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Hypoxia-related gene marker combination for hepatocellular carcinoma and application thereof

A hepatocellular carcinoma and gene marker technology, applied in the field of biomedicine, can solve the problems of limited coverage and depth

Pending Publication Date: 2021-06-29
SHENZHEN PEOPLES HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the markers used in these studies are not specific to HCC, and because it is a pan-cancer research, the coverage and depth of the research content in the field of HCC is limited

Method used

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  • Hypoxia-related gene marker combination for hepatocellular carcinoma and application thereof
  • Hypoxia-related gene marker combination for hepatocellular carcinoma and application thereof
  • Hypoxia-related gene marker combination for hepatocellular carcinoma and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] This example provides a combination of hypoxia-related gene markers and a screening method for hepatocellular carcinoma.

[0075] (1) Firstly, through microarray analysis, the differentially expressed genes in HUH7, SNU-182 and HLF cells after hypoxia treatment for 24 hours were obtained (log FC>0.58 or log FC<-0.58, and P<0.05, FC: fold change; After taking the overlap (overlap), 748 differentially expressed genes co-existing among the three cell lines were obtained, including 321 up-regulated genes and 427 down-regulated genes.

[0076] In order to further understand the possible biological roles of these differentially expressed genes after hypoxia treatment, the biological process (biological process) and pathway enrichment analysis were carried out on these differentially expressed genes in this example. There was enrichment in the reaction, and pathway enrichment analysis indicated that the differentially expressed genes were enriched in the HIF-1 signaling pathwa...

Embodiment 2

[0082] In this example, the accuracy and stability of the hypoxia-related gene marker combination in evaluating the hypoxic state of HCC cells were verified.

[0083] (1) Accuracy:

[0084] In order to assess whether the combination of markers composed of these 21 genes can be used to estimate the hypoxic state of HCC cells, in this example, a hypoxia score (hypoxia score) was performed using gene set variation analysis (GSVA) calculation.

[0085] As shown in Figure 1(b), compared with the control group, HUH7, SNU-182 and HLF cells after hypoxia treatment had significantly higher hypoxia scores.

[0086] Similar results were verified in the GSE18494, GSE55214 and GSE57613 datasets, as shown in Figure 1(c), P<0.05. Therefore, the hypoxia score calculated based on the combination of hypoxia-related gene markers of these 21 genes can reflect the hypoxia of HCC cells.

[0087] (2) Stability:

[0088] In order to further prove the stability of the marker combination in assessi...

Embodiment 3

[0096] In this example, a marker combination composed of 21 genes was used for typing and prognostic analysis of HCC (TCGA-LIHC and GSE14520 data sets).

[0097] (1) Using unsupervised hierarchical cluster analysis, the patients (n=374) in the TCGA-LIHC dataset were typed based on marker combinations composed of 21 genes, as shown in Figure 2(a) , all patients can be divided into two subtypes using 21-gene signature:

[0098] The overall survival rate of patients with LIHC-B type was significantly lower than that of patients with LIHC-A type (Figure 2(b), HR=2.15, Log-rank P<0.01), and the disease-free survival rate was also lower than Low (Fig. 2(c), HR=2.17, Log-rank P<0.01).

[0099] LIHC-A type (n = 315) and LIHC-B type (n = 59), there were significant differences in TNM stage and AFP level between LIHC-A type and LIHC-B type patients. Among them, the prognosis of patients with LIHC-B type was poor: the proportion of patients with stage TNMⅢ-Ⅳ in LIHC-B type was higher (...

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Abstract

The invention provides a hypoxia-related gene marker combination for hepatocellular carcinoma and application thereof. A hypoxia score obtained by using the hypoxia-related gene marker combination can better reflect the hypoxia exposure condition of hepatocellular carcinoma tissues, and the hepatocellular carcinoma is subjected to typing and prognosis analysis. Meanwhile, the hypoxia-related gene marker combination is used for comprehensively exploring the change of hypoxia-related molecular markers in the hepatocellular carcinoma from multiple aspects of genomics, epigenomics, transcriptomics, proteomics and the like, a more complete hepatocellular carcinoma hypoxia-related molecular landscape is described, meanwhile, the immune microenvironment change of liver cancer is analyzed, and more valuable information is provided for diagnosis and treatment of the hepatocellular carcinoma.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to tumor prognosis markers, in particular to a combination of hypoxia-related gene markers for hepatocellular carcinoma and its application. Background technique [0002] Hepatocellular carcinoma (HCC) is the main histological subtype of liver cancer, accounting for 85-95% of primary liver cancer. The onset of HCC is insidious, and the clinical manifestations are highly heterogeneous. Most patients are already in the middle and late stage when they are diagnosed, thus losing the opportunity for surgery. The mortality rate of the middle and late stage patients is as high as 80%, the median survival time is less than 1 year, and the 5-year survival rate is less than 20%. Although the development of HCC targeted therapy drugs and immunotherapy in recent years has brought new hope to the treatment of patients with advanced HCC, it is undeniable that these treatments still have limitati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G16B20/20G16B25/00
CPCC12Q1/6886G16B20/20G16B25/00C12Q2600/118C12Q2600/112C12Q2600/158
Inventor 刘利平张强弩刘权严巧婷张育森孙哲鲍世韵
Owner SHENZHEN PEOPLES HOSPITAL
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