MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study

Jiang, Weihua; Xing, Xiao-Liang; Zhang, Chenguang; Lee, Yi; Xu, Wenting; Jiang, Ou; Zhu, Ning

doi:10.3389/fonc.2021.604801

Cited by 14 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been hypothesized that useful indicators of prognosis can be found based on differences in the degree of expression between normal and cancer tissues, and patients with high FASN expression level have been reported to show lower disease-free survival and decreased survival rate [ 31 ]. High FASN expression was identified in 45% of TNBC cases [ 15 ] and high-FASN groups have been significantly associated with positive nodal status [ 15 , 16 ]. Therefore, FASN has emerged as a potential target, and FASN inhibitors are being evaluated in clinical trials [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Of them, fatty acid synthetase (FASN) is a lipid-producing enzyme that is expressed at low level in normal human tissues but is reported to be highly expressed in breast, colon, prostate, and ovarian cancer [ 11 – 14 ]. The role of FASN as a prognostic factor in breast cancer has been published in previous studies [ 15 , 16 ].…”

mentioning

confidence: 99%

“…However, few studies have identified the expression of FASN level in TNBC [ 15 , 16 ]. The absence of effective targeted therapy for TNBC and its poor prognosis led to exploration of the role of FASN as a potential target for TNBC therapy [ 17 ].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Fatty acid synthetase expression in triple-negative breast cancer

Park

Han

Lim

et al. 2022

J Pathol Transl Med

View full text Add to dashboard Cite

Background: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolismrelated protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC. Methods: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0-1+ FASN staining were grouped as low-grade FASN and patients with 2+-3+ FASN staining as high-grade FASN. Results: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low-and high-FASN expression groups. Conclusions: We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Fatty acid synthetase expression in triple-negative breast cancer

Park

Han

Lim

et al. 2022

J Pathol Transl Med

View full text Add to dashboard Cite

show abstract

“…In recent years, increasing evidence has highlighted its important role in many cancers. High FASN expression is related to poor prognosis and metastasis in breast cancer ( 40 , 41 ). In contrast, FASN inhibition both limits tumor–cell migration and invasiveness, and increases tumor sensitivity to drug therapy ( 42 – 44 ).This evidence, along with our findings, suggests that, while CPT1B is rate-limiting in fatty acid catabolism, FASN is the key regulator of fatty acid anabolism; together, they regulate the fatty acid metabolic pool and may play important role in progression and treatment of cancers.…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid Synthase Is the Key Regulator of Fatty Acid Metabolism and Is Related to Immunotherapy in Bladder Cancer

et al. 2022

View full text Add to dashboard Cite

Fatty acid metabolism (FAM) genes are potentially useful for predicting prognosis and immunotherapy response in bladder cancer (BC). To examine this, we constructed a prognostic model and identified key FAM genes in BC. Using transcriptional expression profiles and clinical data of BC patients from public datasets and Changhai (CH) hospital, we built and validated a risk-score model based on 13 prognostic FAM genes. Differential gene expression identified fatty acid synthase (FASN) as central to fatty acid metabolism in BC. FASN was differentially expressed between normal and tumor tissue, and was related to survival. In the CH dataset, FASN independently predicted muscle-invasive BC. FASN differential expression was significantly related to immune-cell infiltration and patients with low FASN expression responded better to immune checkpoint inhibitor (ICI) treatment. SREBF1 was predicted as the most significant transcription factor for FASN. Competing endogenous RNA network analysis suggested that lncRNA AC107027.3 may upregulate FASN by competitively binding miR-27A-3p, thereby regulating the immunotherapy response in BC. Dasatinib and temsirolimus are potential FASN-targeting drugs. Our model efficiently predicted prognosis in BC. FASN is central to fatty acid metabolism, and a potential indicator and regulator of ICI treatment.

show abstract

“…FASN promotes the formation of the lipid raft phospholipid HER2 transduction complex on cell membranes by catalyzing fatty acid synthesis, which is subsequently involved in activating the PI3K (phosphoinositide 3-kinase)/AKT/mTOR (mammalian target of rapamycin) pathways ( 19 , 20 ). FASN overexpression was found in many types of tumor cells including breast cancer ( 21 – 23 ). Whether FASN expression had impact on the prognosis in patients with breast cancer is elusive.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and clinicopathological significance of fatty acid synthase in breast cancer: A systematic review and meta-analysis

et al. 2023

View full text Add to dashboard Cite

BackgroundAberrant expression of fatty acid synthase (FASN) was demonstrated in various tumors including breast cancer. A meta-analysis was conducted to investigate the role of FASN in breast cancer development and its potential prognostic significance.MethodsThe Web of Science, PubMed, Embase, and Cochrane Library databases were searched to identify studies that evaluated the relationship between FASN expression and overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS) of breast cancer patients. To analyze the clinicopathological and prognostic values of FASN expression in breast cancer, pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were clustered based on random-effects models. To confirm whether the findings were stable and impartial, a sensitivity analysis was performed, and publication bias was estimated. Data were analyzed using Engauge Digitizer version 5.4 and Stata version 15.0.ResultsFive studies involving 855 participants were included. Patients with higher FASN expression did not have a shorter survival period compared to those with lower FASN expression (summary HR: OS, 0.73 [95% CI, 0.41-1.32; P=0.300]; DFS/RFS, 1.65 [95% CI, 0.61-4.43; P=0.323]). However, increased FASN expression was correlated with large tumor size (OR, 2.04; 95% CI, 1.04-4.00; P=0.038), higher human epidermal growth factor receptor 2 (HER2) positivity (OR, 1.53; 95% CI, 1.05-2.23; P=0.028). No significant associations were observed between FASN expression and histological grade (OR, 0.92; 95% CI, 0.41-2.04; P=0.832), Tumor Node Metastasis (TNM) stage (OR, 1.11; 95% CI, 0.49-2.53; P=0.795), nodal metastasis (OR, 1.42; 95% CI, 0.84-2.38; P=0.183), Ki-67 labelling index (OR, 0.64; 95% CI, 0.15-2.63; P=0.533), estrogen receptor (ER) status (OR, 0.90; 95% CI, 0.61-1.32; P=0.586), or progesterone receptor (PR) status (OR, 0.67; 95% CI, 0.29-1.56; P=0.354).ConclusionFASN is associated with HER2 expression and may contribute to tumor growth, but it has no significant impact on the overall prognosis of breast cancer.

show abstract

MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study

Cited by 14 publications

References 33 publications

Fatty acid synthetase expression in triple-negative breast cancer

Fatty acid synthetase expression in triple-negative breast cancer

Fatty Acid Synthase Is the Key Regulator of Fatty Acid Metabolism and Is Related to Immunotherapy in Bladder Cancer

Prognostic and clinicopathological significance of fatty acid synthase in breast cancer: A systematic review and meta-analysis

Contact Info

Product

Resources

About