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CN118091141B - Application of GLIPR2 detection reagent in the preparation of drug resistance diagnostic reagent for peritoneal metastasis of ovarian cancer - Google Patents

Application of GLIPR2 detection reagent in the preparation of drug resistance diagnostic reagent for peritoneal metastasis of ovarian cancer Download PDF

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CN118091141B
CN118091141B CN202410254084.5A CN202410254084A CN118091141B CN 118091141 B CN118091141 B CN 118091141B CN 202410254084 A CN202410254084 A CN 202410254084A CN 118091141 B CN118091141 B CN 118091141B
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ovarian cancer
peritoneal metastasis
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杨卓
郎廷元
杨牧垚
黄灿华
邱琳
冯静
刘畅
郎廷秀
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Liaoning Cancer Hospital and Institute
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Abstract

本发明涉及检验诊断领域,具体为GLIPR2检测试剂在制备卵巢癌腹膜转移耐药性诊断试剂中的应用。卵巢癌腹膜转移指卵巢癌细胞转移至腹膜形成一个或多个转移病灶的情况,准确判断耐药性具有避免无效新辅助化疗和避免无效化疗两个重要意义,但尚无有效标志物。本发明通过研究发现GLIPR2具有作为卵巢癌腹膜转移耐药性诊断标志物的性质,其蛋白表达检测试剂可用于卵巢癌腹膜转移耐药性诊断试剂的制备。本发明为制备卵巢癌腹膜转移诊断试剂提供了一种新方法。

The present invention relates to the field of testing and diagnosis, and specifically to the use of a GLIPR2 detection reagent in the preparation of a diagnostic reagent for drug resistance in peritoneal metastasis of ovarian cancer. Peritoneal metastasis of ovarian cancer refers to the situation in which ovarian cancer cells metastasize to the peritoneum to form one or more metastatic lesions. Accurately judging drug resistance has two important meanings of avoiding ineffective neoadjuvant chemotherapy and avoiding ineffective chemotherapy, but there is no effective marker. The present invention has found through research that GLIPR2 has the properties of a diagnostic marker for drug resistance in peritoneal metastasis of ovarian cancer, and its protein expression detection reagent can be used for the preparation of a diagnostic reagent for drug resistance in peritoneal metastasis of ovarian cancer. The present invention provides a new method for preparing a diagnostic reagent for peritoneal metastasis of ovarian cancer.

Description

GLIPR2检测试剂在制备卵巢癌腹膜转移耐药性诊断试剂中的 应用Application of GLIPR2 detection reagent in the preparation of drug resistance diagnostic reagent for peritoneal metastasis of ovarian cancer

技术领域Technical Field

本发明涉及检验诊断领域,具体为GLIPR2检测试剂在制备卵巢癌腹膜转移耐药性诊断试剂中的应用。The present invention relates to the field of testing and diagnosis, and specifically to application of a GLIPR2 detection reagent in the preparation of a drug resistance diagnosis reagent for ovarian cancer peritoneal metastasis.

背景技术Background Art

卵巢癌的死亡率在妇科恶性肿瘤中居第一位,主要原因在于其易发生腹膜转移,进而发展到远端器官转移。卵巢癌腹膜转移即指原发性卵巢癌转移至腹膜形成一个或多个腹膜转移病灶的疾病。卵巢癌腹膜转移的主要治疗方法为新辅助化疗和手术治疗,新辅助化疗的主要作用为在手术前缩小或消除病灶,以保证手术的效果。卵巢癌腹膜转移也可选择先手术后化疗。但无论如何使用,新辅助化疗或化疗对具有耐药性质的卵巢癌腹膜转移细胞效果甚微,不仅达不到治疗效果,还使病人因承受药物副作用降低了生存质量。因此,建立卵巢癌腹膜转移耐药性诊断方法对促进卵巢癌的治疗水平至关重要,但目前尚无有效的标志物。The mortality rate of ovarian cancer ranks first among gynecological malignancies, mainly because it is prone to peritoneal metastasis and then develops into distant organ metastasis. Peritoneal metastasis of ovarian cancer refers to the disease in which primary ovarian cancer metastasizes to the peritoneum to form one or more peritoneal metastasis lesions. The main treatments for peritoneal metastasis of ovarian cancer are neoadjuvant chemotherapy and surgical treatment. The main function of neoadjuvant chemotherapy is to shrink or eliminate the lesions before surgery to ensure the effectiveness of the surgery. Ovarian cancer peritoneal metastasis can also choose surgery first and then chemotherapy. However, no matter how it is used, neoadjuvant chemotherapy or chemotherapy has little effect on ovarian cancer peritoneal metastasis cells with drug resistance. Not only does it fail to achieve the therapeutic effect, but it also reduces the quality of life of patients due to the side effects of the drugs. Therefore, it is crucial to establish a diagnostic method for drug resistance of peritoneal metastasis of ovarian cancer to promote the treatment level of ovarian cancer, but there are currently no effective markers.

发现并鉴定标志物是建立一种诊断方法的基础,同时多个标志物的组合可提高诊断方法的准确率,因此,新标志物的鉴定和应用是推动疾病诊断方法发展的基本工作。Discovering and identifying markers is the basis for establishing a diagnostic method. At the same time, the combination of multiple markers can improve the accuracy of the diagnostic method. Therefore, the identification and application of new markers is the basic work to promote the development of disease diagnostic methods.

本发明通过蛋白质组学研究及后续研究发现GLIPR2具备作为诊断卵巢癌腹膜转移耐药性标志物的性质,因此,GLIPR2检测试剂可用于卵巢癌腹膜转移耐药性诊断试剂的制备。本发明为卵巢癌腹膜转移耐药性诊断方法的开发提供了新的策略。The present invention finds through proteomics research and subsequent research that GLIPR2 has the property of being a marker for diagnosing drug resistance in peritoneal metastasis of ovarian cancer. Therefore, the GLIPR2 detection reagent can be used for the preparation of a diagnostic reagent for drug resistance in peritoneal metastasis of ovarian cancer. The present invention provides a new strategy for the development of a diagnostic method for drug resistance in peritoneal metastasis of ovarian cancer.

发明内容Summary of the invention

有鉴于此,本发明的目的在于提供一种GLIPR2检测试剂在制备卵巢癌腹膜转移耐药性诊断试剂中的应用。In view of this, the object of the present invention is to provide an application of a GLIPR2 detection reagent in the preparation of a diagnostic reagent for drug resistance of ovarian cancer peritoneal metastasis.

为达到上述目的,本发明提供如下技术方案:In order to achieve the above object, the present invention provides the following technical solutions:

GLIPR2检测试剂在制备卵巢癌腹膜转移耐药性诊断试剂中的应用。Application of GLIPR2 detection reagent in the preparation of diagnostic reagents for drug resistance of ovarian cancer peritoneal metastasis.

本发明优选的,所述卵巢癌腹膜转移指原发性卵巢癌转移至腹膜形成一个或多个腹膜转移病灶的疾病。Preferably, the ovarian cancer peritoneal metastasis refers to a disease in which primary ovarian cancer metastasizes to the peritoneum to form one or more peritoneal metastatic lesions.

本发明优选的,所述卵巢癌腹膜转移耐药性指原发卵巢癌腹膜转移灶癌细胞对铂类药物的耐药性。Preferably, the ovarian cancer peritoneal metastasis drug resistance of the present invention refers to the drug resistance of primary ovarian cancer peritoneal metastasis cancer cells to platinum drugs.

本发明优选的,所述GLIPR2在NCBI数据库的ID为152007,在Uniprot数据库的ID为Q5VZR0。Preferably, the GLIPR2 has an ID of 152007 in the NCBI database and an ID of Q5VZR0 in the Uniprot database.

本发明优选的,所述GLIPR2检测试剂指检测GLIPR2在卵巢癌腹膜转移癌组织细胞中的蛋白表达水平的试剂。Preferably, the GLIPR2 detection reagent of the present invention refers to a reagent for detecting the protein expression level of GLIPR2 in cancer tissue cells of peritoneal metastasis of ovarian cancer.

本发明优选的,所述卵巢癌腹膜转移灶癌细胞对铂类药物的耐药性指在新辅助化疗中或非新辅助化疗中卵巢癌腹膜转移灶癌细胞对铂类药物的耐药性。Preferably, in the present invention, the drug resistance of the ovarian cancer peritoneal metastasis cancer cells to platinum drugs refers to the drug resistance of the ovarian cancer peritoneal metastasis cancer cells to platinum drugs during neoadjuvant chemotherapy or non-neoadjuvant chemotherapy.

本发明优选的,所述检测GLIPR2在卵巢癌腹膜转移癌组织细胞中的蛋白表达水平的试剂所采用的原理为基于亲和标记、质谱、色谱或光谱的技术。Preferably, in the present invention, the reagent for detecting the protein expression level of GLIPR2 in ovarian cancer peritoneal metastasis cancer tissue cells adopts a technique based on affinity labeling, mass spectrometry, chromatography or spectroscopy.

本发明优选的,所述检测GLIPR2在卵巢癌腹膜转移癌组织细胞中的蛋白表达水平的试剂所采用的方法为免疫组织化学检测方法。Preferably, in the present invention, the method used by the reagent for detecting the protein expression level of GLIPR2 in ovarian cancer peritoneal metastasis cancer tissue cells is an immunohistochemical detection method.

本发明的有益效果在于:本发明提供了一种基于新标志物GLIPR2的卵巢癌腹膜转移耐药性诊断试剂制备相关的新应用。卵巢癌腹膜转移耐药性诊断尚无有效的标志物,本发明为卵巢癌腹膜转移耐药性诊断方法的开发和未来发展提供了基础。The beneficial effect of the present invention is that the present invention provides a new application related to the preparation of a diagnostic reagent for ovarian cancer peritoneal metastasis drug resistance based on the new marker GLIPR2. There is no effective marker for the diagnosis of ovarian cancer peritoneal metastasis drug resistance, and the present invention provides a basis for the development and future development of a diagnostic method for ovarian cancer peritoneal metastasis drug resistance.

附图说明BRIEF DESCRIPTION OF THE DRAWINGS

为了使本发明的目的、技术方案和有益效果更加清楚,本发明提供如下附图进行说明:In order to make the purpose, technical solution and beneficial effects of the present invention clearer, the present invention provides the following drawings for illustration:

图1为蛋白质组学策略研究卵巢癌腹膜转移耐药性标志物的研究思路;Figure 1 shows the research idea of proteomics strategy to study drug resistance markers of ovarian cancer peritoneal metastasis;

图2为新辅助化疗前后卵巢癌腹膜转移组织的蛋白质图谱差异;Figure 2 shows the difference in protein profiles of peritoneal metastasis tissues of ovarian cancer before and after neoadjuvant chemotherapy;

图3为GLIPR2在新辅助化疗前后卵巢癌腹膜转移组织中的质谱检测相对值。FIG3 shows the relative value of mass spectrometry detection of GLIPR2 in peritoneal metastasis tissue of ovarian cancer before and after neoadjuvant chemotherapy.

图4为GLIPR2在新辅助化疗前后卵巢癌腹膜转移组织中的免疫组化检测值;FIG4 shows the immunohistochemical detection values of GLIPR2 in peritoneal metastasis tissues of ovarian cancer before and after neoadjuvant chemotherapy;

图5为GLIPR2的蛋白表达水平与卵巢癌腹膜转移新辅助化疗敏感性的相关性研究;FIG5 is a study on the correlation between the protein expression level of GLIPR2 and the sensitivity of neoadjuvant chemotherapy for peritoneal metastasis of ovarian cancer;

图6为GLIPR2作为标志物区分新辅助化疗无应答卵巢癌腹膜转移病人的准确性研究。FIG. 6 is a study on the accuracy of GLIPR2 as a marker for distinguishing patients with ovarian cancer peritoneal metastasis who have no response to neoadjuvant chemotherapy.

具体实施方式DETAILED DESCRIPTION

下面结合附图和具体实施例对本发明作进一步说明,以使本领域的技术人员可以更好的理解本发明并能予以实施,但所举实施例不作为对本发明的限定。The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

实施例1、通过蛋白质组学分析策略完成卵巢癌腹膜转移耐药性标志物的发现研究Example 1: Discovery of drug resistance markers for ovarian cancer peritoneal metastasis using proteomic analysis strategy

卵巢癌新辅助化疗或常规化疗的主要药物均为铂类药物,卵巢癌组织内存在异质性,即存在先天化疗敏感细胞,也存在先天化疗耐药细胞,同时先天敏感细胞亦可通过化疗的诱导产生获得性耐药。因此,化疗或新辅助化疗后的残留组织会形成耐药性癌细胞的富集。本研究利用该特点,通过比较卵巢癌腹膜转移新辅助化疗前后的蛋白质图谱筛选卵巢癌腹膜转移耐药性的标志物。具体内容如下:收集新辅助化疗(Neoadjuvantchemotherapy,NACT)前(Pre-NACT)后(Post-NACT)卵巢癌腹膜转移组织各3例,利用TMT蛋白质组学技术检测两种组织中蛋白质组层面的蛋白表达水平,再比较筛选Post-NACT样本中的差异表达蛋白。研究思路如图1所示,两种组织的蛋白质图谱差异如图2所示,其中GLIPR2在Post-NACT样本中的检测信号值显著升高(图3)。The main drugs for neoadjuvant chemotherapy or conventional chemotherapy for ovarian cancer are platinum drugs. There is heterogeneity in ovarian cancer tissues, that is, there are innate chemotherapy-sensitive cells and innate chemotherapy-resistant cells. At the same time, innate sensitive cells can also produce acquired resistance through chemotherapy induction. Therefore, the residual tissue after chemotherapy or neoadjuvant chemotherapy will form an enrichment of resistant cancer cells. This study took advantage of this feature to screen markers of ovarian cancer peritoneal metastasis resistance by comparing the protein profiles before and after neoadjuvant chemotherapy for ovarian cancer peritoneal metastasis. The specific content is as follows: 3 cases of ovarian cancer peritoneal metastasis tissues before (Pre-NACT) and after (Post-NACT) neoadjuvant chemotherapy (Neoadjuvantchemotherapy, NACT) were collected, and the protein expression levels at the proteomic level in the two tissues were detected by TMT proteomics technology, and then the differentially expressed proteins in the Post-NACT samples were compared and screened. The research idea is shown in Figure 1, and the difference in the protein profiles of the two tissues is shown in Figure 2, among which the detection signal value of GLIPR2 in the Post-NACT sample was significantly increased (Figure 3).

本实施例中新辅助化疗前后卵巢癌样本的取材和TMT蛋白质组学技术检测的方法参见Shen Y, Ren Y, Chen K, Cen Y, Zhang B, Lu W, Xu J. The impact ofneoadjuvant chemotherapy on the tumor microenvironment in advanced high-gradeserous carcinoma. Oncogenesis. 2022 Jul 30;11(1):43. doi: 10.1038/s41389-022-00419-1. PMID: 35907904; PMCID: PMC9338965.和McDermott JE, Arshad OA, PetyukVA, Fu Y, Gritsenko MA, Clauss TR, Moore RJ, Schepmoes AA, Zhao R, Monroe ME,Schnaubelt M, Tsai CF, Payne SH, Huang C, Wang LB, Foltz S, Wyczalkowski M,Wu Y, Song E, Brewer MA, Thiagarajan M, Kinsinger CR, Robles AI, Boja ES,Rodriguez H, Chan DW, Zhang B, Zhang Z, Ding L, Smith RD, Liu T, Rodland KD;Clinical Proteomic Tumor Analysis Consortium. Proteogenomic Characterizationof Ovarian HGSC Implicates Mitotic Kinases, Replication Stress in ObservedChromosomal Instability. Cell Rep Med. 2020 Apr 21;1(1):100004. doi: 10.1016/j.xcrm.2020.100004. Epub 2020 Apr 10. Erratum in: Cell Rep Med. 2020 Aug 25;1(5): PMID: 32529193; PMCID: PMC7289043.For the methods of sampling ovarian cancer samples before and after neoadjuvant chemotherapy and detecting them by TMT proteomics technology in this example, please refer to Shen Y, Ren Y, Chen K, Cen Y, Zhang B, Lu W, Xu J. The impact of neoadjuvant chemotherapy on the tumor microenvironment in advanced high-grade serous carcinoma. Oncogenesis. 2022 Jul 30;11(1):43. doi: 10.1038/s41389-022-00419-1. PMID: 35907904; PMCID: PMC9338965. and McDermott JE, Arshad OA, PetyukVA, Fu Y, Gritsenko MA, Clauss TR, Moore RJ, Schepmoes AA, Zhao R, Monroe ME, Schnaubelt M, Tsai CF, Payne SH, Huang C, Wang LB, Foltz S, Wyczalkowski M, Wu Y, Song E, Brewer MA, Thiagarajan M, Kinsinger CR, Robles AI, Boja ES, Rodriguez H, Chan DW, Zhang B, Zhang Z, Ding L, Smith RD, Liu T, Rodland KD; Clinical Proteomic Tumor Analysis Consortium. Proteogenomic Characterization of Ovarian HGSC Implicates Mitotic Kinases, Replication Stress in ObservedChromosomal Instability. Cell Rep Med. 2020 Apr 21;1(1):100004. doi: 10.1016/j.xcrm.2020.100004. Epub 2020 Apr 10. Erratum in: Cell Rep Med. 2020 Aug 25;1(5): PMID: 32529193; PMCID: PMC7289043.

实施例2、GLIPR2在新辅助化疗后卵巢癌腹膜转移组织中表达升高的验证Example 2: Verification of increased expression of GLIPR2 in peritoneal metastasis tissues of ovarian cancer after neoadjuvant chemotherapy

因在发现阶段,各蛋白的检测值仅代表其在3个样本中的平均值,可能存在偶然性。因此,为验证发现阶段发现的GLIPR2的化疗后表达升高的性质,本研究进一步检测了53对新辅助化疗前后的卵巢癌腹膜转移样本,检测方法为临床常用的免疫组织化学技术,结果如图4所示,该实验进一步证明了GLIPR2在新辅助化疗后的蛋白质表达水平升高。因此,GLIPR2具备了作为卵巢癌腹膜转移耐药性标志物的基本性质。Because in the discovery phase, the detection value of each protein only represents its average value in 3 samples, there may be contingency. Therefore, in order to verify the nature of the increased expression of GLIPR2 after chemotherapy found in the discovery phase, this study further detected 53 pairs of ovarian cancer peritoneal metastasis samples before and after neoadjuvant chemotherapy. The detection method is the immunohistochemistry technique commonly used in clinical practice. The results are shown in Figure 4. This experiment further proves that the protein expression level of GLIPR2 increases after neoadjuvant chemotherapy. Therefore, GLIPR2 has the basic properties of being a marker of drug resistance in peritoneal metastasis of ovarian cancer.

本实施例中免疫组织化学操作及结果解读方法参见Fedchenko N, ReifenrathJ. Different approaches for interpretation and reporting ofimmunohistochemistry analysis results in the bone tissue-a review. DiagnPathol. 2014 Nov 29;9:221. doi: 10.1186/s13000-014-0221-9. PMID: 25432701;PMCID: PMC4260254.。For the immunohistochemistry operation and result interpretation method in this example, please refer to Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue-a review. DiagnPathol. 2014 Nov 29;9:221. doi: 10.1186/s13000-014-0221-9. PMID: 25432701;PMCID: PMC4260254.

实施例3、GLIPR2的蛋白表达水平与卵巢癌腹膜转移新辅助化疗敏感性的相关性研究Example 3. Study on the correlation between GLIPR2 protein expression level and sensitivity of neoadjuvant chemotherapy for peritoneal metastasis of ovarian cancer

耐药性诊断最重要的应用之一为在新辅助化疗前诊断先天性耐药性以避免无效的新辅助化疗实施。临床上称为化疗无应答的病人携带的癌细胞多为先天耐药性癌细胞。为研究GLIPR2的表达是否在新辅助化疗无应答(No response)和部分及全部应答(Complete or partial response)两种卵巢癌组织中存在差异,本研究分别收集新辅助化疗前的无应答样本100例和全部或部分应答样本67例。检测GLIPR2在每个样本中的蛋白表达水平,检测方法为临床常用的免疫组织化学方法,数据通过卡法分析,结果发现GLIPR2蛋白表达水平与卵巢癌腹膜转移的新辅助化疗应答程度相关,即与先天耐药性相关(图5)。因此,GLIPR2具备了在新辅助化疗前对先天性或无应答卵巢癌腹膜转移进行诊断的基本性质。One of the most important applications of drug resistance diagnosis is to diagnose innate drug resistance before neoadjuvant chemotherapy to avoid ineffective neoadjuvant chemotherapy. Patients who are clinically known as chemotherapy non-responders carry cancer cells that are mostly innately resistant cancer cells. In order to study whether the expression of GLIPR2 is different in ovarian cancer tissues with no response (No response) and partial or complete response (Complete or partial response) to neoadjuvant chemotherapy, this study collected 100 no response samples and 67 complete or partial response samples before neoadjuvant chemotherapy. The protein expression level of GLIPR2 in each sample was detected by the immunohistochemistry method commonly used in clinical practice. The data were analyzed by the chi-square method. The results showed that the GLIPR2 protein expression level was related to the degree of neoadjuvant chemotherapy response of peritoneal metastasis of ovarian cancer, that is, it was related to innate drug resistance (Figure 5). Therefore, GLIPR2 has the basic properties of diagnosing peritoneal metastasis of innate or non-responsive ovarian cancer before neoadjuvant chemotherapy.

本实施例中新辅助化疗应答情况评价方法参见Ramspott JP, Baert T,MacKintosh ML, Traut A, Ataseven B, Bommert M, Heitz F, Plett H, Schneider S,Waltering KU, Heikaus S, Harter P, du Bois A. Response evaluation afterneoadjuvant therapy: evaluation of chemotherapy response score andserological and/or radiological assessment of response in ovarian cancerpatients. Arch Gynecol Obstet. 2021 Oct;304(4):1021-1032. doi: 10.1007/s00404-021-06020-y. Epub 2021 Mar 4. PMID: 33661392.For the evaluation method of neoadjuvant chemotherapy response in this example, see Ramspott JP, Baert T, MacKintosh ML, Traut A, Ataseven B, Bommert M, Heitz F, Plett H, Schneider S, Waltering KU, Heikaus S, Harter P, du Bois A. Response evaluation afterneoadjuvant therapy: evaluation of chemotherapy response score andserological and/or radiological assessment of response in ovarian cancerpatients. Arch Gynecol Obstet. 2021 Oct;304(4):1021-1032. doi: 10.1007/s00404-021-06020-y. Epub 2021 Mar 4. PMID: 33661392.

实施例4、GLIPR2蛋白表达水平鉴别卵巢癌腹膜转移新辅助化疗耐药性的AUC值Example 4: AUC value of GLIPR2 protein expression level for identifying resistance to neoadjuvant chemotherapy in peritoneal metastasis of ovarian cancer

AUC值是诊断领域公认的衡量标志物准确性的科学方法。为衡量GLIPR2在诊断先天性新辅助化疗耐药性的准确性,本研究通过实施例3的数据绘制了ROC曲线,AUC值为0.8780(图6)。根据数据仍可得出,当阈值定为免疫组化检测GLIPR2在组织中的蛋白表达水平为5时,高于该阈值可判断为新辅助化疗耐药性卵巢癌腹膜转移病人,该判断的灵敏度为82%,特异性为83.58%。综上所述,GLIPR2可作为诊断耐药性卵巢癌腹膜转移的标志物,GLIPR2检测试剂具有制备卵巢癌腹膜转移耐药性诊断试剂的应用。The AUC value is a scientific method recognized in the field of diagnosis to measure the accuracy of markers. In order to measure the accuracy of GLIPR2 in diagnosing congenital neoadjuvant chemotherapy resistance, this study plotted a ROC curve using the data from Example 3, and the AUC value was 0.8780 (Figure 6). According to the data, when the threshold is set at 5 for the protein expression level of GLIPR2 in tissues detected by immunohistochemistry, patients with neoadjuvant chemotherapy-resistant ovarian cancer peritoneal metastasis can be judged as above the threshold, with a sensitivity of 82% and a specificity of 83.58%. In summary, GLIPR2 can be used as a marker for diagnosing peritoneal metastasis of resistant ovarian cancer, and the GLIPR2 detection reagent has the application of preparing a diagnostic reagent for ovarian cancer peritoneal metastasis resistance.

以上所述实施例仅是为充分说明本发明而所举的较佳的实施例,本发明的保护范围不限于此。本技术领域的技术人员在本发明基础上所作的等同替代或变换,均在本发明的保护范围之内。本发明的保护范围以权利要求书为准。The above-described embodiments are only preferred embodiments for fully illustrating the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or changes made by those skilled in the art based on the present invention are within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims (7)

  1. The application of the GLIPR2 detection reagent in preparing a novel auxiliary chemotherapeutic ovarian cancer peritoneal metastasis drug resistance diagnosis reagent is characterized in that: ovarian cancer peritoneal metastasis resistance refers to resistance of primary ovarian cancer peritoneal metastasis cancer cells to platinum drugs.
  2. 2. The use according to claim 1, characterized in that: the ovarian cancer peritoneal metastasis refers to a disease in which primary ovarian cancer metastasizes to the peritoneum forming one or more peritoneal metastasis lesions.
  3. 3. The use according to claim 1, characterized in that: the GLIPR2 has an ID 152007 in the NCBI database and a ID Q5VZR0 in the Uniprot database.
  4. 4. The use according to claim 1, characterized in that: the GLIPR2 detection reagent refers to a reagent for detecting the protein expression level of GLIPR2 in ovarian cancer peritoneal metastasis cancer tissue cells.
  5. 5. The use according to claim 1, characterized in that: the drug resistance of the ovarian cancer peritoneal metastasis cancer cells to the platinum drugs refers to the drug resistance of the ovarian cancer peritoneal metastasis cancer cells to the platinum drugs in the neoadjuvant chemotherapy.
  6. 6. The use according to claim 4, characterized in that: the principle adopted by the reagent for detecting the protein expression level of GLIPR2 in ovarian cancer peritoneal metastasis cancer tissue cells is based on the technology of affinity labeling, mass spectrum, chromatography or spectrum.
  7. 7. The use according to claim 4, characterized in that: the method adopted by the reagent for detecting the protein expression level of GLIPR2 in ovarian cancer peritoneal metastasis cancer tissue cells is an immunohistochemical detection method.
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