Assessing the prognostic value of stemness-related genes in breast cancer patients

Wang, Wenjie; Wang, Han; Wang, Meng-Sen; Huang, Yongzhen; Ma, Yuan; Qi, Jie; Shi, Jianping; Li, Wei

doi:10.1038/s41598-020-73164-3

Cited by 6 publications

(7 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous study suggested that GRB7 overexpression was an independent factor of poor prognosis ( 34 ). Furthermore, we observed several arm-level deletions of BC tumor suppressor genes and favorable BC prognostic genes in patients who failed to achieve pCR, including CDKN2C ( 35 ), EPS15 ( 36 ), etc. Of note, there were a considerable number of genes related to BC development and progression in the regions where deletions were identified, including CDKN2C , EPS15 , CBL , etc.…”

Section: Discussionmentioning

confidence: 95%

Baseline Mutations and Up-Regulation of PI3K-AKT Pathway Serve as Potential Indicators of Lack of Response to Neoadjuvant Chemotherapy in Stage II/III Breast Cancer

et al. 2022

View full text Add to dashboard Cite

BackgroundNeoadjuvant chemotherapy (NAC) has been expanded to hormone receptor (HR) positive breast cancer (BC) patients with operable disease, to increase the likelihood of breast-conserving surgery. Genomic profiling at baseline would reveal NAC response relevant genomic features and signaling pathways, guiding clinical NAC utilization based on patients’ genomic characteristics.MethodsWe prospectively studied stage II/III BC patients who were eligible for breast-conserving surgery. Patients received epirubicin and cyclophosphamide for 4 cycles, followed by another 4-cycle docetaxel, and human epidermal growth factor receptor (HER2) positive patients were additionally treated with herceptin when using docetaxel (EC-T(H)). NAC responses were evaluated as pathologic complete response (pCR) or non-pathologic complete response (non-pCR). Genomic features related to NAC responses were identified by profiling baseline tumor tissues sampled one day before NAC, using whole-exome sequencing. Differentially expressed genes and up-/down-regulated pathways were investigated by performing RNA-sequencing.ResultsA total of 25 stage II/III BC patients were enrolled, including 5 patients ultimately evaluated as pCR and 20 patients evaluated as non-pCR. PIK3CA (48%) and TP53 (40%) mutations were enriched in patients not achieving pCR. Mutated phosphatidylinositol-3-kinase-AKT (PI3K-AKT) pathway and homologous recombinational repair pathway were also more frequently observed in patients evaluated as non-pCR. Significant arm-level amplifications (8q24.23 and 17q12) and deletions (1p32.2, 4p14, 7q11.23, 10q21.3, 11q23.3, etc.) were identified among patients not achieving pCR, while patients achieving pCR displayed no significant copy number alterations. Significantly up-regulated expression of PI3K-AKT pathway genes was also detected among patients failed to achieve pCR, compared to patients achieving pCR.ConclusionCompared to BC patients achieving pCR to NAC, aberrant activation of PI3K-AKT pathway genes were more frequently observed in patients not achieving pCR, consistent with the significant up-regulation of PI3K-AKT pathway gene expression in the non-pCR subgroup. Together, these findings indicate that upregulated PI3K-AKT pathway serves as a potential indicator of lack of response to NAC in stage II/III BC patients, and other effective therapeutic options are urgently needed for those resistant patients.

show abstract

Section: Discussionmentioning

confidence: 95%

Baseline Mutations and Up-Regulation of PI3K-AKT Pathway Serve as Potential Indicators of Lack of Response to Neoadjuvant Chemotherapy in Stage II/III Breast Cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Xu et al also established an NPR3-containing 7-IRG risk model, and the risk score presented excellent predictive ability in gastric cancer and revealed the status of the tumour immune microenvironment 32 . Similarly, Wang et al proposed a model consisting of 4 stemness-related genes (PSMB9, CXCL13, NPR3, and CDKN2C) to identify targets of BC stem cells and improved the therapeutic effect 33 . In our study, NPR3 with the other 6 IRGs constituted an excellent model with excellent prognostic and TME-predictive value for BC.…”

Section: Discussionmentioning

confidence: 99%

A novel immune score model predicting the prognosis and immunotherapy response of breast cancer

Wang

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Breast cancer (BC) is one of the most common malignancies. However, the existing pathological grading system cannot accurately and effectively predict the survival rate and immune checkpoint treatment response of BC patients. In this study, based on The Cancer Genome Atlas (TCGA) database, a total of 7 immune-related genes (IRGs) were screened out to construct a prognostic model. Subsequently, the clinical prognosis, pathological characteristics, cancer-immunity cycle, tumour immune dysfunction and exclusion (TIDE) score, and immune checkpoint inhibitor (ICI) response were compared between the high- and low-risk groups. In addition, we determined the potential regulatory effect of NPR3 on BC cell proliferation, migration, and apoptosis. The model consisting of 7 IRGs was an independent prognostic factor. Patients with lower risk scores exhibited longer survival times. Moreover, the expression of NPR3 was increased but the expression of PD-1, PD-L1, and CTLA-4 was decreased in the high-risk group compared to the low-risk group. In addition, compared with si-NC, si-NPR3 suppressed proliferation and migration but promoted apoptosis in both MDA-MB-231 and MCF-7 cells. This study presents a model for predicting survival outcomes and provides a strategy to guide effective personalized immunotherapy in BC patients.

show abstract

“…A previous study reported that NPR3 might be a potential biomarker in breast cancer outcome prediction. 31 The identification of novel stage-specific biomarkers has attracted increasing attention from researchers in CRC progression. A previous study have identified that DYNC1H1, GRIN2A, and GRM1 as new driving genes for CRC stage II progression, IGF1R, CPS1, SPTA1, and DSP as new hub driving genes for CRC stage III progress, and GSK3B, GGT1, and EIF2B5 as new hub driving genes for CRC stage IV.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study reported that NPR3 might be a potential biomarker in breast cancer outcome prediction. 31…”

Section: Discussionmentioning

confidence: 99%

Low Expression of AGPAT5 Is Associated With Clinical Stage and Poor Prognosis in Colorectal Cancer and Contributes to Tumour Progression

Zang

Sun

Xiu

et al. 2022

Clin Med Insights Oncol

View full text Add to dashboard Cite

Background: Colorectal cancer (CRC) has a high prevalence and poor prognosis. This study aimed to identify biomarkers related to the clinical stage (I-IV) of CRC. Methods: The LinkedOmics database was used as the discovery cohort, and two Gene Expression Omnibus (GEO) databases (GSE41258 and GSE422848) served as validation cohorts. The trend test of genes related to clinical stage (I-IV) of CRC patients was identified by the Jonckheere-Terpstra test. The cBioPortal database, Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan databases were used to explore the expression change and prognostic value of clinical stage-related genes in CRC patients. CRC cells overexpressed AGPAT5 were constructed and used for cell counting kit-8 (CCK-8), flow cytometric, and wound healing assays in vitro. Results: We identified four clinical stage-related genes, GSR, AGPAT5, CRLF1, and NPR3, in CRC. The CNA frequencies of GSR, CRLF1, AGPAT5, and NPR3 occurred in 11%, 2.4%, 13%, and 3% of patients, respectively. The expression of GSR and AGPAT5 tended to decrease with CRC stage (I-IV) progression, and the expression of CRLF1 and NPR3 tended to increase with CRC stage (I-IV) progression. Compared with the normal group, AGPAT5 expression was markedly decreased in stage IV CRC. Higher GSR and AGPAT5 expression levels were associated with better overall survival (OS) and disease-free survival (DFS) in CRC patients. Lower CRLF1 and NPR3 expression levels were associated with better OS and DFS in CRC. GSR, CRLF1, AGPAT5, and NPR3 expression were related to CRC progression, microsatellite instability, and tumour purity in CRC. Furthermore, AGPAT5 was downregulated in CRC cell lines, and overexpression of AGPAT5 inhibited cell proliferation and migration and promoted cell apoptosis in CRC cells. Conclusion: Low AGPAT5 expression may serve as a poor prognostic factor and clinical stage biomarker in CRC. In addition, AGPAT5 acts as a tumour suppressor in CRC progression.

show abstract

Assessing the prognostic value of stemness-related genes in breast cancer patients

Cited by 6 publications

References 49 publications

Baseline Mutations and Up-Regulation of PI3K-AKT Pathway Serve as Potential Indicators of Lack of Response to Neoadjuvant Chemotherapy in Stage II/III Breast Cancer

Baseline Mutations and Up-Regulation of PI3K-AKT Pathway Serve as Potential Indicators of Lack of Response to Neoadjuvant Chemotherapy in Stage II/III Breast Cancer

A novel immune score model predicting the prognosis and immunotherapy response of breast cancer

Low Expression of AGPAT5 Is Associated With Clinical Stage and Poor Prognosis in Colorectal Cancer and Contributes to Tumour Progression

Contact Info

Product

Resources

About