Clinical significance of ERG rearrangement subtype and its association with increased p53 expression in Japanese and German prostate cancer

Nishijima, Jun; Hara, Takahito; Ikemoto, Kenzou; A, Oga; Kobayashi, Koji; Kawai, Yuko; Matsumoto, Hisashi; Nagao, Kazuhiro; Sasaki, Kazunori; Gkoleizakis, V; Fichtner, Jan; Matsuyama, Hiroyuki

doi:10.4149/neo_2015_033

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…In the analysis of reviewed articles, there was a consistency between the relationship of ERG protein expression and the biochemical recurrence of PCa ( 38 , 40 , 57 , 61 – 63 ). Hagen et al showed that 13 of 28 patients (46.4%) who had surgical specimens with high ERG levels developed recurrence compared to only 3 (12%) of 25 patients who had tumors with low ERG levels ( p = 0.006) ( 57 ).…”

Section: Resultsmentioning

confidence: 87%

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The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic Evaluation and Treatment of Prostate Cancer: A Systematic Review of the Literature

et al. 2018

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Background: Prostate cancer (PCa) is a heterogeneous disease that lends itself toward numerous therapeutic options depending on its risk stratification. One of the greatest challenges in PCa urologic practice is to select patients who should be referred for biopsy and, for those patients who are diagnosed with cancer, to differentiate between patients with indolent disease from those with an unfavorable prognosis and, to determine ideal patient management and avoid unnecessary interventions. Accordingly, there is a growing body of literature reporting immunohistochemical studies with the objective of determining a prostate cancer prognosis. Among the most frequent biomarkers studied are Ki-67, p53, PTEN, MYC, and ERG. Based on these findings, we systematically reviewed articles that assessed the role of these main prognostic markers in prostate cancer.Methods: Consistent with PRISMA guidelines, we performed a systematic literature search throughout the Web of Science and PubMed Medline databases. We considered all types of studies evaluating the role of Ki-67, p53, PTEN, MYC, and ERG immunohistochemical analysis in prostate cancer until July 2017.Results: We identified 361 articles, 44 of which were summarized in this review. Diagnostically, no single immunohistochemical marker was able to define a tumor as benign or malignant. Prognostically, Ki-67, p53, and MYC were related to the tumor grade given by Gleason score and to the tumor stage (higher levels related to higher tumor grade). Furthermore, Ki-67 was also related to higher PSA levels, shorter disease-free intervals and shorter tumor-specific survival; the latter was also related to p53. The loss of PTEN protein expression showed a higher association with biochemical recurrence and with a worse prognosis, beyond that predicted by the Gleason score and tumor stage. ERG staining also showed a strong association with biochemical recurrence.Conclusion: There are several studies relating immunohistochemical markers with clinical-laboratorial outcomes in prostate cancer, the most frequent being Ki-67, p53, ERG, PTEN, and MYC. However, none of these markers have been validated by literary consensus to be routinely applied in medical practice.

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Section: Resultsmentioning

confidence: 87%

“…Of the selected articles, the analyzed materials in the studies were specimens from prostatectomies (17 studies) ( 25 , 33 , 38 , 40 – 45 , 55 – 59 , 61 – 63 ), TUR (3 studies) ( 33 , 38 , 59 ), biopsies (2 studies) ( 38 , 33 ).…”

Section: Resultsmentioning

confidence: 99%

The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic Evaluation and Treatment of Prostate Cancer: A Systematic Review of the Literature

et al. 2018

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“…Whether TMPRSS2 is involved in various tumors’ pathogenesis via certain molecular mechanisms remains to be elucidated. TMPRSS2 has been found to inhibit colorectal cancer cell migration ( Bowden et al, 2007 ), and its expression was diminished in cases with P53 mutations ( Nishijima et al, 2015 ). In addition, TMPRSS2 was also taken a key part in HCC by driving the recruitment and differentiation of peritumoral fibroblasts into TAMs ( Thunders and Delahunt, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenosides, potential TMPRSS2 inhibitors, a trade-off between the therapeutic combination for anti-PD-1 immunotherapy and the treatment of COVID-19 infection of LUAD patients

et al. 2023

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Background: Acting as a viral entry for coronavirus to invade human cells, TMPRSS2 has become a target for the prevention and treatment of COVID-19 infection. Before this, TMPRSS2 has presented biological functions in cancer, but the roles remain controversial and the mechanism remains unelucidated. Some chemicals have been reported to be inhibitors of TMPRSS2 and also demonstrated other pharmacological properties. At this stage, it is important to discover more new compounds targeting TMPRSS2, especially from natural products, for the prevention and treatment of COVID-19 infection.Methods: We analyzed the correlation between TMPRSS2 expression, methylation level, overall survival rate, clinical parameters, biological process, and determined the correlation between TMPRSS2 and tumor-infiltrating lymphocytes in the tumor and adjacent normal tissue of adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively by using various types of bioinformatics approaches. Moreover, we determined the correlation between TMPRSS2 protein level and the prognosis of LUAD and LUSC cohorts by immunohistochemistry assay. Furthermore, the cancer immunome atlas (TCIA) database was used to predict the relationship between the expression of TMPRSS2 and response to programmed cell death protein 1 (PD-1) blocker immunotherapy in lung cancer patients. Finally, the putative binding site of ginsenosides bound to TMPRSS2 protein was built from homology modeling to screen high-potency TMPRSS2 inhibitors.Results: We found that TMPRSS2 recruits various types of immunocytes, including CD8+, CD4+ T cells, B cells and DCs both in LUAD and LUSC patients, and the correlation between TMPRSS2 expression and CD8+ and CD4+ T cells are stronger in LUAD rather than in LUSC, but excludes macrophages and neutrophils in LUAD patient cohorts. These might be the reason that higher mRNA and protein levels of TMPRSS2 are associated with better prognosis in LUAD cohorts rather than in LUSC cohorts. Furthermore, we found that TMPRSS2 was positively correlated with the prognosis in patient nonresponse to anti-PD-1 therapy. Therefore, we made an inference that increasing the expression level of TMPRSS2 may improve the anti-PD-1 immunotherapy efficacy. Finally, five ginsenosides candidates with high inhibition potency were screened from the natural chemical library to be used as TMPRSS2 inhibitors.Conclusion: All these may imply that TMPRSS2 might be a novel prognostic biomarker and serve as a potential immunomodulator target of immunotherapy combination therapies in LUAD patients nonresponse to anti-PD-1 therapy. Also, these findings may suggest we should pay more attention to LUAD patients, especially those infected with COVID-19, who should avoid medicating TMPRSS2 inhibitors, such as ginsenosides to gain prophylactic and therapeutic benefits against COVID-19.

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“…Prostate cancer PC-3 is a kind of hormone-independent cancer cell [ 20 – 22 ]. This study used a BALB/c nude mouse model inoculated with human PC-3 cells to simulate prostate cancer growth in vivo .…”

Section: Discussionmentioning

confidence: 99%

Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model

Yang

Zhao

et al. 2015

Med Sci Monit

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BackgroundCnidium lactone is a natural coumarin compound that can inhibit a variety of cancer cell proliferation and induce cancer cell apoptosis. This experiment investigated the effect of cnidium lactone on molecular marker expression in prostate cancer nude mice to study its effect in inducing apoptosis.Material/MethodsWe randomly and equally divided 30 male BALB/C nude mice inoculated with human prostate cancer cells PC-3 into a negative control group, a cyclophosphamide group (500 mg/Kg), and cnidium lactone groups at 3 doses (280 mg/Kg, 140 mg/Kg, and 70 mg/Kg). The mice were weighed at 2 weeks after administration. Tunnel assay was applied to test the nude mice tumor cell apoptosis. ELISA was performed to detect serum AMACR, CD147, mutant P53, BCL-2, AND BAX expression levels. Tumor tissue was separated and weighed.ResultsMice weight did not change significantly in the groups receiving 3 different doses of cnidium lactone(p>0.05), while it decreased obviously in the cyclophosphamide group (p<0.05). Tumor weight, CD147, mutant P53, and BCL-2 levels were significantly lower in the groups receiving 3 different doses of cnidium lactone than in the negative control group (p<0.05). Among them, the abovementioned indexes decreased markedly in the 280 mg/Kg and 140 mg/Kg dose groups than in the cyclophosphamide group (p<0.05). AMACR and BAX levels showed no significant difference in the cnidium lactone group or the cyclophosphamide group (p>0.05).ConclusionsCnidium lactone may induce prostate cancer cell apoptosis and inhibit its proliferation through regulating CD147, mutant P53, and BCL-2 expression in nude mice.

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Clinical significance of ERG rearrangement subtype and its association with increased p53 expression in Japanese and German prostate cancer

Abstract: ERG, p53, prostate cancer, TMPRSS2-ERG fusion.

Cited by 8 publications

References 37 publications

The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic Evaluation and Treatment of Prostate Cancer: A Systematic Review of the Literature

The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic Evaluation and Treatment of Prostate Cancer: A Systematic Review of the Literature

Ginsenosides, potential TMPRSS2 inhibitors, a trade-off between the therapeutic combination for anti-PD-1 immunotherapy and the treatment of COVID-19 infection of LUAD patients

Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model

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