Pituitary tumor TPIT pedigree classification method based on gene ESRP1 expression quantity
By measuring the expression of the gene ESRP1 in pituitary tumors and establishing a threshold, accurately distinguishing between functional and non-functional ACTH subtypes in the TPIT lineage, the problem of distinguishing difficulties in the prior art was solved, and the treatment effect and quality of life were improved.
Patent Information
- Application Number
- CN202510032249.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-09
- Publication Date
- 2025-05-13
AI Technical Summary
The prior art is difficult to effectively distinguish between functional and non-functional ACTH subtypes in the TPIT lineage of pituitary tumors, resulting in inconsistent treatment response and high risk of recurrence.
By measuring the expression amount of gene ESRP1, an ESRP1 expression threshold was established to distinguish between functional and non-functional ACTH subtypes in the TPIT lineage. The specific method includes extracting RNA for PCR amplification, obtaining ESRP1 expression value, and making subtype judgment based on the threshold.
Accurate classification of the TPIT lineage subtype of pituitary tumors is achieved, helping to formulate personalized treatment strategies, improve treatment effects and patient quality of life, and reduce the risk of recurrence of non-functional ACTH subtypes.
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Figure CN119979709A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of pituitary tumor subtype identification, and specifically relates to a TPIT lineage classification method for pituitary tumors based on the expression amount of gene ESRP1. Background Art
[0002] TPIT spectrum tumors mainly include two subtypes, functional corticotroph tumors and non-functional corticotroph tumors. Different subtypes of tumors have different aggressiveness, hormone secretion characteristics, and responses to treatment. For example, non-functional corticotroph tumors are more aggressive and have a high recurrence rate. For this type of tumor, long-term monitoring is required.
[0003] At present, the main clinical methods for TPIT spectrum classification are histopathological examination and hormone level detection. Histopathological examination is to detect TPIT and ACTH expression through immunohistochemistry (IHC). Hormone level detection is to detect the levels of adrenocorticotropic hormone and cortisol in plasma, but some patients with non-functional adrenocorticotropic cell tumors will also have abnormally elevated levels of adrenocorticotropic hormone.
[0004] In addition, imaging and clinical information can be used to assist in the distinction. Most functional adrenocorticotrophoblastomas are microadenomas, about 5%-10% of patients have large tumors, and silent adrenocorticotrophoblastomas often present as invasive large tumors. Patients with functional adrenocorticotrophoblastomas have typical manifestations of Cushing's disease, but many symptoms and signs of Cushing's disease, such as obesity and hypertension, are common in the general population, so further division of the TPIT spectrum remains challenging. Summary of the invention
[0005] In order to solve the above-mentioned technical problems, the expression of gene ESRP1 is used to further divide the TPIT spectrum of pituitary tumors into subtypes, and the prognosis of patients with pituitary tumors is timely understood. The present invention provides a classification method for the TPIT spectrum of pituitary tumors based on the expression of gene ESRP1, which provides valuable clues for the diagnosis and treatment of the disease.
[0006] The technical solutions adopted are as follows:
[0007] A method for classifying the TPIT spectrum of pituitary tumors based on the expression of gene ESRP1, comprising the steps of obtaining samples of patients with TPIT spectrum of pituitary tumors; extracting RNA from sample tissues and performing PCR amplification experiments to obtain the ESRP1 expression value of gene ESRP1 in the TPIT spectrum of pituitary tumors; establishing an ESRP1 expression threshold for distinguishing functional ACTH and non-functional ACTH subtypes in the TPIT spectrum according to the ESRP1 expression value of the TPIT spectrum patient samples; and determining the TPIT spectrum subtype of the pituitary tumor of the patient to be tested according to the ESRP1 expression value of the gene ESRP1 of the patient to be tested and the ESRP1 expression threshold.
[0008] Furthermore, the ESRP1 expression threshold established for distinguishing functional ACTH and non-functional ACTH subtypes in the TPIT spectrum is an mRNA relative expression threshold, and its value range is 0.7-0.8; when the mRNA relative expression level of the gene ESRP1 of the obtained TPIT spectrum patient sample is lower than the mRNA relative expression threshold, the TPIT spectrum patient sample is judged to be a non-functional ACTH subtype; when the mRNA relative expression level of the gene ESRP1 of the obtained TPIT spectrum patient sample is higher than the mRNA relative expression threshold, the TPIT spectrum patient sample is judged to be a functional ACTH subtype.
[0009] Or further, the ESRP1 expression threshold established for distinguishing functional ACTH and non-functional ACTH subtypes in the TPIT spectrum is the ESRP1 expression dynamic CT threshold; by measuring the CT value of the pituitary tumor patient to be tested, the obtained CT value is compared with the constructed ESRP1 expression dynamic CT threshold, and the subtype of the pituitary tumor sample to be tested is distinguished.
[0010] Preferably, a pituitary tumor sample is obtained, RNA of the sample tissue is extracted and reverse transcribed into cDNA; a CT value representing the expression amount of the gene ESRP1 is obtained by PCR amplification with ESRP1 primers; the obtained CT value is compared with the constructed ESRP1 expression dynamic CT threshold value to distinguish the subtype of the pituitary tumor sample to be tested.
[0011] Preferably, the established dynamic CT threshold of ESRP1 expression is 25-26.5.
[0012] Furthermore, when the measured CT value is lower than the dynamic CT threshold of ESRP1 expression, the measured pituitary tumor sample is functional ACTH, and when the measured CT value is higher than the dynamic CT threshold of ESRP1 expression, the measured pituitary tumor sample is non-functional ACTH.
[0013] The technical effects produced by the solution of the present invention are as follows:
[0014] A. The present invention can quickly provide patients with more individualized treatment strategies by correctly classifying the subtypes of TPIT-spectrum pituitary tumors, thereby improving the treatment effect and the quality of life of patients. For the differentiated functional ACTH pituitary tumors, the key to treatment is to control ACTH secretion and cortisol levels, which requires controlling hormone levels and combining drug and surgical treatment; while for non-functional ACTH pituitary tumors, the treatment is mainly focused on removing the tumor and relieving compression symptoms.
[0015] B. The method of the present invention can be used to correctly distinguish the TPIT spectrum pituitary tumor subtypes, and can also help evaluate the patient's prognosis. For patients with non-functional ACTH pituitary tumors, due to the high risk of recurrence, long-term follow-up examinations are required to ensure that the tumor has not recurred or spread.
[0016] C. The present invention measures the relative mRNA expression or CT value of pituitary tumor patients, combines the established mRNA relative expression threshold and the ESRP1 expression dynamic CT threshold, and compares them respectively, so as to quickly classify the pituitary tumor subtypes of the TPIT spectrum. Of course, the two can also be combined for judgment, with high accuracy. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] In order to more clearly illustrate the specific embodiments of the present invention, the drawings required for use in the specific embodiments will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.
[0018] Figure 1 It is a flow chart of the TPIT lineage classification method for pituitary tumors provided by the present invention. DETAILED DESCRIPTION
[0019] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0020] like Figure 1 As shown, the present invention provides a method for classifying pituitary tumor subtypes based on alternative splicing features, which specifically includes the following steps:
[0021]
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[0025] The ESRP1 expression threshold used here is the mRNA relative expression threshold, and its value range is 0.7-0.8; when the mRNA relative expression of the gene ESRP1 of the TPIT spectrum patient sample obtained is lower than the mRNA relative expression threshold, the TPIT spectrum patient sample is judged to be a non-functional ACTH subtype; when the mRNA relative expression of the gene ESRP1 of the TPIT spectrum patient sample obtained is higher than the mRNA relative expression threshold, the TPIT spectrum patient sample is judged to be a functional ACTH subtype.
[0026] The present invention compares the mRNA relative expression of the obtained gene ESRP1 with the mRNA relative expression threshold of the established gene ESRP1, and divides the pituitary tumor TPIT spectrum into functional ACTH and non-functional ACTH subtypes, and the functional ACTH usually has a better prognosis than the non-functional ACTH subtype. By accurately dividing the pituitary tumor TPIT spectrum into functional and non-functional subtypes through the method of the present invention, an effective treatment strategy can be better formulated to ensure that the tumor does not recur or spread.
[0027] Of course, the ESRP1 expression threshold established for distinguishing functional ACTH and non-functional ACTH subtypes in the TPIT spectrum can also be the ESRP1 expression dynamic CT threshold. By measuring the CT value of the pituitary tumor patient to be tested and comparing the obtained CT value with the constructed ESRP1 expression dynamic CT threshold, the subtype of the pituitary tumor sample to be tested can be distinguished.
[0028] The Ct value (Cycle Threshold) here refers to the cycle number corresponding to when the fluorescence signal of the amplified product reaches the set threshold during the qPCR amplification process, that is, the cycle number corresponding to when the starting template is amplified to a certain amount of product.
[0029] The ESRP1 expression dynamic CT threshold constructed by the present invention is 25-26.5. When the gene ESRP1 expression value of the obtained TPIT spectrum patient sample is lower than the ESRP1 expression dynamic CT threshold, the TPIT spectrum patient sample is determined to be a non-functional ACTH subtype; when the gene ESRP1 expression value of the obtained TPIT spectrum patient sample is higher than the ESRP1 expression dynamic CT threshold, the TPIT spectrum patient sample is determined to be a functional ACTH subtype.
[0030] The following is a validation of tumor samples from three patients with pituitary tumors. Among the three patients, one patient's sample type was a functional ACTH subtype, and the other two patients were non-functional ACTH subtypes. qRT-PCR shows the CT values normalized to GAPDH and the relative mRNA expression of ESRP1 in patients with functional (n=1) and non-functional ACTH subtypes (n=2), as shown in the following table.
[0031]
[0032] It can be seen from this that by obtaining samples from patients with pituitary tumors, RNA from the sample tissue is extracted and reverse transcribed into cDNA; by PCR amplification of ESRP1 primers, a CT value representing the expression of the gene ESRP1 is obtained; the obtained CT value is compared with the constructed ESRP1 expression dynamic CT threshold to distinguish the subtype of the pituitary tumor sample to be tested. When the measured CT value is lower than the CT threshold, the pituitary tumor sample measured is a functional ACTH, and when the measured CT value is higher than the CT threshold, the pituitary tumor sample measured is a non-functional ACTH. While the present invention uses the ESRP1 expression dynamic CT threshold and the mRNA relative expression threshold alone to determine the subtype of pituitary tumors, the two can of course be combined, which will not be repeated here.
[0033] The method of the present invention can distinguish the subtypes of pituitary tumor samples to be tested, accurately obtain the subtype of the pituitary tumor patient to be tested, and then through precise pedigree classification, a more personalized treatment plan can be formulated, thereby improving the treatment effect and the patient's quality of life, and has great promotion value.
[0034] Anything not described in the present invention is applicable to the prior art.
[0035] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. However, the obvious changes or modifications derived therefrom are still within the scope of protection of the present invention.
Claims
1. A method for classifying the TPIT lineage of pituitary tumors based on the expression of the gene ESRP1, characterized in that: Obtain samples from several patients with TPIT spectrum of pituitary tumors; extract RNA from sample tissues and perform PCR amplification experiments to obtain the ESRP1 expression value of the gene ESRP1 in the TPIT spectrum of pituitary tumors; establish an ESRP1 expression threshold for distinguishing functional ACTH and non-functional ACTH subtypes in the TPIT spectrum based on the ESRP1 expression value of the TPIT spectrum patient samples; determine the TPIT spectrum subtype of the pituitary tumor of the patient to be tested based on the ESRP1 expression value of the gene of the patient to be tested and the ESRP1 expression threshold.
2. The method for TPIT lineage classification of pituitary tumors based on the expression of gene ESRP1 according to claim 1, characterized in that: The ESRP1 expression threshold established for distinguishing functional ACTH and non-functional ACTH subtypes in the functional TPIT spectrum is the mRNA relative expression threshold, and its value range is 0.7-0.8; when the mRNA relative expression level of the gene ESRP1 of the obtained TPIT spectrum patient sample is lower than the mRNA relative expression threshold, the TPIT spectrum patient sample is judged to be the non-functional ACTH subtype; when the mRNA relative expression level of the gene ESRP1 of the obtained TPIT spectrum patient sample is higher than the mRNA relative expression threshold, the TPIT spectrum patient sample is judged to be the functional ACTH subtype.
3. The method for TPIT lineage classification of pituitary tumors based on gene ESRP1 expression according to claim 1, characterized in that: The ESRP1 expression threshold established for distinguishing functional ACTH and non-functional ACTH subtypes in the TPIT spectrum is the ESRP1 expression dynamic CT threshold; by measuring the CT value of the pituitary tumor patient to be tested, the obtained CT value is compared with the constructed ESRP1 expression dynamic CT threshold to distinguish the subtype of the pituitary tumor sample to be tested.
4. The method for TPIT lineage classification of pituitary tumors based on the expression of gene ESRP1 according to claim 3, characterized in that: Pituitary tumor samples were obtained, RNA of the sample tissue was extracted and reverse transcribed into cDNA; CT values representing the expression of gene ESRP1 were obtained through PCR amplification with ESRP1 primers; the obtained CT values were compared with the constructed dynamic CT threshold of ESRP1 expression to distinguish the subtypes of the pituitary tumor samples to be tested.
5. The method for TPIT lineage classification of pituitary tumors based on the expression of gene ESRP1 according to claim 4, characterized in that: The established dynamic CT threshold for ESRP1 expression was 25-26.
5.
6. The method for TPIT lineage classification of pituitary tumors based on the expression of gene ESRP1 according to claim 5, characterized in that: When the measured CT value is lower than the dynamic CT threshold of ESRP1 expression, the measured pituitary tumor sample is functional ACTH; when the measured CT value is higher than the dynamic CT threshold of ESRP1 expression, the measured pituitary tumor sample is non-functional ACTH.