Pharmaceutical composition for treating endometrial cancer with poor prognosis by preserving fertility function

Abstract

The present invention discloses a pharmaceutical composition for treating endometrial cancer with poor prognosis by preserving fertility function. The pharmaceutical composition provided by the present invention is composed of progestogen and statin. The present invention proves that endometrial cancer patients with poor prognosis after fertility preservation treatment (progestogen treatment) can obtain significant clinical benefits by using progestogen and statin lipid-lowering drugs in combination during the treatment process.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to a pharmaceutical composition for treating endometrial cancer with poor prognosis by preserving fertility. Background Art

[0002] The uterus is the most important organ for women to bear children. Endometrial cancer seriously threatens the reproductive function of young women. In recent years, the incidence of endometrial cancer has continued to rise, and it has a clear trend of younger people. The occurrence of endometrial cancer is closely related to diabetes, obesity, etc., and is considered a metabolic tumor.

[0003] At present, the conventional treatment for endometrial cancer is total hysterectomy, after which the patient will completely lose fertility, so endometrial cancer fertility-preserving treatment has important social significance. At present, the main treatment for endometrial cancer fertility-preserving treatment is progesterone therapy. According to relevant studies, the complete remission rate of endometrial cancer fertility-preserving treatment is 48.2-77.1%, the median complete remission time is 6 months, and the proportion of patients who have not achieved complete remission for more than 6 months of treatment (clinically defined as progesterone-insensitive patients) is about 45.8%, and the proportion of patients who have not achieved complete remission for more than 12 months (clinically defined as progesterone-resistant patients) is about 33.1%. The longer the treatment time, the more obvious the side effects of the drug will be, and it may also increase the risk of late pregnancy failure.

[0004] At present, there is no effective method or biomarker to predict the efficacy of fertility-preserving treatment for endometrial cancer patients, and the population of progesterone-insensitive / resistant people cannot be identified in advance before treatment. Therefore, in the clinical practice of fertility-preserving treatment for endometrial cancer, in order to shorten the treatment time, improve the efficacy, and identify the population of progesterone-insensitive / resistant people, efficient and accurate treatment prognosis evaluation methods are urgently needed. And effective clinical drugs are urgently needed for the population of progesterone-insensitive / resistant people. Summary of the invention

[0005] The purpose of the present invention is to provide a prognosis evaluation system for endometrial cancer fertility-preserving treatment.

[0006] In a first aspect, the present invention claims a pharmaceutical composition for treating progestin-insensitive endometrial cancer.

[0007] The pharmaceutical composition for treating endometrial cancer insensitive to progesterone claimed in the present invention consists of progesterone and statins.

[0008] Wherein, the progestogen is medroxyprogesterone and the statin is atorvastatin.

[0009] In a second aspect, the present invention claims the use of statins in the preparation of a product for enhancing the sensitivity of endometrial cancer patients to progesterone. The present invention also claims the use of statins in enhancing the sensitivity of endometrial cancer patients to progesterone.

[0010] Wherein, the progestogen is medroxyprogesterone and the statin is atorvastatin.

[0011] Wherein, the endometrial cancer patient is an endometrial cancer patient who is insensitive to progesterone.

[0012] In a third aspect, the present invention claims the use of statins as sensitizers in the preparation of a product for treating endometrial cancer in combination with progesterone in a subject, wherein the subject is an endometrial cancer patient who is insensitive to progesterone.

[0013] Wherein, the progestogen is medroxyprogesterone and the statin is atorvastatin.

[0014] In a fourth aspect, the present invention claims the use of progestogen and statin in the preparation of a pharmaceutical composition for treating endometrial cancer that is insensitive to progestogen. The present invention also claims the use of progestogen and statin in the treatment of endometrial cancer that is insensitive to progestogen.

[0015] Wherein, the progestogen is medroxyprogesterone and the statin is atorvastatin.

[0016] In a fifth aspect, the present invention claims a method for treating endometrial cancer that is insensitive to progesterone.

[0017] The method for treating progesterone-insensitive endometrial cancer claimed in the present invention comprises the following steps: administering the pharmaceutical composition described in the first aspect above to a patient with progesterone-insensitive endometrial cancer.

[0018] In a sixth aspect, the present invention claims a method for enhancing the sensitivity of endometrial cancer patients to progesterone, wherein the endometrial cancer patients are endometrial cancer patients insensitive to progesterone.

[0019] The method for enhancing the progesterone sensitivity of endometrial cancer patients claimed in the present invention may include the following steps: administering progesterone treatment to endometrial cancer patients who are insensitive to progesterone and simultaneously administering statins, thereby enhancing the progesterone sensitivity of endometrial cancer patients.

[0020] In the above-mentioned related aspects, the progesterone-insensitive endometrial cancer is endometrial cancer that has not achieved complete remission after seven months of treatment with progesterone alone (such as medroxyprogesterone).

[0021] In the above-mentioned related aspects, the progesterone-insensitive endometrial cancer can be assessed and determined according to any of the following:

[0022] (A1) If the cholesterol ester content in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient insensitive to progesterone; otherwise, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient sensitive to progesterone;

[0023] (A2) If the fat content percentage in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 1.5%, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is insensitive to progesterone; otherwise, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is sensitive to progesterone.

[0024] In the present invention, the percentage of fat content in the tumor tissue is measured by Oil Red O staining. The percentage of fat content in the tumor tissue is equal to the area of ​​the fat droplets divided by the total area of ​​the tumor region.

[0025] In the present invention, the endometrial cancer patient is a stage IA endometrial cancer patient.

[0026] Experimental proof: This application proves that the increased total fat content and cholesterol ester content in the tumor tissue of patients with endometrial cancer are sensitive markers for poor prognosis of endometrial cancer with fertility-sparing treatment (progesterone therapy). The method of the present invention can be used to classify patients with endometrial cancer and predict their prognosis for fertility-sparing treatment (progesterone therapy). Furthermore, for patients with endometrial cancer with a poor prognosis after fertility-sparing treatment (progesterone therapy), the combined use of progesterone and statin lipid-lowering drugs during treatment can achieve significant clinical benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Oil red O staining of tumor tissue and analysis of fat content in tumor tissue in patients with endometrial cancer.

[0028] Figure 2 A retrospective clinical trial (training set) to predict the efficacy of fertility-sparing treatment (progestin therapy) for endometrial cancer.

[0029] Figure 3 This is the correlation analysis between various clinical indicators and the efficacy of fertility-preserving treatment (progestin therapy) (training set).

[0030] Figure 4 A retrospective clinical trial (validation set) to predict the efficacy of fertility-sparing treatment (progestin therapy) for endometrial cancer.

[0031] Figure 5This is a correlation analysis between various clinical indicators and the efficacy of fertility-preserving treatment (progestin therapy) (validation set).

[0032] Figure 6 A randomized controlled trial of progestogen therapy versus combined progestogen and statin lipid-lowering therapy for women with endometrial cancer who have undergone fertility-sparing therapy (progestogen therapy) and have a poor prognosis. DETAILED DESCRIPTION

[0033] The present invention is further described in detail below in conjunction with specific embodiments, and the examples provided are only for illustrating the present invention, rather than for limiting the scope of the present invention. The examples provided below can be used as a guide for further improvements by those of ordinary skill in the art, and do not constitute a limitation of the present invention in any way.

[0034] The experimental methods in the following examples, unless otherwise specified, are all conventional methods, and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial channels.

[0035] The method used in the following examples to detect the percentage (%) of fat content in tumor tissue of endometrial cancer patients is Oil Red O staining.

[0036] The specific steps of Oil Red O staining are as follows: The tumor tissue specimens of endometrial cancer to be tested are directly embedded in OCT (optimal cutting temperature compound, Sakura #4583) to prepare frozen sections with a thickness of 10 μm. The frozen sections are stained using the Oil Red O staining kit (Solabo #G1261) according to the following steps: (1) Wash twice with distilled water for 3 minutes each time; (2) Wash the sections in 60% isopropanol for 30 seconds; (3) Wash the sections in modified Oil Red O staining solution (covered) and seal for 15 minutes; (4) Wash the sections in 60% isopropanol for 5 seconds to remove the staining solution and wash with running water for 1 minute; (5) Counterstain the nucleus with Mayer's hematoxylin staining solution for 2 minutes; (6) Rinse with tap water for 10 minutes to reverse blue; (7) Wash once with distilled water and dry the surrounding water with filter paper; (8) Seal the sections with glycerol gelatin.

[0037] The staining effect of Oil Red O is shown in Figure 1The steps for staining image data analysis are as follows: (1) Scan the stained slides with a slice scanner (Shengqiang SQS-40P) at a scanning magnification of 40×. Select three tumor sites for each slice and capture the field of view. The field of view area is 7019 pixels × 3410 pixels; (2) Open the image with ImageJ software and use the RBG color separation function to obtain the blue channel field of view image; (3) Use the threshold function to process the image and set the threshold to 0-90; (4) Use the Measure function to measure the image and obtain the area of ​​lipid droplets; (5) Divide the area of ​​lipid droplets by the total area of ​​the tumor region to obtain the percentage of fat content in the tumor tissue. The average percentage of fat content in the three fields of view is output as the detection value.

[0038] The method used in the following examples for detecting the content of cholesterol ester (μmol / g) in tumor tissue of patients with endometrial cancer is as follows: (1) prepare a standard substance (5.17 mmol / L cholesterol standard substance) according to the instructions of the cholesterol ester content detection kit (Elerite #E-BC-F032); (2) weigh and homogenize the tumor tissue of the patient with endometrial cancer to be tested, and dilute the homogenate to 300 μL; (3) set a standard well, a test well and a blank control well in a 96-well ELISA plate, and the sample volume of each well is 50 μL; (4) add 50 μL of color developer 1 to each well, shake the plate for 10 seconds, and incubate at 37°C in the dark for 10 min. The fluorescence value of each well at an excitation wavelength of 535 nm and an emission wavelength of 590 nm was detected on an ELISA reader (Synergy LX) to obtain the total cholesterol content in the sample; (5) The standard wells, test wells and blank control wells were reset, and the sample volume of each well was 50 μL; (6) 50 μL of color developer 2 was added to each well, the plate was shaken for 10 seconds, and incubated at 37°C in the dark for 10 minutes. The fluorescence value of each well at an excitation wavelength of 535 nm and an emission wavelength of 590 nm was detected on an ELISA reader (Synergy LX) to obtain the free cholesterol content in the sample; (7) The cholesterol ester content was obtained by subtracting the free cholesterol content from the total cholesterol content, and this content was divided by the tissue weight to obtain the cholesterol ester content per gram of tumor tissue.

[0039] The inclusion criteria for endometrial cancer cases in the following examples are: (1) patients under 45 years old with a strong desire to preserve fertility; (2) the histopathological type is endometrial adenocarcinoma, well-differentiated (G1 / G2); (3) imaging examinations confirm that the tumor is confined to the endometrium, without extrauterine invasion and lymph node metastasis; (4) histopathological detection of progesterone receptor positivity; (5) fully informed consent and good follow-up conditions.

[0040] The criteria for grouping endometrial cancer cases in the following examples are as follows: (1) those with fertility disorders and contraindications; (2) those whose pre-treatment evaluation indicates cervical infiltration, extrauterine invasion, or lymph node metastasis; (3) those with contraindications to progestin therapy; (4) those with a family history of hereditary tumors such as Lynch syndrome; (5) those with combined malignant tumors in other parts of the body; and (6) those with poor compliance, inability to cooperate with clinical treatment, and inability to bear the risks associated with treatment.

[0041] Example 1: Establishment of a prognosis prediction cohort for endometrial cancer fertility-sparing treatment (progestin therapy)

[0042] like Figure 2 The present invention established a retrospective clinical trial to identify factors related to the prognosis of fertility-preserving therapy (progestin therapy) for endometrial cancer. A total of 40 patients with endometrial cancer in stage IA who were interested in fertility-preserving therapy were enrolled. Except for one patient who gave up fertility-preserving therapy, the remaining 39 patients collected peripheral blood and tumor biopsy samples before treatment and performed relevant tests. The test indicators and results are shown in Table 1. Subsequently, these patients were treated with fertility-preserving therapy (progestin therapy, specifically medroxyprogesterone, 500 mg / day, taken orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines), and follow-up and efficacy evaluation were performed in the third and seventh months of the treatment process, and the patients were divided into a sensitive group (13 patients) and an insensitive group (26 patients) based on whether complete remission could be achieved after seven months of treatment.

[0043]

[0044]

[0045] The occurrence of endometrial cancer is closely related to diabetes and obesity. Therefore, the present invention detects relevant indicators of the enrolled patients, including: the proportion of fat content in tumor tissue, the cholesterol ester content in tumor tissue, lipid accumulation index, visceral fat index, body mass index, high-density lipoprotein, low-density lipoprotein, and free fatty acids.

[0046] The above parameters were analyzed for correlation with the clinical outcomes of the patients' fertility preservation treatment (progestin therapy). Figure 3As shown. It can be seen that in this clinical trial cohort (training set cohort), the area under the ROC curve of the correlation curve between the proportion of fat content in tumor tissue and prognosis is 0.824 (p=0.0011), and the two are significantly correlated; the area under the ROC curve of the correlation curve between the cholesterol ester content in tumor tissue and prognosis is 0.959 (p<0.0001), and the two are significantly correlated; the area under the ROC curve of the correlation curve between high-density lipoprotein and prognosis is 0.783 (p=0.0044), and the two are significantly correlated. However, parameters such as lipid accumulation index, visceral fat index, body mass index, blood sugar, low-density lipoprotein and free fatty acids are not significantly correlated with treatment and after. Detailed data are shown in Table 2.

[0047]

[0048] According to the ROC curve of the indicator "percentage of fat content in tumor tissue", the optimal cutoff value was determined to be 1.5%. Under this condition, combined with the clinical outcomes, we analyzed and obtained Table 3.

[0049]

[0050] That is, if the fat content in the tumor tissue of the endometrial cancer patient to be tested accounts for less than 1.5%, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is sensitive to progesterone; if the fat content in the tumor tissue of the endometrial cancer patient to be tested accounts for greater than or equal to 1.5%, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is insensitive to progesterone.

[0051] The sensitivity and specificity of the method for predicting poor prognosis using "tumor tissue fat content ratio" are:

[0052] Sensitivity = true positive / (true positive + false negative) = 18 / (18+8) = 69.2%;

[0053] Specificity = true negative / (true negative + false positive) = 11 / (11+2) = 84.6%.

[0054] According to the ROC curve of the indicator "tumor tissue cholesterol ester content", the optimal cutoff value was determined to be 40 μmol / g. Under this condition, combined with the clinical outcomes, the analysis was performed to obtain Table 4.

[0055]

[0056] That is, if the cholesterol ester content in the tumor tissue of the endometrial cancer patient to be tested is less than 40 μmol / g, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient sensitive to progesterone; if the cholesterol ester content in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient insensitive to progesterone.

[0057] The sensitivity and specificity of the method for predicting poor prognosis using "tumor tissue cholesterol ester content" are:

[0058] Sensitivity = true positive / (true positive + false negative) = 22 / (22+4) = 84.6%;

[0059] Specificity = true negative / (true negative + false positive) = 13 / (13 + 0) = 100%.

[0060] According to the ROC curve of the indicator "high-density lipoprotein content", the optimal cutoff value was determined to be 1.1 mmol / L. Under this condition, combined with the clinical outcomes, the analysis was performed to obtain Table 5.

[0061]

[0062] That is, if the high-density lipoprotein content in the peripheral blood of the endometrial cancer patient to be tested is greater than 1.1 mmol / L, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is sensitive to progesterone; if the high-density lipoprotein content in the peripheral blood of the endometrial cancer patient to be tested is less than or equal to 1.1 mmol / L, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is insensitive to progesterone.

[0063] The sensitivity and specificity of the method for predicting poor prognosis using "high-density lipoprotein content" are:

[0064] Sensitivity = true positive / (true positive + false negative) = 19 / (19+7) = 73.1%;

[0065] Specificity = true negative / (true negative + false positive) = 10 / (10+3) = 76.9%.

[0066] Based on the data obtained from the above clinical trials, the present invention selected three parameters, namely the percentage of fat content in tumor tissue, the cholesterol ester content in tumor tissue and the high-density lipoprotein content in peripheral blood, as sensitive markers for poor prognosis of endometrial cancer with fertility-preserving treatment (progestin therapy), for further testing in subsequent verification cohorts.

[0067] Example 2: Validation cohort of sensitive markers for poor prognosis in endometrial cancer patients undergoing fertility-sparing therapy (progestin therapy)

[0068] like Figure 4The present invention established a retrospective clinical trial to identify the three biomarkers selected in Example 1 and the factors related to the treatment prognosis of endometrial cancer fertility preservation therapy (progestin therapy). A total of 30 patients with endometrial cancer in stage IA who intended to undergo fertility preservation therapy were enrolled (an independent sample set completely different from the training set in Example 1). Except for one person who gave up fertility preservation therapy, the remaining 29 patients collected peripheral blood and tumor biopsy samples before treatment and performed relevant tests. The test indicators and results are shown in Table 6. Subsequently, these patients were treated with fertility preservation therapy (progestin therapy, specifically medroxyprogesterone, 500 mg / day, orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines), and follow-up and efficacy evaluation were performed in the third and seventh months of the treatment process, and the patients were divided into sensitive and insensitive groups based on whether complete remission could be achieved after seven months of treatment.

[0069]

[0070] It can be seen that in this clinical trial cohort (validation set cohort), the area under the ROC curve of the correlation curve between fat content in tumor tissue and prognosis is 0.745 (p=0.0253), and the two are significantly correlated; the area under the ROC curve of the correlation curve between cholesterol ester content in tumor tissue and prognosis is 0.899 (p=0.0003), and the two are significantly correlated; the area under the ROC curve of the correlation curve between high-density lipoprotein and prognosis is 0.608 (p=0.324), and there is no correlation between the two. Results and detailed data are shown in Figure 5 and Table 7.

[0071]

[0072] Next, we verified the sensitivity and specificity of the cutoff value of 15% of the "tumor tissue fat content ratio" indicator obtained in Example 1 in the validation cohort. The validation set data is shown in Table 8.

[0073]

[0074] Sensitivity = true positive / (true positive + false negative) = 10 / (10+6) = 62.5%;

[0075] Specificity = true negative / (true negative + false positive) = 9 / (9+4) = 69.2%.

[0076] Next, we obtained the sensitivity and specificity of the cutoff value of 40 μmol / g of the indicator "tumor tissue cholesterol ester content" in Example 1 in the validation cohort. The validation set data is shown in Table 9.

[0077]

[0078] Sensitivity = true positive / (true positive + false negative) = 15 / (15+1) = 93.8%;

[0079] Specificity = true negative / (true negative + false positive) = 11 / (11+2) = 84.6%.

[0080] According to the data obtained from the above clinical trials, the present invention finally confirmed that the two parameters of "tumor tissue fat content ratio" and "tumor tissue cholesterol ester content" can be used as sensitive markers for poor prognosis of endometrial cancer fertility preservation treatment (progesterone therapy). Among them, the "tumor tissue cholesterol ester content" indicator has high sensitivity and specificity for predicting poor prognosis, and is an efficient and accurate prediction indicator; "tumor tissue fat content ratio" is correlated with prognosis, but the sensitivity and specificity of using this indicator to predict poor prognosis are relatively low.

[0081] Example 3: A randomized controlled clinical trial of fertility-sparing treatment (progestin therapy) for endometrial cancer patients with poor prognosis: progestin therapy versus combined treatment with progestin and statin lipid-lowering drugs

[0082] like Figure 6 The present invention establishes a randomized controlled clinical trial to verify the effectiveness of combined treatment of progesterone and statin lipid-lowering drugs for people who are not sensitive to progesterone treatment. A total of 58 patients with endometrial cancer in stage IA who intend to undergo fertility preservation treatment were enrolled. Among them, 4 patients were grouped due to loss of follow-up, and 3 patients gave up the fertility preservation treatment group. The remaining 51 patients were biopsied according to the methods in Example 1 and Example 2, and the total fat content and cholesterol ester content in the tumor tissue were detected. Based on this, the patients were divided into a progesterone sensitive group (13 people, the cholesterol ester content in the tumor tissue was less than 40μmol / g and the fat content in the tumor tissue accounted for less than 1.5%) and a progesterone insensitive group (38 people, the cholesterol ester content in the tumor tissue was greater than or equal to 40μmol / g and the fat content in the tumor tissue accounted for greater than or equal to 1.5%). Among them, 13 people in the sensitive group were treated with fertility preservation treatment (progesterone treatment, specifically medroxyprogesterone, 500mg / day, taken orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines) and the efficacy was observed. The insensitive group was randomly divided into two groups. The experimental group received a combination of progesterone (medroxyprogesterone, 500 mg / day, taken orally once a day) and statin (atorvastatin, 20 mg / day, taken orally once a day), and the control group received fertility-preserving treatment (progesterone treatment, specifically medroxyprogesterone, 500 mg / day, taken orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines). The enrolled patients were followed up and the efficacy was evaluated in the third and seventh months of the treatment.

[0083] It can be seen that among the 13 patients in the sensitive group, except for 3 patients who were treated for less than three months and whose efficacy could not be evaluated temporarily, 9 of the remaining 10 patients achieved complete remission in seven months, and 1 patient achieved partial remission in the seventh month. Among the 38 patients in the insensitive group, except for 4 patients who were treated for less than three months and whose efficacy could not be evaluated temporarily, 15 patients who completed the efficacy evaluation did not achieve complete remission after 3 months of treatment, among whom 3 patients achieved complete remission after 7 months of treatment, and the remaining 12 patients still did not achieve complete remission after 7 months of treatment. These further confirm that this method can accurately predict the efficacy of progestin conservation therapy.

[0084] Of the 19 patients in the experimental group, 8 achieved complete remission after 3 months of treatment, and another 8 achieved complete remission after 7 months of treatment, except for 3 patients who were not treated for 3 months and could not be evaluated for efficacy. These results show that this method predicts that patients who are insensitive to progesterone therapy can benefit from adding statin lipid-lowering drugs.

[0085] The present invention has been described in detail above. For those skilled in the art, without departing from the purpose and scope of the present invention, and without the need to carry out unnecessary experimental conditions, the present invention can be implemented in a wide range under equivalent parameters, concentrations and conditions. Although the present invention provides specific embodiments, it should be understood that the present invention can be further improved. In a word, according to the principles of the present invention, the application is intended to include any changes, uses or improvements to the present invention, including departure from the disclosed scope in the application, and changes made with conventional techniques known in the art.

Claims

1. A pharmaceutical composition for treating endometrial cancer insensitive to progesterone, comprising a progesterone and a statin.

2. The pharmaceutical composition according to claim 1, characterized in that: The progestogen is medroxyprogesterone; and / or The statin is atorvastatin.

3. Use of progestogen and statins in the preparation of a pharmaceutical composition for treating endometrial cancer that is insensitive to progestogen.

4. The use according to claim 3, characterized in that: The progestogen is medroxyprogesterone; and / or The statin is atorvastatin.

5. The use according to claim 3, characterized in that: The progesterone-insensitive endometrial cancer is an endometrial cancer that has not achieved complete remission after seven months of progesterone-only treatment.

6. The use according to claim 3, characterized in that: The progestin-insensitive endometrial cancer is determined by evaluating any of the following: (A1) If the cholesterol ester content in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient insensitive to progesterone; otherwise, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient sensitive to progesterone; (A2) If the fat content percentage in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 1.5%, the endometrial cancer patient to be tested is deemed to be an endometrial cancer patient who is insensitive to progesterone; Otherwise, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is sensitive to progesterone.

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