CN-122017246-A - Marker for prognosis layering of mucofibrosarcoma and application of marker

CN122017246ACN 122017246 ACN122017246 ACN 122017246ACN-122017246-A

Abstract

The invention discloses a marker for prognosis layering of mucofibrosarcoma and application thereof, and belongs to the technical field of biological medicines. The MDM2 protein or the chromosome 12 multimer has obvious correlation with the prognosis layering of the myxofibrosarcoma, the MDM2 protein or the chromosome 12 multimer is used as a marker of the prognosis layering of the myxofibrosarcoma, and the reagent for detecting the two markers can be applied to judging the prognosis layering of the myxofibrosarcoma. Compared with the markers on the gene level, the markers are easier to detect and interpret in a standardized way through conventional techniques such as immunohistochemistry and the like, and are suitable for developing related prognosis detection reagents.

Inventors

LIU QIUYU
Cang Shundong
HUANG JIANWEI
WANG LONGHAO
GUO XIANGQIAN
XIE QI
LU CHANG
DING YANZHI

Assignees

河南省人民医院

Dates

Publication Date: 20260512
Application Date: 20251208

Claims (8)

1. A marker for prognosis stratification of mucofibrosarcoma, characterized by being MDM2 protein or chromosome 12.
2. Use of an agent for detecting MDM2 protein or chromosome 12 for the preparation of an agent for prognostic stratification of mucofibrosarcoma.
3. Use of a marker for prognosis stratification of mucofibrosarcoma according to claim 1, characterized in that the MDM2 protein positive staining cell number ratio and staining intensity are detected by immunohistochemistry, respectively assigned and the product is calculated as the total score, and prognosis stratification is performed with the total score.
4. The application of the marker for prognosis layering of mucofibrosarcoma according to claim 3, wherein the number of MDM2 protein positive staining cells is counted in an integer, no positive cells are counted as 0 score, the number of positive cells is counted as 1 score less than or equal to 25%, the number of positive cells is counted as 2 score 26% -50%, the number of positive cells is counted as 3 score 51% -75%, and the number of positive cells is counted as 4 score more than or equal to 76%; the dyeing intensity is assigned, wherein the dyeing result is colorless and marked as 0 score, the dyeing result is pale yellow and marked as 1 score, the dyeing result is brown and marked as 2 score, and the dyeing result is brown and marked as 3 score; Calculating the product of the number ratio of MDM2 protein positive staining cells and the staining intensity score to obtain a total score; When the total score is 0-1 score, the grading result is negative, which indicates that the prognosis is good; when the total score is 2-4, the grading result is "+", which indicates that the prognosis is good; when the total score is 5-8, the grading result is "++", which indicates poor prognosis; when the total division is 9-12 minutes, the result of the ranking for "+++", indicating poor prognosis.
5. The use of a marker for prognosis stratification of myxofibrosarcoma according to claim 4, characterized in that at least 10 fields per slice are randomly observed at 400 x Gao Beijing fields, averaged as a result of the slice.
6. Use of a marker for prognosis layering of myxofibrosarcoma according to claim 1, wherein the prognosis layering of myxofibrosarcoma is performed by detecting the copy number of MDM2 gene and the number of chromosome 12 in the myxofibrosarcoma tissue, wherein if MDM2 gene is not amplified and chromosome 12 is multimeric, it indicates poor prognosis.
7. The use of a marker for prognosis layering of mucofibrosarcoma according to claim 6, wherein MDM2 gene copy number and chromosome number 12 are detected by fluorescence in situ hybridization; if the ratio of the copy number of the MDM2 gene to the number of the No. 12 chromosomes is less than 2, the MDM2 gene is not amplified, and if the number of the No. 12 chromosomes/the number of the detected mucofibrosarcoma tumor cells is more than or equal to 3, the number of the No. 12 chromosomes is more than 3; wherein the number of chromosome 12 is determined by the number of chromosome 12 centromeres.
8. The use of a marker for prognosis layering of myxofibrosarcoma according to claim 7, wherein the detection is repeated more than 2 times.

Description

Marker for prognosis layering of mucofibrosarcoma and application of marker Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a marker for prognosis layering of mucofibrosarcoma and application thereof. Background Mucofibrosarcoma (myxofibrosarcoma, MFS) is a rare malignant fibrogenic soft tissue tumor, and has a very low proportion in malignant tumors, which is common in middle-aged and elderly men, and is best found in limbs and trunk. The tumor has higher local recurrence rate, the recurrence rate is different from 22% -79%, and a considerable proportion of recurrence tumors possibly progress to higher pathological grades, and 20% -35% of high-grade cases can also metastasize in blood. Because mucofibrosarcoma generally exhibits complex karyotype characteristics, it is at high risk of local recurrence and metastasis, and at the same time lacks effective targeted detection markers, resulting in undesirable long-term survival of patients. The cytogenetic characteristics of myxofibrosarcoma present a high degree of complexity, with most cases the chromosome number in the triploid or tetraploid range, and with increasing tumor grade, cytogenetic abnormalities tend to increase further. In addition, locally recurrent tumors often exhibit more complex genetic alterations than the primary tumor, suggesting that the tumor is exacerbated by genetic instability during progression. The MDM2 gene as a known negative p53 regulator has been used as an important differential diagnostic marker in hyperdifferentiated or dedifferentiated liposarcoma. In addition, MDM2 amplification is also seen in a few other sarcoma types, including malignant peripheral sphingoma, leiomyosarcoma, etc. However, no study has shown a reliable link between this gene and the prognosis of mucofibrosarcoma. More importantly, from the aspects of clinical applicability and detection stability of the markers, the markers located at protein level or abnormal specific chromosome structure are easier to carry out standardized detection and interpretation by conventional techniques such as immunohistochemistry compared with the markers at gene level, and have better operability in pathological application, so that the markers are also more suitable for developing related prognostic detection reagents. Currently, in the field of mucofibrosarcoma, protein or chromosome level markers that have clear prognostic indicators and facilitate transformation remain lacking. Disclosure of Invention The invention aims to provide a marker for prognosis layering of myxofibrosarcoma and application thereof, so as to solve the problem that protein or chromosome level markers for prognosis layering of myxofibrosarcoma are lacking in the prior art. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: a marker for prognosis stratification of mucofibrosarcoma, which is MDM2 protein or chromosome 12 multimer. Overexpression of MDM2 protein or chromosome 12 multimer indicates a poor prognosis for mucofibrosarcoma. Murine double minichromosome 2 (Murine Double Minute, MDM 2) is a highly amplified gene cloned from a transformed mouse cell line containing double minichromosomes for the first time in 1987, which highly amplified gene promotes cell neoplasia, and the MDM2 gene is located on chromosome 12 long arm 12q15, which is the most well-documented p53 negative regulator. However, in some 12 chromosome-bearing tumors, the 12q15 region fragment was deleted from the chromosome of the multimer, and the actual effective MDM2 gene copy number was not increased. The invention surprisingly found that MDM2 protein overexpression or chromosome 12 multimer has significant correlation with the prognosis layering of myxofibrosarcoma. The recognition that the chromosome 12 multimer in the mucofibrosarcoma that is negative for MDM2 gene amplification is positively correlated with MDM2 protein overexpression indicates that MDM2 protein overexpression in the mucofibrosarcoma is driven by the indirect effect of the chromosome multimer rather than traditional local MDM2 gene amplification, and therefore the chromosome 12 multimer can be used as an important molecular pathogenetic marker for assessing prognosis of MFS patients. The invention also provides the use of a reagent for detecting MDM2 protein or chromosome 12 in the preparation of a reagent for prognosis layering of mucofibrosarcoma. The invention also provides an application of the marker for prognosis layering of the mucofibrosarcoma, the MDM2 protein positive staining cell number proportion and staining intensity are detected through immunohistochemistry, the product is respectively assigned and calculated as a total score, and the prognosis layering is carried out by the total score. The invention is limited by the method, wherein the number of positive staining cells of MDM2 protein is counted by taking the result as an