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Application of lncRNA combination to preparation of product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatment sensitivity

A technology of clear cell renal cell carcinoma and molecular targeted drugs, applied in the fields of molecular biology and medicine, can solve the problems of few lncRNA application research, and the value of tumor histological prognostic markers in renal clear cell carcinoma has not been reported in the literature.

Inactive Publication Date: 2018-07-13
NANJING GENERAL HOSPITAL NANJING MILLITARY COMMAND P L A
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  • Description
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  • Application Information

AI Technical Summary

Problems solved by technology

However, there is still very little research on the application of lncRNA in tumor histological markers
The value of the lncRNA prognostic risk score model as a histological prognostic marker for clear cell renal cell carcinoma has not been reported in the literature so far

Method used

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  • Application of lncRNA combination to preparation of product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatment sensitivity
  • Application of lncRNA combination to preparation of product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatment sensitivity
  • Application of lncRNA combination to preparation of product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatment sensitivity

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Embodiment 1: Establish RCClnc4 model

[0057] In previous studies, the inventors firstly used the transcriptome sequencing data of 52 pairs of clear cell renal cell carcinoma and normal kidney tissue (from America cohort from TCGA project (see literature Cancer Genome AtlasResearch Network.Comprehensive molecular characterization of clear cell renalcell carcinoma [ J].Nature,2013,499(7456):43)), 51 differentially expressed lncRNAs were screened out, and unsupervised cluster analysis showed that these lncRNAs could successfully distinguish cancer from normal tissues ( figure 1 ), except for one case of tumor tissue, so we took these 51 lncRNAs as candidate lncRNAs for predicting the prognosis risk of early clear cell renal cell carcinoma (TNM stage I-III). We randomly divided 444 patients with stage I-III clear cell renal cell carcinoma in TCGA into a training group (n=222) and an internal validation group (n=222), and there was no significant difference in clinicopatho...

Embodiment 2

[0059] Example 2: Preliminary verification of the RCClnc4 model

[0060] Subsequently, we selected the median of the RCClnc4 score (–0.323) in the training group as the cutoff value, and divided the patients with clear cell renal cell carcinoma in the training group into a low-risk group and a high-risk group. There was no significant difference in clinicopathological characteristics between the two groups ( p>0.05). Most of the patients who died in the training group were concentrated in the RCClnc4 high-risk group, and the Kaplan-Meier survival curve showed that the overall survival rate of patients with clear cell renal cell carcinoma in the RCClnc4 high-risk group in the training group was lower (p image 3 A). We further applied the above calculation formula and fixed cutoff value to the internal verification group from TCGA and the external verification group from Japan (EGAS00001000509, n=88), and the results showed that the RCClnc4 score can still divide the correspondi...

Embodiment 3

[0062] Embodiment 3: Further verification of RCClnc4 model

[0063] Next, we utilized three independent cohorts from China with long-term follow-up (independent validation group 1 from Changhai Hospital (n=1299), independent validation group 2 from Changzheng Hospital (n=346), independent validation group from Southwest Hospital Validation group 3 (n=224)) included 1869 patients with clear cell renal cell carcinoma to verify the efficacy of RCClnc4 score as a prognostic marker model for clear cell renal cell carcinoma.

[0064] The surgically resected cancer tissue specimens of the above clear cell renal cell carcinoma patients were collected; RNA samples were extracted using Qiagen’s RNeasyPlusMiniKit according to the kit instructions; the extracted RNA was quantitatively detected by NanoDrop2000 spectrometer for the concentration and quality of the extracted total RNA. The extracted RNA samples were frozen and stored in a deep freezer at -80°C. The RNA sample collected abov...

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Abstract

The invention discloses application of lncRNA combination to preparation of a product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatment sensitivity. The lncRNA or the lncRNA combination serving as a detection target point is applied to preparation of the product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatmentsensitivity, and the lncRNA or the lncRNA combination is selected from any one or more of SEQ ID NO.1 to SEQ ID NO.4. A new clinical method is provided for evaluating prognosis of patients sufferingfrom renal clear cell carcinoma, new reference advice is provided for auxiliary treatment after operation of the renal clear cell carcinoma, and important clinical significance and popularization andapplication prospect in the aspects of timely taking effective clinical measures, formulating an individualized diagnosis and treatment scheme and finally increasing the survival rate of the patientssuffering from the renal clear cell carcinoma are achieved.

Description

technical field [0001] The invention belongs to the fields of molecular biology and medicine, and specifically relates to the application of lncRNA combination in the preparation of products for predicting the prognosis of renal clear cell carcinoma and the sensitivity of molecular targeted drug treatment. Background technique [0002] Clear cell renal cell carcinoma is a highly heterogeneous tumor, and even patients with the same clinical stage have significantly different prognosis. After radical resection of early renal cell carcinoma, 20-30% of patients will eventually develop recurrence and metastasis; the 5-year survival rate of patients with advanced renal cell carcinoma is less than 30%, and the efficacy of the current first-line molecular targeted therapy is still unclear . If an accurate and effective prognostic assessment can be performed on patients with early clear cell renal cell carcinoma, it will be able to assist clinical practice selection, guide patients'...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/106C12Q2600/118C12Q2600/158C12Q2600/178
Inventor 曲乐陈程王林辉周文泉何昊玮
Owner NANJING GENERAL HOSPITAL NANJING MILLITARY COMMAND P L A
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