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Application of HIC1 (hypermethylated in cancer 1) to diagnosis, treatment, prognosis and recurrence prediction of tumors

A tumor and prognosis technology, applied in the medical field, can solve the problems of HIC1 application and field gaps, and achieve the effect of improving invasion and metastasis, inhibiting invasion and metastasis, and improving survival rate

Inactive Publication Date: 2017-10-20
王建华
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the prior art, HIC1 has not been applied to tumor diagnosis or treatment, and the above-mentioned fields are still blank.

Method used

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  • Application of HIC1 (hypermethylated in cancer 1) to diagnosis, treatment, prognosis and recurrence prediction of tumors
  • Application of HIC1 (hypermethylated in cancer 1) to diagnosis, treatment, prognosis and recurrence prediction of tumors
  • Application of HIC1 (hypermethylated in cancer 1) to diagnosis, treatment, prognosis and recurrence prediction of tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1: Reduced expression of HIC1 in tumor cells and tissues

[0070] 1. Loss of HIC1 expression in triple-negative breast cancer cells (TNBC) and tissues

[0071] Such as figure 1 Shown is the expression status of HIC1 in several commonly used breast cancer cell lines. The results showed that the expression of HIC1 in the TNBC cell line MDA-231 was significantly lower than that in the Luminal cell lines MCF-7 and BT474, the HER2+ positive cell line SK-BR-3, and the benign cell line MCF-10A. However, compared with benign MCF-10A, the expression of HIC1 in breast cancer cell lines did not show a downward trend.

[0072] Next, high-density tissue chips were used to detect the expression of HIC1 in breast cancer patient specimens by immunohistochemical staining. Such as figure 2 As shown, the staining results showed that the expression of HIC1 in TNBC was almost lost compared with benign tissue, Luminal type, HER-2+. As shown in Table 1, subsequent statistical an...

Embodiment 2

[0104] Example 2: HIC1 deletion is positively correlated with patient survival and prognosis

[0105] 1. Loss of HIC1 gene expression is positively correlated with survival and prognosis of patients with triple-negative breast cancer

[0106] In order to further explore the correlation between HIC1 and the prognosis and survival rate of clinical patients, the published breast cancer clinical gene chip database was analyzed. As of November 2013, the database has included chip results of 1027 cases of breast cancer patients, of which 185 cases are effective Basal-type breast cancer (in the general sense, TNBC is equivalent to Basal-like type). The analysis results shown in Figure 11B suggest that the low expression of HIC1 is significantly correlated with the poor prognosis of basal-like patients (p=0.028), but in the entire breast cancer database and other molecular subtypes of breast cancer, as shown in Figure 11B, There was no statistical significance between the expression ...

Embodiment 3

[0112] Example 3: Construction of a stable cell line highly expressing HIC1 and construction of sh HIC1 cell line.

[0113] 1. Construction of a stable cell line with high expression of HIC1

[0114] 1. Construction of HIC1 overexpression plasmid packaging lentivirus

[0115] (1) Clone CDS: clone the CDS sequence from the non-viral expression plasmid (PC3.1 backbone) containing HIC1;

[0116] (2) Digest the CDS sequence and carrier (pHR-SIN-CSIGW), and recover the digested product from the gel;

[0117] (3) Ligate the digested CDS sequence with the lentiviral vector in proportion, transform the ligated product, pick clones, extract plasmids, and sequence to identify positive clones;

[0118] (4) Plasmid extraction: the constructed target plasmid is subjected to ultra-pure endotoxin-free extraction to reach the level of cell transfection (concentration above 1 μg, purity OD value greater than 1.8);

[0119] (5) Lentivirus packaging: The lentivirus packaging plasmids (PMD2.G,...

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Abstract

The invention discloses an application of HIC1 (hypermethylated in cancer 1) to diagnosis, treatment, prognosis and recurrence prediction of tumors. The invention discovers that the copy number and the expression level of HIC1 in various tumors are closely related with invasion, metastasis, recurrence and prognosis of the tumors. Research finds that decreased expression of HIC1 caused by hypermethylation of HIC1 can promote invasion and metastasis of the tumors, and the expression decrease degree of HIC1 is in negative correlation with prognosis of patients. By restoring expression of HIC1, invasion and metastasis abilities of breast cancer, prostate cancer and lung cancer can be effectively weakened, and the survival rate of the patients is increased, so that HIC1 can serve as a marker for diagnosis, treatment, prognosis and recurrence prediction of the tumors, and a kit can be prepared from HIC1. Drugs capable of promoting HIC1 expression have great clinical application value in preparation of tumor treatment pharmaceutical composition, and novel drugs and methods are provided for effective treatment of the tumors.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of HIC1 in tumor diagnosis, treatment, prognosis and recurrence prediction. Background technique [0002] Cancer hypermethylation gene 1 (HIC1) is a new tumor suppressor gene, located in the short arm of human chromosome 17 region 13, at the distal end of p53 site. In a variety of human tumor tissues, HIC1 is often silenced by deletion or promoter hypermethylation modification, including breast cancer, prostate cancer, lung cancer and colon cancer. This promoter methylation modification is not constant, but there is a certain correlation with the malignancy of the tumor and the low survival rate. When tumor cells were treated with the demethylating agent 5-AZA, the expression of HIC1 could be restored and the invasiveness of tumor cells could be inhibited. Further studies found that heterozygous deletion of HIC1 caused spontaneous tumors to be associated with hypermethyl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68A61K45/00A61P35/00
CPCA61K45/00C12Q1/6886C12Q2600/118C12Q2600/158
Inventor 王建华郝旻罡成广存郑江花王秀敏王莹莹孟祥军
Owner 王建华
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