Dynamic changes in the urine proteome in two ovarian cancer rat models

Abstract

Ovarian cancer is the most lethal gynecological malignancy in women, and it is likely to metastasize and has a poor prognosis. The early and reliable diagnosis and monitoring of ovarian cancer is very important. Without a homeostasis mechanism, urine can reflect early systemic changes in the body and has a great potential to be used for the early detection of cancer. This study tested whether early changes could be detected in two ovarian cancer rat models. Two rat models were established by either intraperitoneal (i.p.) or orthotopic (o.t.) injection of NuTu-19 ovarian cancer cells in female Fischer344 rats. Urine samples from ovarian cancer rats were collected at five time points during cancer development, and urinary proteins from the rats were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with pre-injection samples, 49 differential proteins that have human orthologues were significantly changed in the orthotopically injected model. Among them, 24 of the differential proteins have previously been reported to be associated with ovarian cancer, six of which were reported to be biomarkers of ovarian cancer. On the 7th day after orthotopic injection, four differential proteins (APOA1, OX2G, CHMP5, HEXB) were identified before obvious metastases appeared. In the intraperitoneal injection model, 76 differential proteins were changed during the course of ovarian cancer development. The results show that urine proteins could enable the early detection and monitoring of ovarian cancer progression and could lay a foundation for further exploration of the biomarkers of ovarian cancer. IntroductionOvarian cancer (OC) is the most lethal gynecological malignancy and it is the fifth leading cause of cancer death in women [1] , mainly because OC can spread to intraperitoneal tissues, such as the omentum in the peritoneal cavity, by the time of diagnosis [2] . The strongest risk factors for this disease are an advanced age and a family history of ovarian cancer. Epithelial ovarian cancer (EOC) is the most common ovarian malignancy and comprises 90% of all ovarian cancers [3] . More than 75% of affected women ovarian carcinomas are not diagnosed until a late stage (stage III or IV) because early-stage disease is not obvious and early symptoms, as well as symptoms of late-stage disease, are nonspecific.Pelvic or abdominal pain, a feeling of pelvic mass and abdominal swelling are the main clinical symptoms, but these are not specific to OC [4] . Currently, women who have symptoms consistent with ovarian cancer usually undergo a physical examination, transvaginal ultrasonography, and measurement of biomarkers such as CA125, but imaging and serum biomarkers tests are of limited 2 value in the early diagnosis of the ovarian carcinomas [5] . The treatment of ovarian cancer usually involves surgery and intraperitoneal and intravenous chemotherapy [6] . At present, patients are typically diagnosed at the advanced stage when the cancer has disseminated within the peritoneal cavity, and comp...

Bioinformatics and Network Pharmacology of the First Crystal Structured Clerodin: Anticancer and Antioxidant Potential against Human Breast Carcinoma Cell

“…By exploring research journals of PubMed, we found a group of seven genes responsible for different forms of cancer, namely, CDK2, 10 HSP90AA1, 11 PIK3CG, 12 FNTA, 13 AR, 14 TP53, 15 and HEXB. 16 We created an interaction network with these seven genes of interest using STRING-DB, an online tool, and used Cytoscape 17 software to figure out the most connected gene. These genes gave the seven target proteins we considered here for docking.…”