Expression of ERBB Family Members as Predictive Markers of Prostate Cancer Progression and Mortality

Background: EGFR, ERBB2, ERBB3, and ERBB4 are growth receptors of the ERBB family implicated in the development of epithelial cancers. Studies have suggested a role for EGFR and ERBB3 in the development of prostate cancer (PC), while the involvement of ERBB2 and ERBB4 remains unclear. In this study, we evaluated the expression of all members of the ERBB family in PC tissue from a large cohort and determined their contribution, alone or in combination, as prognostic markers. Methods: Using immunofluorescence coupled with digital image analyses, we quantified the expression of EGFR, ERBB2, ERBB3, and ERBB4 on radical prostatectomy specimens (n = 285) arrayed on six tissue microarrays. By combining EGFR, ERBB2, and ERBB3 protein expression in a decision tree model, we identified an association with biochemical recurrence (log rank = 25.295, p < 0.001), development of bone metastases (log rank = 23.228, p < 0.001), and cancer-specific mortality (log rank = 24.586, p < 0.001). Conclusions: Our study revealed that specific protein expression patterns of ERBB family members are associated with an increased risk of PC progression and mortality.

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SPINK1 Protein Expression and Prostate Cancer Progression

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-13-1341 ◽

2014 ◽

Vol 20 (18) ◽

pp. 4904-4911 ◽

Cited By ~ 46

Author(s):

Richard Flavin ◽

Andreas Pettersson ◽

Whitney K. Hendrickson ◽

Michelangelo Fiorentino ◽

Stephen Finn ◽

...

Keyword(s):

Prostate Cancer ◽

Protein Expression ◽

Cancer Progression ◽

Prostate Cancer Progression

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Phylogenetic Comparison and Splicing Analysis of the U1 snRNP-specific Protein U1C in Eukaryotes

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.696319 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kai-Lu Zhang ◽

Jian-Li Zhou ◽

Jing-Fang Yang ◽

Yu-Zhen Zhao ◽

Debatosh Das ◽

...

Keyword(s):

Gene Family ◽

Cancer Progression ◽

Expression Profiles ◽

Expression Patterns ◽

Specific Protein ◽

Comprehensive Overview ◽

Small Nuclear Ribonucleoprotein ◽

U1 Snrnp ◽

Multiple Copies ◽

And Function

As a pivotal regulator of 5’ splice site recognition, U1 small nuclear ribonucleoprotein (U1 snRNP)-specific protein C (U1C) regulates pre-mRNA splicing by interacting with other components of the U1 snRNP complex. Previous studies have shown that U1 snRNP and its components are linked to a variety of diseases, including cancer. However, the phylogenetic relationships and expression profiles of U1C have not been studied systematically. To this end, we identified a total of 110 animal U1C genes and compared them to homologues from yeast and plants. Bioinformatics analysis shows that the structure and function of U1C proteins is relatively conserved and is found in multiple copies in a few members of the U1C gene family. Furthermore, the expression patterns reveal that U1Cs have potential roles in cancer progression and human development. In summary, our study presents a comprehensive overview of the animal U1C gene family, which can provide fundamental data and potential cues for further research in deciphering the molecular function of this splicing regulator.

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Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway

Molecules ◽

10.3390/molecules25204619 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4619

Author(s):

Eun Yeong Lim ◽

Joon Park ◽

Yun Tai Kim ◽

Min Jung Kim

Keyword(s):

Prostate Cancer ◽

Protein Expression ◽

Signaling Pathway ◽

Cancer Progression ◽

Migration And Invasion ◽

Dependent Manner ◽

Castration Resistant Prostate Cancer ◽

Monocyte Chemoattractant Protein 1 ◽

Downstream Signaling ◽

Castration Resistant

Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat chronic psychiatric disorders, including depression and neuropathic pain. IMI also has inhibitory effects against various cancer types, including prostate cancer; however, the mechanism of its anticancer activity is not well understood. In the present study, we investigated the antimetastatic and anti-invasive effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear factor kappa B (NF-κB) signaling pathway. While IMI did not induce cell death, it attenuated PC-3 cell proliferation. According to the wound healing assay and invasion assay, migration and invasion in PC-3 cells were significantly inhibited by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 protein expression levels. Furthermore, IMI treatment resulted in decreased AKT-mediated downstream signaling, including p-inhibitor of κB kinase (IKK)α/β, p-inhibitor of κB (IκBα), and p-p65. Inhibited NF-κB signaling reduced the secretion of several proinflammatory cytokines and chemokine by PC-3 cells. Overall, our study explored the negative correlation between the use of antidepressants and prostate cancer progression, showing that IMI attenuated cell viability, migration, and invasion of PC-3 cells by suppressing the expression of AKT and NF-κB-related signaling proteins and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1).

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Expression of MTDH and IL-10 Is an Independent Predictor of Worse Prognosis in ER-Negative or PR-Negative Breast Cancer Patients

Journal of Clinical Medicine ◽

10.3390/jcm9103153 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3153

Author(s):

Pei-Yi Chu ◽

Shin-Mae Wang ◽

Po-Ming Chen ◽

Feng-Yao Tang ◽

En-Pei Isabel Chiang

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Mrna Expression ◽

Cancer Patients ◽

Expression Patterns ◽

Hypoxia Inducible Factor ◽

Tumor Hypoxia ◽

Tissue Microarrays ◽

Breast Cancer Patients ◽

Worse Prognosis

(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy.

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08-02 Identifying Disease-specific Protein Expression Patterns Within the Syndrome of Schizophrenia

Acta Neuropsychiatrica ◽

10.1017/s0924270800032300 ◽

2006 ◽

Vol 18 (6) ◽

pp. 331-332

Author(s):

B Dean

Keyword(s):

Protein Expression ◽

Expression Patterns ◽

Specific Protein ◽

Disease Specific

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HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters

Disease Markers ◽

10.1155/2019/6315936 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 2

Author(s):

Marta Smolińska ◽

Dariusz Grzanka ◽

Paulina Antosik ◽

Anna Kasperska ◽

Izabela Neska-Długosz ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Statistical Significance ◽

Expression Patterns ◽

Clinical Information ◽

Tissue Microarrays ◽

Gastric Cancer Tissue ◽

Cancer Tissue ◽

Satb1 Expression

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.

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Construction of tissue microarrays using pre-existing slides as source of tissue when paraffin blocks are unavailable

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-201171 ◽

2013 ◽

Vol 66 (7) ◽

pp. 627-629 ◽

Cited By ~ 3

Author(s):

Fang-Ming Deng ◽

Yan Zhao ◽

Xiantian Kong ◽

Peng Lee ◽

Jonathan Melamed

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Tissue Microarray ◽

Expression Patterns ◽

Tissue Microarrays ◽

Viable Alternative ◽

Slide Material ◽

Intermediate Density

AimTo develop and validate a technique for construction of intermediate density tissue microarray (TMA) slides based on the transfer of tissue from pre-existing routine slides provided for pathology diagnosis with validation to show preservation of morphology and antigenicity of the transferred tissue.MethodsProstate cancer patch TMAs were constructed using 20 cores acquired from radical prostatectomy histology slides. The preservation of morphology and antigenicity of these patch TMAs were tested with immunohistochemistry (IHC) in comparison to a traditional TMA.ResultsAfter IHC staining, 35 of 39 cores (89.7%) on the patch TMA were intact compared with 39 of 40 cores (97.5%) on the traditional TMA. Expression patterns and density of the antigens (34BE12, p63 and AMACR) on the patch TMA were almost identical to the traditional TMA.ConclusionsPatch TMA represents a viable alternative for tissue-based IHC studies when paraffin blocks are unavailable. This may be a valuable tool for allowing use of archival slide material for IHC and enable a standardized TMA platform to be used when the slides sent for review from other institutions are the only source of tissue available.

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The Combined Percentage of Gleason Patterns 4 and 5 Is the Best Predictor of Cancer Progression After Radical Prostatectomy

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.018 ◽

2005 ◽

Vol 23 (13) ◽

pp. 2911-2917 ◽

Cited By ~ 75

Author(s):

Liang Cheng ◽

Michael O. Koch ◽

Beth E. Juliar ◽

Joanne K. Daggy ◽

Richard S. Foster ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Cancer Patients ◽

Gleason Score ◽

Cancer Progression ◽

Tumor Volume ◽

High Grade ◽

Cox Regression Analysis ◽

Total Tumor Volume ◽

Increased Risk

Purpose Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. Patients and Methods Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. Results A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. Conclusion The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.

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PUM1 represses CDKN1B translation and contributes to prostate cancer progression

10.1101/2021.05.27.21257930 ◽

2021 ◽

Author(s):

Eugene Yujun Xu

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Protein Expression ◽

Cancer Cell ◽

Cancer Progression ◽

Translational Control ◽

Rna Binding ◽

Prostate Cancer Cell ◽

Mrna Level ◽

Critical Role

Posttranscriptional regulation of cancer gene expression programs plays a vital role in carcinogenesis; identifying the critical regulators of tumorigenesis and their molecular targets may provide novel strategies for cancer diagnosis and therapeutics. Highly conserved RNA binding protein PUM1 regulates mouse growth and cell proliferation, propelling us to examine its role in cancer. We found human PUM1 is highly expressed in a diverse group of cancer, including prostate cancer; enhanced PUM1 expression is also correlated with reduced survival among prostate cancer patients. Detailed expression analysis in twenty prostate cancer tissues showed enhanced expression of PUM1 at mRNA and protein levels. Knockdown of PUM1 reduced prostate cancer cell proliferation and colony formation, and subcutaneous injection of PUM1 knockdown cells led to reduced tumor size. Downregulation of PUM1 in prostate cancer cells consistently elevated CDKN1B protein expression through increased translation but did not impact its mRNA level, while overexpression of PUM1 reduced CDKN1B protein level. Our finding established a critical role of PUM1 mediated translational control, particularly the PUM1-CDKN1B axis, in prostate cancer cell growth and tumorigenesis. We proposed that PUM1-CDKN1B regulatory axis may represent a novel mechanism for the loss of CDKN1B protein expression in diverse cancers and could be potential targets for therapeutics development.

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Gene Expression Alterations during Development of Castration-Resistant Prostate Cancer Are Detected in Circulating Tumor Cells

Cancers ◽

10.3390/cancers12010039 ◽

2019 ◽

Vol 12 (1) ◽

pp. 39 ◽

Cited By ~ 2

Author(s):

Andreas Josefsson ◽

Karin Larsson ◽

Eva Freyhult ◽

Jan-Erik Damber ◽

Karin Welén

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Progression ◽

Expression Patterns ◽

Therapy Resistance ◽

Castration Resistant Prostate Cancer ◽

Cancer Specific Survival ◽

Castration Resistant

Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC.

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