EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer

Wang, Chaoqun; Li, Yang; Huang, Bifei; Zhao, Yongming; Yuan, Hui; Guo, Dadong; Su, Chen-Ming; Hu, Guoqing; Wang, Qian; Long, Tengyun; Wang, Yan; Tang, Chih‐Hsin; Li, Xiaoni

doi:10.1038/s41598-017-15939-9

Cited by 41 publications

(35 citation statements)

References 41 publications

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“…Fumagalli C et al (8) previously found that patients with TNBC carrying a silencing mutation in the O6-methylguanine DNA methyltransferase gene are associated with an increase in the susceptibility for alkylating agents. Wang et al (10) found that epidermal growth factor induced the expression of Fascin-1 through the activation of MAPK, which lead to poorer relapse-free survival and overall survival for patients with TNBC. However, since TNBC is associated with poor prognosis, identification of novel molecular biomarkers and development of treatment strategies are urgently sorted for unravelling the possible mechanisms of TNBC progression or improving patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of a prognosis‑associated signature associated with energy metabolism in triple‑negative breast cancer

et al. 2020

Oncol Rep

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At present, a large number of exciting results have been found regarding energy metabolism within the triple-negative breast cancer (TNBC) field. Apart from aerobic glycolysis, a number of other catabolic pathways have also been demonstrated to participate in energy generation. However, the prognostic value of energy metabolism for TNBC currently remains unclear. In the present study, the association between gene expression profiles of energy metabolism and outcomes in patients with TNBC was examined using datasets obtained from the Gene Expression Omnibus and The Cancer Genome Atlas. In total, four robust TNBC subtypes were identified on the basis of negative matrix factorization clustering and gene expression patterns, which exhibited distinct immunological, molecular and prognostic (disease-free survival) features. The differentially expressed genes were subsequently identified from the subgroup that demonstrated the poorest prognosis compared with the remaining 3 subgroups, where their biological functions were assessed further by means of gene ontology enrichment analysis. Any signatures found to be associated with energy metabolism were then established using the Cox proportional hazards model to assess patient prognosis. According to results of Kaplan-Meier analysis, the constructed signature consisting of eight genes that were associated with energy metabolism distinguished patient outcomes into low-and high-risk groups. In addition, this signature, which was found to be markedly associated with the clinical characteristics of the patients, served as an independent factor in predicting TNBC patient prognosis. According to gene set enrichment analysis, the gene sets related to the high-risk group participated in the MAPK signal transduction pathway, focal adhesion and extracellular matrix receptor interaction, whilst those related to the low-risk group were revealed to be mainly associated with mismatch repair and propanoate metabolism. Findings from the present study shed new light on the role of energy metabolism within TNBC, where the eight-gene signature associated with energy metabolism constructed can be utilized as a new prognostic marker for predicting survival in patients with TNBC.

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Section: Discussionmentioning

confidence: 99%

Identification of a prognosis‑associated signature associated with energy metabolism in triple‑negative breast cancer

et al. 2020

Oncol Rep

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“…IHC staining of paraffin-embedded tissue sections used the Envision System (Dako, Glostrup, Denmark), as described previously [ 5 , 30 ]. Primary antibodies consisted of anti-METTL14 mouse monoclonal antibody (clone CL4252, diluted at 1 : 1000; Abcam, Cambridge, England), ready-to-use anti-ER rabbit monoclonal antibody (clone SP1, Dako), ready-to-use anti-PR mouse monoclonal antibody (clone PgR636, Dako), HercepTest (Dako), and ready-to-use anti-Ki-67 mouse monoclonal antibody (clone MIB-1, Dako).…”

Section: Methodsmentioning

confidence: 99%

Downregulated METTL14 Expression Correlates with Breast Cancer Tumor Grade and Molecular Classification

Dong

Wang

Huang

et al. 2020

BioMed Research International

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It is unclear whether the methyltransferase-like 14 (METTL14) protein promotes or suppresses cancer growth. We examined the association between METTL14 expression, cancer progression, and patient prognosis in a total of 398 breast cancer tissue specimens. Significantly fewer cancer tissue specimens compared with normal breast tissue expressed high levels of METTL14 (52.8% vs. 75.0%). METTL14 expression was negatively associated with tumor grade and positively associated with patient age, estrogen, and progesterone receptor status. High METTL14 expression was more common in luminal A and luminal B tissue (75.9% and 60.8%, respectively), compared with human epidermal growth factor receptor 2- (HER2-) enriched and triple-negative breast cancer (TNBC) samples (38.2% and 18.6%, respectively). In multiple logistic regression analysis, independent predictors of METTL14 expression in breast cancer included higher tumor grade ( odds ratio OR = 0.494 , 95% confidence interval (CI): 0.289–0.844; P = 0.010 ), TNBC subtype ( OR = 0.109 , 95% CI: 0.054–0.222; P < 0.001 ), and HER2-enriched subtype ( OR = 0.298 , 95% CI: 0.156–0.567; P < 0.001 ). No clear relationship was observed between patient prognosis and METTL14 expression. It appears that downregulated METTL14 expression in breast cancer is associated with tumor grade and molecular classification.

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“…IHC staining of paraffin-embedded tissue array sections was conducted using the Envision System (Dako, Glostrup, Denmark), as described previously 25 , 26 . Briefly, the sections were submerged in boiling sodium citrate (pH, 6.0) for 2 min in a pressure cooker.…”

Section: Methodsmentioning

confidence: 99%

Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis

Wang

Huang

Wang

et al. 2020

Sci Rep

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The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation. According to its function, HMGB1 shuttles between the cell nucleus and cytoplasm, assisting with nucleosome stabilization and gene transcription, or localizing in the cell membrane for outgrowth. The clinicopathologic and prognostic significance of these different subcellular locations and their correlation has been unclear in colorectal cancer (CRC). We found significantly higher rates of nuclear HMGB1 expression in CRC and colorectal adenoma tissue samples (84.0% and 92.6%, respectively) than in normal colorectal tissue (15.0%) and a significantly higher rate of positive cytoplasmic HMGB1 expression in CRC tissue (25.2%) compared with colorectal adenoma (11.8%) and normal colorectal tissue (0.0%). Positive cytoplasmic HMGB1 expression was associated with high-grade CRC, a poor prognosis, and was negatively correlated with strongly positive nuclear HMGB1 expression in CRC tissue specimens (r = – 0.377, P = 0.000). CRC patients with strongly positive nuclear HMGB1 expression had a better survival prognosis than other CRC patients. Preventing nuclear plasma translocation of HMGB1 may be a new strategy for CRC management.

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EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer

Cited by 41 publications

References 41 publications

Identification of a prognosis‑associated signature associated with energy metabolism in triple‑negative breast cancer

Identification of a prognosis‑associated signature associated with energy metabolism in triple‑negative breast cancer

Downregulated METTL14 Expression Correlates with Breast Cancer Tumor Grade and Molecular Classification

Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis

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