Methods for diagnosis and/or prognosis of gynecological cancer

A technology for survival prognosis and ovarian cancer, applied in the fields of biochemical equipment and methods, microbial determination/examination, etc., which can solve the problems of undisclosed, information contradiction of the role of MECOM locus, etc.

Inactive Publication Date: 2014-10-01
AGENCY FOR SCI TECH & RES
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  • Summary
  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

[0009] However, information on the role of the MECOM locus in ovarian cancer development has been conflicting
In a recent study, compared with different types of normal tissues, although EVI1 was significantly highly expressed in serous ovarian cancer tissues, fallopian tube fimbria and benign tumors, it was not tested in OVCAR8 cell culture (JazaeriAA, 2010). , did not reveal that EVI1 transcriptional expression had no effect on tumor cell proliferation, induction of apoptosis, or double-strand DNA breaks

Method used

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  • Methods for diagnosis and/or prognosis of gynecological cancer
  • Methods for diagnosis and/or prognosis of gynecological cancer
  • Methods for diagnosis and/or prognosis of gynecological cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0160] EVI1 gene expression is a distinguishing marker between normal and cancerous ovarian tissue

[0161] result in figure 1 , where expression of the EVI1 and MDS1 genes showing the MECOM locus is greatly increased in ovarian cancer cells relative to normal epithelial cells. In samples obtained from ovarian tissue using laser microdissection, the average expression of EVI1 and MDS1 genes was 3.6 and 1.4 times higher in cancerous tissues than in adjacent normal tissues ( figure 1 ). This difference in mean expression values ​​was more significant for EVI1 relative to MDS1 (p=0.021). MDS1 and EVI1 expression values ​​were associated with all samples (Pearson'sr=0.84, Kendall'sr=0.60).

Embodiment 2

[0162] Example 2 EVI1 expression is a sensitive and specific marker of primary EOC tumors among traditional diagnostic biomarkers

[0163]To assess the importance of EV1 in ovarian cancer, its expression was analyzed in three datasets and its importance as a diagnostic marker in the gene set was re-examined, its importance in ovarian cancer diagnosis and patient survival is widely accepted : KRAS, ERBB2, P53, MYC, MUC16 (CA-125) and WFDC2 (HE4). Results for WFDC2 and MUC16 are shown in figure 2 middle. It can be known from the results that MECOM expression is different in normal ovarian epithelial cells and cancerous ovarian epithelial cells. Combinations of expression values ​​of MECOM genes that differentiate EOC with false negative (FN)=1 and false positive (FP)=1 ( figure 2 (A)), which can be compared with figure 2 (C) Combination comparison of MUC16 (CA-125) and WWFDC2 (HE-4) markers. exist figure 2 (B) Perfect separation of the EV1 and MUC16 gene combinations w...

Embodiment 3

[0177] EVI1 expression is a sensitive marker of potential malignancy in EOC tumors

[0178] Regarding the potential malignancy of the tumor, the EVI1 gene ranked 5th (P=0.022) in terms of panel discrimination significance, surpassing the biomarkers MYC (P=0.03) and ERBB2 (P=0.74).

[0179] The specificity=21 / (21+4)=84% and the sensitivity=49 / (49+18)=73% of EVI1EVI1 at the expression cutoff level of 9.5, while the expression level of MUC16(CA-125) at the cutoff level of 9.7 Specificity=21 / (21+5)=81%, Sensitivity=49 / (49+11)=82%. exist Image 6 The comparison plot of the ROC curves shows that EVI1 as a clinical diagnostic biomarker proposed in the present invention is more effective than two proven clinical biomarkers MUC16 (CA-125) and WFDC2 (HE-4) at all ranges of cutoff values It is more conducive to classify patient groups. Image 6 The discrimination between primary EOC tumors and intra-ovarian breast cancer metastases is shown in the form of a two-dimensional discriminan...

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Abstract

The present invention relates to an in vitro method for diagnosing epithelial ovarian cancer, cervical cancer, endometriosis, clear cell renal carcinoma and / or predisposition to epithelial ovarian cancer in a subject, the method comprising determining in a sample of the subject gene expression level of at least one gene in the MDS 1 and EVI1 complex (MECOM) locus, and / or copy number of at least one gene in the MECOM locus, wherein the level against at least one expression cutoff value and / or copy number against at least one copy number cutoff value are indicative of the subject having epithelial ovarian cancer, cervical cancer, endometriosis, clear cell renal carcinoma and / or a predisposition to epithelial ovarian cancer cervical cancer, endometriosis, clear cell renal carcinoma and / or determining whether the ovarian cancer in the subject is primary or secondary ovarian cancer and / or a risk of the disease progression after surgery treatment, and / or an effectiveness of post-surgery chemotherapy.

Description

technical field [0001] The present invention relates to methods for diagnosing and / or prognosing cancer in a subject, particularly but not limited to methods for diagnosing and / or prognosing cancer in a subject by analyzing the MDS1 and EVI1 composite loci (also known as MECO loci) . Background technique [0002] Cancer is one of the leading causes of cancer (death) in the world. Ovarian, cervical and other cancers are very common cancers affecting women worldwide. Among all cancers affecting women, epithelial ovarian cancer (EOC) ranks fifth in cancer mortality among women in the world and fourth in the age group 40-59 years, and overall 5 women with EOC The annual survival rate is only 46%. Nevertheless, it was the advancement of surgical techniques and the emergence of more targeted therapies such as bevacizimab. The low survival rate is explained by a lack of diagnosis of EOC at an early stage, a significant number of patients becoming resistant to chemotherapy over ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q2600/112C12Q1/6886C12Q2600/106C12Q2600/158C12Q2600/118
Inventor 阿尔森·巴特格夫安娜·伊夫希纳弗拉基米尔·库兹涅佐夫
Owner AGENCY FOR SCI TECH & RES
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