Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods

He, Zihao; Duan, Xiaolu; Zeng, Guohua

doi:10.7717/peerj.7872

Cited by 17 publications

(18 citation statements)

References 67 publications

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“…While KLK2 expression in IHC was typically at least weak to moderate in the cytoplasm of normal prostate epithelium, it was reduced or lost in a significant fraction of prostate cancers. This is in line with analyses of published transcriptome data describing lower mRNA expression in prostate cancer than in normal prostatic tissue (reviewed in 11,12 showing associations between low AR signaling and adverse patient outcome 30 and a comparably strong link of reduced expression of the KLK2 regulated PSA to unfavorable prognosis for our prostate cancer cohort. 28 These observations fit with results of Tremblay et al, 10 who also described associations of reduced KLK2 expression with unfavorable prostate cancer phenotype in their 70 cancers.…”

Section: Discussionsupporting

confidence: 89%

“…One study on 70 prostate cancers reported an association between KLK2 downregulation and high tumor grade. 10 Other studies described a reduced KLK2 messenger RNA (mRNA) expression in prostate cancer as compared with normal prostate tissue (reviewed in 11,12 ). To clarify the clinical relevance of KLK2 protein expression in prostate cancer tissue, we took advantage of our pre-existing tissue microarray (TMA) containing more than 12 000 prostate cancer specimens and analyzed KLK2 expression by immunohistochemistry (IHC).…”

Section: Introductionmentioning

confidence: 99%

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Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer

et al. 2020

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Background: Kallikrein-related peptidase 2 (KLK2)-like KLK3 (prostate-specific antigen [PSA])-belongs to the highly conserved serine proteases of the glandular kallikrein protein family (KLK family). Studies suggested that measurement of KLK2 serum levels advanced the predictive accuracy of PSA testing in prostate cancer. Methods: To clarify the potential utility of KLK2 as a prognostic tissue biomarker, KLK2 expression was analyzed by immunohistochemistry in more than 12 000 prostate cancers. Results: Normal epithelium cells usually showed weak to moderate KLK2 immunostaining, whereas KLK2 was negative in 23%, weak in 38%, moderate in 35%, and strong in 4% of 9576 analyzable cancers. Lost or reduced KLK2 immunostaining was associated with advanced tumor stage, high Gleason score, lymph node metastasis, increased cell proliferation, positive resection margin, and early PSA recurrence (P < .0001). Comparison with previously analyzed molecular alterations revealed a strong association of KLK2 loss and presence of TMPRSS2:ERG fusion (P < .0001), most of all analyzed common deletions (9 of 11; P ≤ .03), and decreased PSA immunostaining (P < .0001 each). Cancers with combined negative or weak immunostaining of KLK2 and PSA showed worse prognosis than cancers with at least moderate staining of one or both proteins (P < .0001). Multivariate analyses including established preoperative and postoperative prognostic parameters showed a strong independent prognostic impact of KLK2 loss alone or in combination of PSA, especially in erythroblast transformation-specific-negative cancers (P ≤ .006).

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer

et al. 2020

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“…PCa is a common urologic disorder, affecting the quality of life of aged men. There are numerous epidemiological studies on the relationships between the risk factors and development of PCa [23]. But few studies have focused on the risk factor in local people.…”

Section: Resultsmentioning

confidence: 99%

Profiling of metabolic biomarkers in the serum of prostate cancer patients

Ali¹,

Akram²,

Niaz³

et al. 2020

Ukr.Biochem.J

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Prostate cancer (PCa) is the major cause of the death of men population globally. multiple factors are involved in the initiation and progression of PCa. This study aimed to evaluate different metabolic parameters in the serum of PCa patients. males of 50 years and above age with the recent diagnosis of PCa (digital rectal examination, and elevated serum prostate-specific antigen (PSA) level) were included in the study. Glucose and serum electrolytes level, lactate dehydrogenase activity, parameters of lipid metabolism and liver and kidney functioning were measured on a fully automated analyzer using standard reagent kits. Oxidative stress was evaluated by measuring mdA, CAT, GSH, and SOd in serum. detection of C-reactive protein (CrP), insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF) was performed by immunoassay. It was shown that serum glucose and Hdl levels were lower while total cholesterol, LDL and triglyceride levels were significantly higher in PCa group than in the control group. PCa patients had an elevated level of liver and kidney functional markers. Comparison of the oxidative stress markers in patient and control groups showed significant difference. It was detected that serum levels of CRP, IGF-1 and VEGF were significantly higher in PCa group, compared the control to group (P < 0.05). low level of glucose and dyslipidemia indices in prostate cancer patients indicated metabolic changes and demonstrated the importance of multiple parameters analysis (free PSA, dyslipidemia, VEGF, IGF-1, CrP, and oxidative stress markers) for early PCa diagnostics. k e y w o r d s: prostate cancer, oxidative stress, insulin-like growth factor, vascular endothelial growth factor, c-reactive protein.

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“…Recent developments in bioinformatics and molecular biology have led to high-throughput sequencing (RNA-seq), which can simultaneously measure the expression of many genes [10,11]. Many researchers have used these techniques to characterize the mechanisms of various diseases and to identify potential therapeutic targets [12,13]. Therefore, we will apply the RNA-seq technology and corresponding bioinformatics analysis to identify the molecular mechanisms, biological processes, and potential drug targets in this study.…”

Section: Introductionmentioning

confidence: 99%

Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes

Li³

2020

Preprint

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Background: Rheumatoid arthritis- fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. Methods: The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. Results: In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose- and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3, THOC1, BUB1, and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles.Conclusions: WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA.

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Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods

Cited by 17 publications

References 67 publications

Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer

Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer

Profiling of metabolic biomarkers in the serum of prostate cancer patients

Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes

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