Clear cell renal cell carcinoma biomarkers

A biomarker, clear cell technology, applied in the determination/examination of microorganisms, biochemical equipment and methods, instruments, etc., which can resolve tissue changes, lack of methods to assess the efficiency of systemic treatment in patients with advanced clear cell renal cell carcinoma, etc. question

Pending Publication Date: 2020-09-04
AGENCY FOR SCI TECH & RES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Surgery or ablation can cause tissue changes and scarring, making detection of local recurrence challenging
Finally, methods to assess the efficacy of systemic therapy in patients with advanced clear cell renal cell carcinoma are lacking
In light of the above, there is an unmet need for methods to identify clear cell renal cell carcinoma, to distinguish benign from malignant lesions, to detect recurrence after local therapy, and to evaluate systemic therapy

Method used

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  • Clear cell renal cell carcinoma biomarkers
  • Clear cell renal cell carcinoma biomarkers
  • Clear cell renal cell carcinoma biomarkers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] Example 1 - Materials and methods

[0089] patient information

[0090] Fresh-frozen normal tumor tissue was obtained from nephrectomy cases with institutional research ethics review board approval and patient consent. Normal tissue is collected from a site away from the tumor. Table 1 relates to detailed patient information for this study.

[0091] ID age at diagnosis Race gender Tissue type Fuhrman nuclear grade 74575859 80 China female clear cell carcinoma Class II 17621953 48 China male clear cell carcinoma Class II 57398667 56 China male clear cell carcinoma Class III 70528835 52 China male clear cell carcinoma Class III 77972083 50 China male clear cell carcinoma Class IV 75416923 49 unknown male clear cell carcinoma Class II 20431713 65 India male Clear cell carcinoma with papillary features Class IV 40911432 56 China female clear cell carcin...

Embodiment 2

[0215] Example 2 - Abnormal cis-regulatory patterns in clear cell renal cell carcinoma tumors

[0216] To explore whether clear cell renal cell carcinoma tumors exhibit changes in their cis-regulatory patterns in vivo, 10 primary tumor / normal pairs, 5 patient-matched tumor-derived cell lines, 2 commercially available Histone chromatin immunoprecipitation sequencing (ChIP-seq) profiles (3 markers) were generated in clear cell renal cell carcinoma lines (786-O and A-498) and 2 normal renal cell lines (HK2 and : H3K27ac, H3K4me3 and H3K4me1). Table 1 in Example 1 shows the clinical information of the patients. Of the original 87 samples, 79 samples passed the pre-sequencing quality control filter and were subjected to ChIP-seq processing and downstream analysis. A total of 2,363,904,778 uniquely mapped reads were generated. On average 89% of H3K27ac peaks, 98% of H3K4me3 peaks and 76% of H3K4mel peaks obtained in our normal kidney tissue overlapped with peaks from adult kidney...

Embodiment 3

[0222] Example 3 - Tumor-specific enhancers are associated with hallmarks of clear cell renal cell carcinoma

[0223] To identify genes regulated by tumor-specific regulatory elements, three methods were used to assign enhancers. The first approach utilizes a predefined linear proximity rule (GREAT algorithm) involving a set of high-confidence genes. MSigDB pathway analysis using GREAT-assigned genes revealed that the gain-in enhancer exhibited a highly significant renal cell carcinoma-specific signature compared to the gain-in promoter (enhancer q-value = 3.2 x 10 -26 ; promoter q value = 1.5 x 10 -1 , binomial FDR; figure 2 A). While the gain promoters are involved in general cancer processes (e.g. cell cycle, transcription, and RNA metabolism against a complete list of promoter pathways), the gain enhancers are enriched for disease-specific features of clear cell renal cell carcinoma, including targeting Complete list of enhancer pathways for HIF1α network activity, pr...

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Abstract

Disclosed herein is a clear cell renal cell carcinoma (ccRCC) biomarker comprising at least 2 biomarkers selected from the group consisting of ZNF395, SMPDL3A, SLC28A1, SLC6A3, VEGFA, EGLN3, wherein at least one of the two biomarkers is SMPDL3A or SLC28A1. Also enclosed 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, methods 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

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority from Singapore Application No. 10201707218R filed 5 September 2017, the contents of which are hereby incorporated by reference in their entirety for all purposes. [0003] field of invention [0004] The present invention relates to molecular biology, particularly biomarkers. In particular, the present invention relates to biomarkers associated with clear cell renal cell carcinoma (ccRCC) and methods and uses thereof. [0005] Background of the invention [0006] Renal cell carcinoma (RCC) is one of the deadliest cancers due to frequent diagnosis at an advanced stage and poor treatment options. Successful cure of the disease depends on early detection of RCC and complete excision of malignant cells. Because the kidney is located deep in the retroperitoneal space, renal cell carcinoma is largely asymptomatic in its early stages and, once diagnosed, the tumor is large and / o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574
CPCC12Q1/6886C12Q2600/158G01N33/57438C12Q2600/106C12Q2600/112
Inventor 姚晓赛陈文炜B·T·郑谭静邵慧琳J·许
Owner AGENCY FOR SCI TECH & RES
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