Expression And Significance Of IGFL1 In Serous Ovarian Carcinoma

Among all gynecological diseases,ovarian cancer is a disease with poor prognosis and high mortality.It is more likely to occur in middle-aged and elderly women,and its incidence ranks the third,next only to cervical cancer and endometrial cancer.There are many histologic types of ovarian cancer,of which epithelial ovarian cancer is the most common.In epithelial ovarian cancer,serous carcinoma accounts for approximately 75% of ovarian cancer and is the most common diagnosis.Early stage(stage I and II)ovarian cancer has no typical clinical symptoms,and due to the limitations of early screening techniques,most patients are already advanced by the time they are diagnosed(stage III or IV).The overall survival rate for advanced ovarian cancer is only 29%,and the prognosis is poor.Age,histological type,tumor tissue size,FIGO stage,lymph node metastasis are independent prognostic factors of ovarian cancer.To explore new prognostic biomarkers for serous ovarian carcinoma,we downloaded data about serous ovarian carcinoma from The Cancer Genome Atlas(TCGA)database and screened for differentially expressed genes(DEGs)by volcano map and Venn analysis.Finally,IGFL1 gene was selected as the target gene related to the prognosis of patients with serous ovarian carcinoma.The IGFL(insulin-like growth factor)gene cluster consists of four expressed genes and two pseudogenes,and its expression pattern is similar to that of IGF(insulin-like growth factor).It has been shown that IGFL is expressed in fetal tissue,breast,prostate and many other cancers,and has been confirmed by qRT-PCR that IGFL1 m RNA is expressed in ovary and spinal cord,but the expression and significance of IGFL1 in serous ovarian carcinoma tissue remains unclear.ObjectiveIn this study,qRT-PCR and immunohistochemistry SP were used to detect the m RNA expression and protein positive expression rate of IGFL1 in different ovarian tissues,and to analyze the significance and effect of IGFL1 in serous ovarian carcinoma tissues,so as to provide the basis for IGFL1 as a new prognostic factor.Materials and methods1.subjects:A total of 66 patients were collected.All patients underwent surgical resection of ovarian tissue in the Third Affiliated Hospital of Zhengzhou University from September 2013 to March 2015,including 30 patients with benign serous ovarian tumor(benign group)and 36 patients with serous ovarian carcinoma(malignant group).None of the patients had a history of other tumors or spinal cord related diseases.They did not receive radiotherapy,chemotherapy or drug therapy before surgery,and were confirmed by pathology after surgery.The specimens were collected with informed consent of the patients and approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University.Due to restrictions of ethical review,no normal ovarian tissue was collected.2.Methods(1)The gene expression profile and clinical information of serous ovarian carcinoma were downloaded from The Cancer Genome Atlas(TCGA)database,and the differentially expressed genes(DEGs)were screened by bioinformatics technology.The relationship between DEGs and prognosis of patients with serous ovarian carcinoma was analyzed,and IGFL1 was finally determined as The differentially expressed gene.(2)Immunohistochemistry SP method and qRT-PCR were used to detect the expression of IGFL1 gene in benign serous ovarian tumor and serous ovarian carcinoma.3.Statistical methodsSPSS26.0 was used for statistical analysis in this study.x±s was used to represent the normal distribution measurement data,and percentage(%)was used to represent the enumeration data.The chi-square test and Fisher’s exact chi-square test were used to compare the clinicopathological parameters.Kaplan-Meier analysis was used for survival analysis.Logistic regression model was established to analyze the prognostic factors of serous ovarian carcinoma.When P < 0.05 think difference was statistically significant.Results1.The relevant data information was downloaded from TCGA database,and bioinformatics method was used to explore and determine the correlation between IGFL1 and prognosis of patients with serous ovarian carcinoma.GO and KEGG analysis showed that IGFL1 was closely related to cell growth,metabolism,apoptosis and immune system regulation.2.The qRT-PCR results confirmed that the relative expression level of IGFL1 m RNA in benign and malignant groups was statistically significant(P=0.002).The expression of IGFL1 m RNA in serous carcinoma was closely related to age,FIGO stage,and histological type of samples.In Logistic regression model,univariate analysis showed that IGFL1 overexpression,patient age,FIGO stage,and histological type were strongly associated with the progression of serous ovarian carcinoma.Multivariate analysis showed that high expression of IGFL1 m RNA and histological type were independent predictors of progression of serous ovarian carcinoma.Kaplan-Meier survival analysis results show that higher IGFL1 express the worse prognosis(P < 0.05).3.The immunohistochemical SP results confirmed that the positive expression rate of IGFL1 protein in benign and malignant groups were 56.67%(17/30)and80.56%(29/36),respectively,with statistical significance(P = 0.001).The positive expression of IGFL1 protein was localized in the cytoplasm,and it was distributed as brown-yellow granules under the microscope.Unilateral and bilateral tumor involvement appendages and FIGO stage were associated with differences in IGFL1 positive expression rates,with higher positive expression rates in patients with bilateral tumor involvement appendages and in advanced cases.Conclusions1.The differential gene IGFL1 was screened from TCGA database,which may affect the development of serous ovarian cancer by regulating cell growth,metabolism,apoptosis and immune system.2.The results of clinical specimen verification showed that IGFL1 was highly expressed in serous ovarian carcinoma tissues,and the high expression of IGFL1 was closely associated with poor prognosis in patients with serous ovarian carcinoma.IGFL1 may be a new prognostic factor for serous ovarian carcinoma.