pairs, 5 patient-matched tumour-derived cell lines, 2 commercially available clear cell renal cell carcinoma lines (786-O and A-498), and 2 normal kidney cell lines (HK2 and PCS-400. Table 1 in example 1 shows patient clinical information. Of the original 87 samples, 79 samples passed pre-sequencing quality-control filters and were subjected to ChIP-seq processing and downstream analysis. In total, 2,363,904,778 uniquely mapped reads were generated. On average, 89% of H3K27ac peaks, 98% of H3K4me3 peaks, and 76% of H3K4me1 peaks obtained in our normal kidney tissues overlapped with peaks from adult kidney tissues in the Epigenomics Roa...

example 3

ecific Enhancers are Associated with Hallmarks of Clear Cell Renal Cell Carcinoma

[0127]To identify genes modulated by the tumour-specific regulatory elements, enhancers were assigned using three approaches. The first approach utilized predefined linear proximity rules involving a set of highly confident genes (GREAT algorithm). MSigDB pathway analysis using GREAT-assigned genes revealed that gained enhancers exhibit a highly significant renal cell carcinoma-specific signature compared with gained promoters (enhancer q-value=3.2×10−26; promoter q-value=1.5×10−1, binomial FDR; FIG. 2A). Although gained promoters were involved in general cancer processes (for example, cell cycle, transcription, and RNA metabolism) for a complete list of promoter pathways), gained enhancers were enriched in disease-specific features of clear cell renal cell carcinoma, including HIF1α network activity, proangiogenic pathways (platelet activation and PDGFRβ signaling), and SLC-mediated transmembrane trans...

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Abstract

Disclosed herein is a clear cell renal cell carcinoma (ccRCC) biomarker set. Also disclosed herein is a detection system using the biomarker set disclosed herein, methods of determining whether a subject has or shows recurrence of clear cell renal cell carcinoma, method of determining whether a renal mass sample is benign or malignant, method of detecting response of a subject to systemic treatment, and a kit for carrying out the same.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority of Singapore application No. 10201707218R, filed 5 Sep. 2017, the contents of it being hereby incorporated by reference in its entirety for all purposes.FIELD OF INVENTION[0002]The present invention relates to molecular biology in particular biomarkers. In particular, the present invention relates to biomarkers associated with clear cell renal cell carcinoma (ccRCC) and methods and uses thereof.BACKGROUND OF THE INVENTION[0003]Renal cell carcinoma (RCC) is one of the most deadly cancers due to frequent late diagnosis and poor treatment options. Success in curing the disease relies on early detection of RCC and complete resection of the malignant cells. Since the kidney lies deeply in the retroperitoneal space, renal cell carcinoma is primarily asymptomatic in the early phase and upon diagnosis the tumour is large and / or metastasized. The three most common subtypes of renal cell carcinoma are...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q2600/106G01N33/57438C12Q2600/158C12Q1/6886C12Q2600/112
Inventor YAO, XIAOSAITAN, PATRICKTEH, BIN TEANTAN, JINGSHAO, HUILINKOH, JOANNA
Owner SINGAPORE HEALTH SERVICES PTE
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