The role of WT1 in breast cancer: clinical implications, biological effects and molecular mechanism

Zhang, Ye; Yan, Wei; Yang, Zeyu; Li, Yanling; Tan, Xuanni; Jiang, Jun; Zhang, Yi; Qi, Xiaowei

doi:10.7150/ijbs.39958

Cited by 32 publications

(31 citation statements)

References 57 publications

(77 reference statements)

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“…While functioning as tumor suppresser in lung cancer (49), expression of CLEC3B was proved to be related to a poor prognosis in colorectal cancer and gastric cancer (50,51). WT1 was firstly identified as a tumor suppressor gene in nephroblastoma (52). However, it was demonstrated by subsequent studies that WT1 was related to the disruption of the EMT signaling pathway and docetaxel resistance in breast cancer, high expression of WT1 also corresponded to a lower overall survival (52,53).…”

Section: Discussionmentioning

confidence: 99%

“…WT1 was firstly identified as a tumor suppressor gene in nephroblastoma (52). However, it was demonstrated by subsequent studies that WT1 was related to the disruption of the EMT signaling pathway and docetaxel resistance in breast cancer, high expression of WT1 also corresponded to a lower overall survival (52,53). Functioned as an oncogene, MUC2 was highly expressed in mucin secreting breast cancers and played a pivotal role in regulating cell proliferation, metastasis, and apoptosis (54).…”

Section: Discussionmentioning

confidence: 99%

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Identification and Validation of a Five-Gene Signature Associated With Overall Survival in Breast Cancer Patients

Wang

Chen

et al. 2021

Front. Oncol.

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BackgroundRecent years, the global prevalence of breast cancer (BC) was still high and the underlying molecular mechanisms remained largely unknown. The investigation of prognosis-related biomarkers had become an urgent demand.ResultsIn this study, gene expression profiles and clinical information of breast cancer patients were downloaded from the TCGA database. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1, and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the TCGA entire cohort and an independent external validation cohort. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression.ConclusionsWe established a predictive five-gene signature, which could be helpful for a personalized management in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Five-Gene Signature Associated With Overall Survival in Breast Cancer Patients

Wang

Chen

et al. 2021

Front. Oncol.

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show abstract

“…While functioning as tumor suppresser in lung cancer [50], expression of CLEC3B was proved to be related to poor prognosis in colorectal cancer and gastric cancer [51,52]. WT1 was rstly identi ed as a tumor suppressor gene in nephroblastoma [53]. However, it was demonstrated by subsequent studies that WT1 was related to the disruption of EMT signaling pathway and docetaxel resistance in breast cancer, high expression of WT1 was also corresponding to lower overall survival [53,54].…”

Section: Discussionmentioning

confidence: 99%

“…WT1 was rstly identi ed as a tumor suppressor gene in nephroblastoma [53]. However, it was demonstrated by subsequent studies that WT1 was related to the disruption of EMT signaling pathway and docetaxel resistance in breast cancer, high expression of WT1 was also corresponding to lower overall survival [53,54]. Functioned as an oncogene, MUC2 was highly expressed in mucin secreting breast cancers and played a pivotal role in regulating cell proliferation, metastasis and apoptosis [55].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Five-gene Signature Associated with Overall Survival in Breast Cancer Patients

Wang

Chen

et al. 2020

Preprint

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Background Recent years, attributed to early detection and new therapies, the mortality rates of breast cancer (BC) decreased. Nevertheless, the global prevalence was still high and the underlying molecular mechanisms were remained largely unknown. The investigation of prognosis-related genes as the novel biomarkers for diagnosis and individual treatment had become an urgent demand for clinical practice. Methods Gene expression profiles and clinical information of breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database and randomly divided into training (n = 514) and internal validation (n = 562) cohort by using a random number table. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In the training set, the gene signature was constructed by the least absolute shrinkage and selection operator (LASSO) method based on DEGs screened by R packages. The results were further tested in the internal validation cohort and the entire cohort. Moreover, functions of five genes were explored by MTT, Colony-Formation, scratch and transwell assays. Western blot analysis was used to explore the mechanisms. Results In the training cohort, a total of 2805 protein coding DEGs were acquired through comparing breast cancer tissues (n = 514) with normal tissues (n = 113). A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1 and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the internal validation set and the entire set. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression. Conclusion We established a predictive five-gene signature, which could be helpful for prognosis assessment and personalized management in breast cancer patients.

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“…However, its expression is observed in chronic hepatitis and cirrhotic liver, both of which are associated with HCC. WT1 overexpression is oncogenic 51 and is associated with poor prognosis in breast cancer 52 and leukemia. 53 In addition, a recent report detected the overexpression of the WT-1 factor in 95% of the tumors with worst prognostic analyzed.…”

Section: Common Cancer Antigens In Hccmentioning

confidence: 99%

Peptide-Based Vaccines for Hepatocellular Carcinoma: A Review of Recent Advances

Charneau

Suzuki

Shimomura

et al. 2021

JHC

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Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. After surgery, up to 70% of patients experience relapses. The current first-line therapy for advanced cases of hepatocellular carcinoma (HCC) comprises sorafenib and lenvatinib administered as single-drug therapies. Regorafenib, cabozantinib, and ramucirumab are administered as second-line therapies. Recently, it has been reported that using the immune checkpoint inhibitors atezolizumab (anti-PDL1 antibody) and bevacizumab (anti-VEGF antibody) leads to longer overall survival of unresectable cases, when compared with the use of sorafenib. The role of cancer immunity against HCC has attracted the attention of clinicians. In this review, we describe our phase I/II clinical trials of peptide vaccines targeting GPC3 in HCC and discuss the potential of peptide vaccines targeting common cancer antigens that are highly expressed in HCC, such as WT-I, AFP, ROBO1, and FOXM1. Further, we introduce recent cancer vaccines targeting neoantigens, which have attracted attention in recent times, as well as present our preclinical studies, the results of which might aid to initiate a neoantigen vaccine clinical trial, which would be the first of its kind in Japan.

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The role of WT1 in breast cancer: clinical implications, biological effects and molecular mechanism

Cited by 32 publications

References 57 publications

Identification and Validation of a Five-Gene Signature Associated With Overall Survival in Breast Cancer Patients

Identification and Validation of a Five-Gene Signature Associated With Overall Survival in Breast Cancer Patients

Identification and Validation of a Five-gene Signature Associated with Overall Survival in Breast Cancer Patients

Peptide-Based Vaccines for Hepatocellular Carcinoma: A Review of Recent Advances

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