Comparative Proteomics Analysis of Urine Reveals Down-Regulation of Acute Phase Response Signaling and LXR/RXR Activation Pathways in Prostate Cancer

Davalieva, Katarina; Kiprijanovska, Sanja; Kostovska, Ivana Maleva; Stavridis, Sotir; Stankov, Oliver; Komina, Selim; Petruševska, Gordana; Polenakovič, Momir

doi:10.3390/proteomes6010001

Cited by 45 publications

(38 citation statements)

References 61 publications

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“…Previous study suggested that loss of PPARγ may be an important step in the progression of UBC 13. Therefore, its down-regulation in PNO1 KD cells further indicated the role of PNO1 in the migration of UBC.The acute-phase response was the most significantly enriched down-regulated pathway involving the identified DEGs, which is characterized by alteration in the concentrations of a number of plasma proteins produced by the liver, in response to cytokines including IL-1, IL-6, IL-8, TNFα, etc during inflammatory response 16. 14 However, another study reported dramatically increased amplification of PPARγ in UBC tissues, especially those with lymph node metastasis and that PPARγ played an important role in 5673 cell migration and invasion 15.…”

mentioning

confidence: 85%

“…The PCP pathway participates in the regulation of the cytoskeleton. Therefore, its down-regulation in PNO1 KD cells further indicated the role of PNO1 in the migration of UBC.The acute-phase response was the most significantly enriched down-regulated pathway involving the identified DEGs, which is characterized by alteration in the concentrations of a number of plasma proteins produced by the liver, in response to cytokines including IL-1, IL-6, IL-8, TNFα, etc during inflammatory response 16.…”

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confidence: 89%

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Importance of PNO1 for growth and survival of urinary bladder carcinoma: Role in core‐regulatory circuitry

Lin

Yuan

Wang

et al. 2019

J Cellular Molecular Medi

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PNO1 (partner of Nob1) was known as a RNA-binding protein in humans, and its ortholog PNO1 was reported to participate ribosome and proteasome biogenesis inyeasts. Yet there have been few studies about its functions in mammalian cells, and so far its role in human cells has never been reported, especially in urinary bladder cancer (UBC).We interrogated the cellular functions and clinical significance of PNO1 in, and its molecular mechanism through microarrays and bioinformatics analysis.Our findings support that PNO1 participates in promoting proliferation and colonogenesis, while reducing apoptosis of UBC cells, and is also predicted to be associated with the migration and metastasis of UBC PNO1 knockdown (KD) attenuated the tumorigenesis ability of UBC in mouse. PNO1 KD led to the altered expression of 1543 genes that are involved in a number of signalling pathways, biological functions and regulation networks. CD44, PTGS2, cyclin D1, CDK1, IL-8, FRA1, as well as mTOR, p70 S6 kinase, p38 and Caspase-3 proteins were all down-regulated in PNO1 KD cells, suggesting the involvement of PNO1 in inflammatory responses, cell cycle regulation, chemotaxis, cell growth and proliferation, apoptosis, cell migration and invasiveness. This study will enhance our understanding of the molecular mechanism of UBC and may eventually provide novel targets for individualized cancer therapy.

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confidence: 85%

mentioning

confidence: 89%

Importance of PNO1 for growth and survival of urinary bladder carcinoma: Role in core‐regulatory circuitry

Lin

Yuan

Wang

et al. 2019

J Cellular Molecular Medi

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“…These receptors usually exist in biological and pathological pathways related to glucose, lipid homeostasis and the inflammatory response [83]. The proteomic study of urine in prostate cancer patients with a Gleason score of 6.9 ± 1.1 showed that LXR/RXR is activated and the signal of the acute-phase response is significantly downregulated [84]. Clathrin-mediated endocytosis is associated with the migration of prostate cancer cells [85].…”

Section: Rm-1 Prostate Cancer-bearing Micementioning

confidence: 99%

Dynamic changes in the urine proteome of tumor-bearing mouse models of B16 melanoma and RM-1 prostate cancer

Pan

Liu

et al. 2020

Preprint

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Urine can accumulate changes and reflect early physiological and pathological changes of various diseases, such as tumors. Therefore, urine is an ideal source for identification of early biomarkers. In this study, melanoma and prostate cancer-bearing mouse models were established by subcutaneous injection of B16 and RM-1 cells, respectively. Urine samples were collected at four time points during tumor growth. Based on dataindependent acquisition (DIA) technology, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for quantitative analysis. Compared with those before the injection of B16 cells, 38 human homologous differential proteins were identified, and 18 proteins were reported to be related to melanoma. Before the tumor was visible, there were 4 differential proteins, and all were reported to be related to melanoma. Compared with that before the injection of RM-1 cells, a total of 14 human homologous differential proteins were identified, and 9 proteins were reported to be associated with prostate cancer. Before the tumor was palpable, 9 proteins showed significant differences. There were significant differences between the two tumor-bearing models. Through the above experiments and analysis, we found that the urine proteome can reflect the changes in the development and provide early biomarkers of the two tumors and provide clues for the early clinical diagnosis of these diseases.Skin melanoma is one of the most common cancers in the world [1]. Melanoma is produced by the malignant transformation of melanocytes. This disease can occur in any part of the skin and mucous membranes. Melanoma easily metastasizes and is highly invasive and malignant, leading to high mortality. The diagnosis of melanoma is based on a combination of clinical and pathological techniques, including physical examination, histopathological examination and imaging examination. However, due to its variable histological morphology, with little or even no visible pigment, it is difficult to diagnose patients in the early stage and distinguish this condition from benign nevus in the clinic, which makes its early diagnosis difficult [2]. Early treatment of melanoma is mainly surgery, and advanced treatment includes chemotherapy, targeted therapy and immunotherapy. Compared with chemotherapy alone, targeted therapy and immunotherapy have significantly improved the survival rate of patients with advanced melanoma, but these two therapies are usually limited by the drug resistance rate and are not universally applicable [3,4]. The absolute survival rate of patients is still very low [5]. The 5-year survival rates of skin melanoma at stage I to IV are 97% (stage IA), 84% (stage IB), 68%, 55%, and 17% [6]. Therefore, early diagnosis can lead to early treatment and improve the survival rate of patients.Prostate cancer is one of the most common malignant tumors in men. In Europe and America, the incidence rate is highest among those of all cancers in males. The mortality rate is second only to that of lung cancer, ranking second fo...

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“…In the LXR/RXR activation pathway, LXR/RXR is involved in lipid metabolism, including inflammatory responses and cholesterol metabolism [115] . Studies of the comparative proteomic analysis of urine revealed a downregulation of acute-phase response signals and LXR/RXR activation pathways in prostate cancer [127] . Some of the identified pathways were involved in the body's immune response.…”

Section: Nutu-19 Cellsmentioning

confidence: 99%

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

Zhang

Meng

et al. 2019

Preprint

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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...

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Comparative Proteomics Analysis of Urine Reveals Down-Regulation of Acute Phase Response Signaling and LXR/RXR Activation Pathways in Prostate Cancer

Cited by 45 publications

References 61 publications

Importance of PNO1 for growth and survival of urinary bladder carcinoma: Role in core‐regulatory circuitry

Importance of PNO1 for growth and survival of urinary bladder carcinoma: Role in core‐regulatory circuitry

Dynamic changes in the urine proteome of tumor-bearing mouse models of B16 melanoma and RM-1 prostate cancer

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

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