Upregulation of SPDEF is associated with poor prognosis in prostate cancer

Meiners, Jan; Schulz, Katharina; Möller, Katharina; Höflmayer, Doris; Burdelski, Christoph; Hube‐Magg, Claudia; Simon, Ronald; Göbel, Cosima; Hinsch, Andrea; Reiswich, Viktor; Weidemann, Sören; Izbicki, J. R.; Sauter, Guido; Jacobsen, Frank; Möller‐Koop, Christina; Mandelkow, Tim; Blessin, Niclas C.; Lutz, Florian; Viehweger, Florian; Lennartz, Maximilian; Fraune, Christoph; Heinzer, Hans; Minner, Sarah; Bonk, Sarah; Huland, Hartwig; Graefen, Markus; Schlomm, Thorsten; Büscheck, Franziska

doi:10.3892/ol.2019.10885

Cited by 12 publications

(11 citation statements)

References 43 publications

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Section: Discussionmentioning

confidence: 91%

“…Thus, SPDEF enhances androgen-mediated activation of target genes 33 . Similarly, upregulation of SPDEF expression was seen to be associated with poor prognosis in prostate cancer 43 . These data suggest that upon ligand addition, AR recruits activators that further intensify the transcriptional potential of both type of enhancers namely, bound by AR directly or in trans.…”

Section: Discussionmentioning

confidence: 91%

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A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer

et al. 2020

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Genetic variation at the 8q24 locus is linked with the greater susceptibility to prostate cancer in men of African ancestry. One such African ancestry specific rare variant, rs72725854 (A>G/T) (~6% allele frequency) has been associated with a~2-fold increase in prostate cancer risk. However, the functional relevance of this variant is unknown. Here we show that the variant rs72725854 is present in a prostate cancer-specific enhancer at 8q24 locus. Chromatin-conformation capture and dCas9 mediated enhancer blocking establish a direct regulatory link between this enhancer and lncRNAs PCAT1, PRNCR1 and PVT1. The risk allele ('T') is associated with higher expression of PCAT1, PVT1 and c-myc in prostate tumors. Further, enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. Elevated expression of these lncRNAs and c-myc in risk allele carriers may explain their greater susceptibility to prostate cancer.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 91%

A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer

et al. 2020

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“…SPDEF has a complex correlation with the prognosis of cancer patients. For example, upregulation of SPDEF is associated with poor prognosis in prostate cancer [ 31 ], but it could also serve as a suppressor in colorectal cancer [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of an Epithelial-Mesenchymal Transition-Related Model for Clear Cell Renal Cell Carcinoma Prognosis Prediction

Zhu

et al. 2022

Disease Markers

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Background. A rising amount of data demonstrates that the epithelial-mesenchymal transition (EMT) in clear cell renal cell carcinomas (ccRCC) is connected with the advancement of the cancer. In order to understand the role of EMT in ccRCC, it is critical to integrate molecules involved in EMT into prognosis prediction. The objective of this project was to establish a prognosis prediction model using genes associated with EMT in ccRCC. Methods. We acquired the mRNA expression profiles and clinical information about ccRCC from TCGA database. In this study, we measured differentially expressed EMT-related genes (DEEGs) by two comparison groups (tumor versus normal tissues; “stages I-II” versus “stages III-IV” tumor tissues). Based on classification and regression random forest models, we identified the most important DEEGs in predicting prognosis. Afterwards, a risk-score model was created using the identified important DEEGs. The prediction ability of the risk-score model was calculated by the area under the curve (AUC). A nomogram for prognosis prediction was built using the risk-score in combination with clinical factors. Results. Among the 72 DEEGs, the classification and regression random forest models identified six hub genes (DKK1, DLX4, IL6, KCNN4, RPL22L1, and SPDEF), which exhibited the highest importance values in both models. Through the expression of these six hub genes, a novel risk-score was developed for the prognosis prediction of ccRCC. ROC curves showed the risk-score performed well in both the training (0.749) and testing (0.777) datasets. According to the survival analysis, individuals who were separated into high/low-risk groups had statistically different outcomes in terms of prognosis. Besides, the risk-score model also showed outstanding ability in assessing the progression of ccRCC after treatment. In terms of nomogram, the concordance index (C-index) was 0.79. Additionally, we predicted the differences in response to chemotherapy drugs among patients from low- and high-risk groups. Conclusion. Gene signatures related to EMT could be useful in predicting ccRCC prognosis.

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“…Compared with normal prostate tissue, the expression of SPDEF in prostate cancer is significantly increased. Meanwhile, the increased SPDEF expression is associated with high Gleason grade, advanced stage, rapid cell proliferation, and early prostate cancer recurrence [19]. SPDEF is believed to interact directly with androgen receptors and act as a coactivator of androgen receptors to induce prostate-specific antigen (PSA) expression in prostate tumor cells [3].…”

Section: The Dysregulated Expression Of Spdef In Some Cancersmentioning

confidence: 99%

The role of SPDEF in cancer: promoter or suppressor

Bao¹,

Wang²

2022

neo

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SPDEF, as a member of the ETS transcription factor family, was found to play important roles not only in some normal organs but also in some cancers. Scientists found that the significant increase of SPDEF in some cancers promotes tumor development, while some others found that the expression of SPDEF is lost in some cancers, and the loss of SPDEF is related to the proliferation, invasion, and metastasis. In this review, we summarized the function of SPDEF in normal tissues and its dual behaviors in different cancers, which may become a novel target in the diagnosis and therapy of cancers in the future. Besides, the multi-upstream regulatory mechanism of SPDEF plays different regulatory roles in different tumors, deserving further study. Moreover, there is one research, reporting that SP DEF plays a role in promoting mucus production during viral infection, and this may provide new ideas for future research about virus-associated cancer.

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Upregulation of SPDEF is associated with poor prognosis in prostate cancer

Cited by 12 publications

References 43 publications

A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer

A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer

Construction of an Epithelial-Mesenchymal Transition-Related Model for Clear Cell Renal Cell Carcinoma Prognosis Prediction

The role of SPDEF in cancer: promoter or suppressor

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