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Background: Adrenocortical carcinoma (ACC) represents the rare urological epithelial cancer of urinary tract, which has a large mass and is usually diagnosed at the advanced stage, thus inducing the poor prognosis. As a result, early detection and diagnosis are more important for the prognosis rather than the treatment of ACC. There is evidence supporting the association of Sulfatase2 (SULF2) with bladder cancer. However, the relationships of SULF2 with the clinical features and immune infiltration of ACC remain unclear. Methods: This work comprehensively investigated the different expression levels of SULF2 within ACC and its prognostic significance through various databases including Gene Expression Profiling Interaction Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Kaplan-Meier (KM) plotter and UALCAN. Besides, SULF2 levels within different tumor and paraneoplastic tissues were examined based on Human Protein Atlas (HPA) and TIMER. Afterwards, this study identified differentially expressed genes (DEGs) in high-compared with low-SULF2-expression groups. To predict the possible interaction between SULF2 and its targets, a protein-protein interaction (PPI) network was constructed based on relevant data collected in STRING database. Besides, the SULF2 functional annotation was carried out, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA. In addition, gene mutation analysis was also performed based on the cBioPortal database. The relation of SULF2 with immune infiltration was analyzed from various aspects by using the resources of various databases including TIMER, TISIDB, and GEPIA, which was first reported in this work. Finally, R package was utilized to plot the receiver operating characteristic (ROC) curves of diagnosis, time-dependent survival, and the association of SULF2 with cancer stage and the nomogram model. Finally, CellMiner dataset was adopted for SULF2 correlation as well as drug sensitivity analysis. Results: Relative to healthy people, SULF2 level markedly elevated within ACC tissues. Besides, SULF2 up-regulation significantly predicted the dismal prognostic outcome, which may be an important prognostic factor. Afterwards, the PPI network was constructed, and the possible link of SULF2 with the corresponding targets was predicted. Besides, up-regulated SULF2 expression was tightly related to immune regulation and tumor-infiltration immune cell (TIICs), including CD8+, CD4+ and mast cells. Finally, SULF2 expression was speculated to help determine the sensitivity of certain drugs. Conclusions: SULF2 may offer a new therapeutic target for ACC patients and become an important potential prognostic biomarker.
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Objective: To evaluate the effectiveness and safety of transurethral resection of the prostate (TURP), holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) in the treatment of benign prostatic hyperplasia using a network Meta-analysis. Methods: Randomized controlled trials of TURP, HoLEP and ThuLEP for benign prostatic hyperplasia were collected by computerized searches of databases including CNKI, WANFANG, VIP, PubMed, The Cochrane Library, the Web of Science and Embase, with a search time frame of build to January 2022. The literature was screened and data was extracted by two investigators separately, while the risk of bias of the included studies was evaluated before systematic evaluation and network meta-analysis using ADDIS 1.16.8 software and RevMan 5.3 software. Results: A total of 27 RCTs with a total of 3335 patients were involved. The results of the network meta-analysis showed that ThuLEP was better than the remaining two procedures in terms of enhancing patients' subjective perception and improving objective indicators, and the incidence of adverse events such as postoperative urethral stricture and urinary incontinence was lower compared with that of conventional TURP in both short- and long-term postoperative follow-ups. Conclusion: As ThuLEP is effective, safe, and featured with few postoperative complications, it can be the preferred surgical procedure for prostate enlargement. Nevertheless, because of the limited number of studies included, more-sample, multicenter, double-blind clinical randomized controlled trials are required in the future to further verify the findings of the present study.
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Alterations in tryptophan (Trp) metabolism facilitate the continuous modulation of tumor progression, including tumor growth, distant metastasis, and chemoresistance development. Although there is a high correlation between Trp metabolism and tumor progression, it is unknown whether and how Trp metabolism affects the development of prostate cancer. In this study, we reported that the overexpression of Trp hydroxylase 1 (TPH1) caused the upregulation of Trp hydroxylation and mediated the production of 5-hydroxytryptamine (5-HT), contributing to tumor growth and poor prognosis in patients with prostate cancer. An increase in 5-HT levels triggered the activation of the Axin 1/ß-catenin signaling pathway, thus enhancing cell proliferation and migration. Consequently, ß-catenin cooperated with the Krüppel-type zinc finger family transcription factor ZBP-89 to upregulate TPH1 expression, further promoting Trp hydroxylation and forming the TPH1/5-HT/ß-catenin/ZBP-89/THP1 positive feedback signaling loop. Interruption of the signaling loop by the THP1 inhibitor 4-chloro-dl-phenylalanine (PCPA) significantly improved anticancer effects and suppressed lung metastasis in prostate cancer-bearing mice. Our findings revealed a mechanism by which TPH1 promotes prostate cancer growth by inducing Trp hydroxylation and identified a novel THP1 target for an innovative prostate cancer therapeutic strategy.