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Tumor-adjacent normal (TAN) tissues, which constitute tumor microenvironment and are different from healthy tissues, provide critical information at molecular levels that can be used to differentiate aggressive tumors from indolent tumors. In this study, we analyzed 52 TAN samples from the Cancer Genome Atlas (TCGA) prostate cancer patients and developed a 10-gene prognostic model that can accurately predict biochemical recurrence-free survival based on the profiles of these genes in TAN tissues. The predictive ability was validated using TAN samples from an independent cohort. These 10 prognostic genes in tumor microenvironment are different from the prognostic genes detected in tumor tissues, indicating distinct progression-related mechanisms in two tissue types. Bioinformatics analysis showed that the prognostic genes in tumor microenvironment were significantly enriched by p53 signaling pathway, which may represent the crosstalk tunnels between tumor and its microenvironment and pathways involving cell-to-cell contact and paracrine/endocrine signaling. The insight acquired by this study has advanced our knowledge of the potential role of tumor microenvironment in prostate cancer progression. [ABSTRACT FROM AUTHOR]

Background: ALDOA plays an essential role in cancer progression in different human cancers; however, its function has not been understood in prostate cancer (PCa). Methods: Associations of ALDOA expression with clinicopathological features and patient prognosis in PCa were evaluated based on data obtained from the Taylor database and our clinical tissue microarray. The potential roles of ALDOA in malignant progression were verified using a series of in vivo and in vitro experiments after stable ALDOA overexpression and knockdown in DU145 and PC3 cell lines. An aldolase A inhibitor was used to determine the effects of inhibition of ALDOA on PCa cell proliferation. Results: Higher expression of ALDOA was positively correlated with the incidence of postoperative metastasis and biochemical recurrence (BCR) and may predict poor prognosis in PCa patients. In vivo experiments demonstrated that overexpression of ALDOA could significantly promote cell proliferation, prolong the cell cycle, and significantly reduce the apoptosis rate of PCa cells. Knockdown of expression of ALDOA could inhibit the proliferation and shorten the cell cycle of PCa cells significantly, with no significant effects on cell apoptosis (P > 0.05). In vitro experiments showed that overexpression of ALDOA could significantly promote tumor growth (P < 0.05), while treatment with the Aldolase A inhibitor naphthol AS-E phosphate dose-dependently suppressed the growth of PCa cells (P < 0.01). The analysis of datasets from the Taylor database showed that there was negative regulatory relationship between the expression of ALDOA and MYPT1 (P < 0.001). Conclusion: Our study revealed that ALDOA played an important role in the progression of PCa. The MYPT1-ALDOA signaling axis may be a new target for the clinical treatment of PCa patients given its negative regulatory relationship. Our study suggests that Aldolase A inhibitors may represent a novel approach to inhibit the growth of PCa. [ABSTRACT FROM AUTHOR]

Transcription factor EB (TFEB), a member of the MiT family, is dysregulated in different cancers and exerts specific biological functions within the tumor microenvironment. Downregulation of TFEB induces macrophage polarization in the TME and promotes tumor progression. However, the biological role and clinical significance of TFEB in prostate cancer (PCa) remain unknown. This study aimed to identify the role of TFEB in PCa and its potential clinical value. We explored TFEB expression in PCa using public databases and verified its prognostic value using immunohistochemistry in PCa tissue samples. The results revealed that TFEB expression was up-regulated in PCa tissues and was associated with cancer metastasis. Next, overexpression of TFEB promoted PCa cell malignant behavior in in vivo and in vitro experiments. RNA-sequencing and bioinformatics analysis showed high expression of TFEB promoted lysosomal biogenesis and knockdown of TFEB expression decreased the number of lysosomes. Furthermore, the ATP-binding cassette transporter A2 (ABCA2) was identified as a target gene of TFEB, which was verified using the cleavage under targets and release using nuclease (CUT&RUN) assay and qRT-PCR. Silencing of ABCA2 reduced lysosomal biogenesis and decreased matrix metalloproteinases expression, which reduced PCa cell invasion and migration in the tumor microenvironment. Our study suggests that TFEB promotes PCa progression by regulating ABCA2 through lysosomal biogenesis and may serve as a prognostic factor or as a potential therapeutic target of PCa. [ABSTRACT FROM AUTHOR]

TFEB, ABCA2, prostate cancer, tumor microenvironment, lysosomal biogenesis, biochemical recurrence, metastasis Keywords: TFEB; ABCA2; prostate cancer; tumor microenvironment; lysosomal biogenesis; biochemical recurrence; metastasis EN TFEB ABCA2 prostate cancer tumor microenvironment lysosomal biogenesis biochemical recurrence metastasis 1 3 3 09/02/21 20210830 NES 210830 In the original article, there was a mistake in B I Figure 6 i b as published. [Extracted from the article]

Abstract: Lymphatic endothelial cells (LECs) originally differentiated from venous endothelial cells express several specific makers that distinguish them from the blood vessels. Lymphangiogenesis, a complex process of sprouting of new lymphatic vessels, is regulated by multiple direct and indirect growth factors. Vascular endothelial growth factor-C (VEGF-C) is the most potent and selective lymphangiogenic factor that plays a crucial role in the establishment of the first lymphatic vessel during embryonic development and in mediating lymphatic metastasis. In addition to VEGF-C, recent studies show that a range of known tumor-produced angiogenic factors also stimulates lymphangiogenesis, suggesting complex and tight regulations of this process. These tumor-derived lymphangiogenic factors may either alone or jointly promote lymphatic metastasis. Understanding regulatory mechanisms of lymphangiogenesis is pivotal for development of lymphangiogenesis antagonists that might therapeutically be used for intervention of lymphatic metastasis. [Copyright &y& Elsevier]

Although dCTP pyrophosphatase 1 (DCTPP1) has been reported to be associated with poor clinical outcomes in various cancers, whether it plays an important role in prostate cancer (PCa) remains unclear. In this study, an immunohistochemical assay showed the protein expression level of DCTPP1 was significantly higher in PCa tissues than in non-cancerous tissues. Moreover, DCTPP1 was upregulated at both protein and mRNA levels in the PCa tissues from high Gleason score patients versus low Gleason score patients. The analysis of The Cancer Genome Atlas RNA-seq data suggested that upregulation of DCTPP1 was inversely correlated with biochemical recurrence free survival and overall survival. The roles of DCTPP1 in tumor progression and autophagy were further validated through cells invasion, migration, apoptosis and proliferation assays in vitro, as well as EMT and autophagy assays in vivo. Advanced bioinformatics analysis identified the evidence supporting the promotional role of DCTPP1 in tumor progression associated with autophagy. We conclude that DCTPP1 may play an important role in PCa progression associated with high autophagy. Overexpression of DCTPP1 may server as a biomarker for predicting poor BCR-free survival and overall survival for PCa patients. [ABSTRACT FROM AUTHOR]

Abstract: Dendritic cells (DCs) have been widely used as cancer vaccines. However, their functional abilities have often been suppressed by tumor-secreted immunosuppressants such as transforming growth factor-beta (TGF-β). We developed a new strategy using a TGF-β insensitive DC as cancer vaccine. The effect of this vaccine was tested in a murine pulmonary metastases model of renal carcinoma (Renca). Tumor lysate-pulsed DCs (TP-DCs) were infected with retrovirus containing gene of dominant negative TGF-β type II receptor (TβRIIDN) and thus made TGF-β insensitive. Vaccination of the mice bearing Renca pulmonary metastases with the TβRIIDN TP-DC induced powerful tumor-specific cytotoxic T lymphocyte (CTL) responses, suppressed pulmonary metastases, and prolonged survival times. These results suggest TGF-β-insensitive TP-DC vaccine can be used to enhance the antitumor efficacy of DC vaccine. [Copyright &y& Elsevier]