Upregulation of RAD51 expression is associated with progression of thyroid carcinoma

Sarwar, Rizwana; Sheikh, Ahmareen Khalid; Mahjabeen, Ishrat; Bashir, Kashif; Saeed, Soma; Kayani, Mahmood Akhtar

doi:10.1016/j.yexmp.2017.05.001

Cited by 11 publications

(7 citation statements)

References 45 publications

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“…Similar to protein levels, Ki-67 mRNA expression was highest in ATC, and there was a positive correlation between Ki-67 mRNA levels and tumour stage and a negative association between Ki-67 mRNA levels and patient outcomes. Therefore, as has been demonstrated already in the literature [ 72 ], both protein and mRNA levels of Ki-67 allow for a prognostic statement in thyroid carcinomas.…”

Section: Discussionmentioning

confidence: 65%

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Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies

et al. 2022

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Background Papillary and follicular thyroid carcinomas can be treated surgically and with radioiodine therapy, whereas therapeutic options for advanced stage IV medullary and for anaplastic tumours are limited. Recently, somatostatin receptors (SSTs) and the chemokine receptor CXCR4 have been evaluated for the treatment of thyroid carcinomas, however, with contradictory results. Methods The expression of the five SSTs and of CXCR4 was assessed in 90 samples from 56 patients with follicular, papillary, medullary, or anaplastic thyroid carcinoma by means of immunohistochemistry using well-characterised monoclonal antibodies. The stainings were evaluated using the Immunoreactivity Score (IRS) and correlated to clinical data. In order to further substantiate the immunohistochemistry results, in serial sections of a subset of the samples receptor expression was additionally examined at the mRNA level using qRT-PCR. Results Overall, SST and CXCR4 protein expression was low in all four entities. In single cases, however, very high IRS values for SST2 and CXCR4 were observed. SST2 was the most frequently expressed receptor, found in 38% of cases, followed by SST5 and SST4, found in 14 and 9% of tumours, respectively. SST1 and SST3 could not be detected to any significant extent. CXCR4 was present in 12.5% of medullary and 25% of anaplastic carcinomas. Expression SST3, SST4, SST5 and CXCR4 was positively correlated with expression of the proliferation marker Ki-67. Additionally, a negative interrelationship between SST4 or SST5 expression and patient survival and a positive association between SST3 expression and tumour diameter were observed. qRT-PCR revealed a similar receptor expression pattern to that seen at the protein level. However, probably due to the low overall expression, no correlation was found for the SSTs or the CXCR4 between the IRS and the mRNA values. Conclusions SST- or CXCR4-based diagnostics or therapy in thyroid carcinomas should not be considered in general but may be feasible in single cases with high levels of expression of these receptors.

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Section: Discussionmentioning

confidence: 65%

“…Furthermore, in the present study, a positive association between Ki-67 values and tumour stage and a negative correlation between Ki-67 index and patient outcomes was noted. Thus, as already proposed in the literature, Ki-67 may serve as a valuable prognostic marker in thyroid carcinomas [ 16 , 71 , 72 ].…”

Section: Discussionmentioning

confidence: 79%

Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies

et al. 2022

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“…BRCA2 recognizes nuclear lament in single strand DNA loaded with RAD51 during DNA damage and invade the homologous DNA duplex to pair up and initiate homologous recombination repair [12,13]. Although RAD51 expression is tightly regulated in normal cells to avoid aberrant DNA recombination [14], its expression is strongly upregulated in several types of cancer including breast [15][16][17][18]. High levels of RAD51 over-activate homologous recombination, resulting in uncontrolled double-strand breaks repair and cancer cell persistence [19].…”

Section: Introductionmentioning

confidence: 99%

High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer

Patel

Tokumaru

et al. 2022

Breast Cancer Res Treat

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Purpose: Although DNA repair mechanism is a key to prevent carcinogenesis, its activation in established cancer cells may support their proliferation and aggravate cancer progression. RAD51 cooperates with BRCA2 and is essential in the homologous recombination of DNA repair. To this end, we hypothesized that RAD51 gene expression is associated with cancer cell proliferation and poor prognosis of breast cancer (BC) patients.Methods: A total of 8515 primary BC patients with transcriptome and clinical data from 17 independent cohorts were analyzed. Median was used to divide each cohort into high and low RAD51 expression groups.Results: High RAD51 expression enriched DNA repair gene set and was correlated with DNA repair-related genes. Nottingham histological grade, Ki67 expression and cell proliferation-related gene sets (E2F Targets, G2M Checkpoint and Myc Targets) were all signi cantly associated with the high RAD51 BC.RAD51 expression was positively correlated with Homologous Recombination De ciency, as well as both mutation burden and neoantigen that accompanied with higher in ltration of immune cells. Primary BC with lymph node metastases were associated with high expression of RAD51 in 2 cohorts. There was no strong correlation between RAD51 expression and drug sensitivity in cell lines, and RAD51 expression was lower after the neoadjuvant chemotherapy compared to before the treatment. High RAD51 BC was associated with poor prognosis consistently in 3 independent cohorts. Conclusion: RAD51 gene expression is associated with aggressive cancer biology, cancer cell proliferation, and poor survival in breast cancer.

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“…In normal human cells, the expression and activity of RAD51 are tightly controlled in order to avoid aberrant DNA recombination [21]. It is of note that RAD51 expression is strongly increased in breast, thyroid or pancreatic cancer [22][23][24] and that its overexpression is strongly correlated with poor prognosis [25,26]. Over-activated HRR has been proposed to increase the genetic plasticity of cancer cells due to elevated recombination [21,27].…”

Section: Introductionmentioning

confidence: 99%

Regulation of RAD51 at the Transcriptional and Functional Levels: What Prospects for Cancer Therapy?

Orhan

Velázquez

Tabet

et al. 2021

Cancers

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The RAD51 recombinase is a critical effector of Homologous Recombination (HR), which is an essential DNA repair mechanism for double-strand breaks. The RAD51 protein is recruited onto the DNA break by BRCA2 and forms homopolymeric filaments that invade the homologous chromatid and use it as a template for repair. RAD51 filaments are detectable by immunofluorescence as distinct foci in the cell nucleus, and their presence is a read out of HR proficiency. RAD51 is an essential gene, protecting cells from genetic instability. Its expression is low and tightly regulated in normal cells and, contrastingly, elevated in a large fraction of cancers, where its level of expression and activity have been linked with sensitivity to genotoxic treatment. In particular, BRCA-deficient tumors show reduced or obliterated RAD51 foci formation and increased sensitivity to platinum salt or PARP inhibitors. However, resistance to treatment sets in rapidly and is frequently based on a complete or partial restoration of RAD51 foci formation. Consequently, RAD51 could be a highly valuable therapeutic target. Here, we review the multiple levels of regulation that impact the transcription of the RAD51 gene, as well as the post-translational modifications that determine its expression level, recruitment on DNA damage sites and the efficient formation of homofilaments. Some of these regulation levels may be targeted and their impact on cancer cell survival discussed.

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Upregulation of RAD51 expression is associated with progression of thyroid carcinoma

Cited by 11 publications

References 45 publications

Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies

Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies

High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer

Regulation of RAD51 at the Transcriptional and Functional Levels: What Prospects for Cancer Therapy?

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