Study On Clinicopathological Features And Multi-Gene Targeting Sequencing Of Mucinous Ovarian Cancer

Research background:Mucinous Ovarian Cancer(MOC)is a rare subtype of epithelial ovarian cancer and has a poor response to conventional chemotherapy regimens.The early prognosis of the disease is good,but the prognosis of advanced and recurrent patients is extremely poor.At present,patients with different histological types of ovarian cancer basically adopt the same initial treatment plan,and the classification system based on morphological characteristics is limited in guiding treatment and prognosis.Related molecular studies based on Next Generation Sequencing(NGS)have shown that MOC is a heterogeneous disease at the genetic level,and it is expected to improve the prognosis of MOC by analyzing and targeting related genes.Research purposes:To explore the clinicopathological characteristics of MOC and Borderline Mucinous Ovarian Tumor(BMOT),analyze the gene mutation characteristics,mismatch repair defects(dMMR),microsatellite instability(MSI),and tumor mutation burden of the two groups of patients(TMB)and homologous recombination repair defects(HRD),explore the correlation between gene changes and clinicopathological characteristics,and look for potential molecular therapeutic targets.Research method:1.Retrospectively analyze the clinicopathological data of 14 MOC patients(11 primary MOC,3 metastatic MOC)and 11 BMOT patients diagnosed and treated in Shunde Hospital of Southern Medical University from 2016 to 2020,and analyze their clinicopathological characteristics.2.Targeted sequencing of 425 tumor-related genes on two sets of formalin-fixed paraffin-embedded(FFPE)tumor tissue sections,and analyzed genetic information such as gene mutation characteristics,dMMR,MSI,TMB,and HRD scores of the two groups of patients.3.Combine sequencing data with patient clinical data and COSMIC database to explore the correlation between MOC gene changes and patient clinicopathological characteristics,and analyze the mutation characteristics of the two groups of patients.Results:1.The diameter of BMOT tumor is larger than that of primary MOC.The Ki67 proliferation index of primary MOC tumor tissue is higher than that of BMOT.BMOT and primary MOC serum CA125,CA199,CEA,HE4 concentration and tumor tissue CEA,CK7,CK20,CDX2 expressions were not statistically different.2.Analysis of somatic cell sequencing results:81.8%primary MOC,100%metastatic MOC and 90.9%BMOT are accompanied by at least one pathogenic gene mutation.All 3 BRAF mutations were detected in BMOT patients,all of which were rare BRAF mutations,accompanied by KRAS mutations.Seven were detected in BMOT,3 were detected in primary MOC and 7 were detected in metastatic MOC that were not annotated by the COSMIC database as "detrimental" gene mutations.3.Only 1 case of primary MOC detected MSH2 pathogenic mutation.The status of all detected microsatellites is microsatellite stable(MSS).Only 2 cases of MOC had high TMB,and all relapsed after operation.Only 1 case of metastatic MOC detected a pathogenic mutation of BLM,a gene related to the HRR pathway,BRCA1/2 mutations were not detected in BMOT and MOC,and the 3 cases of MOC and 5 cases of BMOT HRD scores were all less than 41 points.4.Analyzing the COSMIC database,the mutation probability of TP53 and BRAF in BMOT is significantly lower than that in MOC.Both groups of tumors have higher frequency mutations in genes such as KRAS,BRAF,CDKN2A,ERBB2,PIK3A,RNF43,among which KRAS,BRAF,ERBB2,and PIK3A are known driver genes for ovarian cancer.5.There was no significant difference between whether the MOC high-frequency mutation genes KRAS and TP53 were mutated or not and the preoperative serum CA125,CA199,HE4 levels,tumor stage,recurrence,and CK7 and CDX2 expression in tumor tissues.Conclusions:1.Ki67 proliferation index in tumor tissue is a useful marker for distinguishing primary MOC and BMOT.2.Draw a map of 425 tumor-related gene mutations in BMOT and MOC.BMOT may respond well to the new RAS/RAF combined inhibitors.BMOT and MOC may not respond well to immune checkpoint inhibitors and PARP inhibitors.3.There may be at least one therapeutic target for 81.8%primary MOC,100%metastatic MOC and 90.9%BMOT.This study identified several potential targets.A small panel containing genes such as KRAS,BRAF,CDKN2A,ERBB2,PIK3A,STK11,RNF43,APC,etc.may be helpful for diagnosis and guiding treatment.