No abstract

In some cases of breast cancer, diagnosis of triple‐negative breast cancer (TNBC) requires further fluorescence in situ hybridization (FISH) for determining human epidermal growth factor receptor 2 (HER2) status. However, few cases undergo FISH in China, leading to difficulty regarding subsequent treatment decisions. Here, we used immunohistochemical analysis to explore expression of fascin‐1, an actin‐bundling protein, as a diagnostic marker of TNBC. A total of 457 cases of breast cancer were divided into four molecular subtypes, including 82 cases (17.9%) of TNBC, 81 (17.7%) of HER2‐enriched, 185 (40.5%) of luminal A, and 109 (23.9%) of luminal B. Positive fascin‐1 expression was seen in 144 cases (31.5%), including 77 (16.8%) strong positive cases. Rates of positive and strong positive expression of fascin‐1 were significantly higher in cases of TNBC than in the other molecular subtypes. In all cases of breast cancer, the sensitivities and specificities of positive and strong positive fascin‐1 expression for predicting TNBC were 87.8% and 80.8%, and 78.0% and 96.5%, respectively. In cases of hormone receptor–negative breast cancer, the sensitivities and specificities of positive and strong positive fascin‐1 expression for predicting TNBC were 87.8% and 61.7%, and 78.0% and 92.6%, respectively. In 24 cases with estrogen receptor (ER)‐, PR‐, and HER2 2 +  equivocal status who underwent FISH, the sensitivity and specificity of strong positive fascin‐1 expression for predicting TNBC were 71.4% and 90.0%. These results suggest that strong positive fascin‐1 expression can be used as a diagnostic marker of TNBC.

Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.

Breast cancer is a major cause of cancer mortality worldwide. Fascin-1 (FSCN1) is an actin-binding protein found in mammalian cells, including endothelial, neuronal and mesenchymal cells. FSCN1 overexpression has been indicated in breast cancer patients. However, scant information is available regarding the association between FSCN1 single nucleotide polymorphisms (SNPs) and the risk or prognosis of breast cancer. We report on the association between 6 SNPs of the FSCN1 gene (rs56156320, rs8772, rs3801004, rs2966447, rs852479 and rs1640233) and breast cancer susceptibility as well as clinical outcomes in 316 patients with breast cancer and in 222 healthy controls. Carriers of the AC or AC + CC allele of the variant rs56156320 were at greater risk of breast cancer compared with wild-type (AA) carriers. Moreover, carriers of at least one G allele in rs3801004 were likely to progress to stage III/IV disease and lymph node metastasis. Individuals with at least one T allele at FSCN1 SNP rs2966447 were at higher risk of developing pathologic grade G3 disease. Furthermore, individuals bearing the C/C haplotype at SNPs rs56156320 and rs3801004 had nearly twice the risk of breast cancer. Our results indicate that genetic variations in the FSCN1 gene may serve as an important predictor of early-stage breast cancer.

Breast cancer is a major cause of cancer mortality worldwide. High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that participates in tumor progression, migration and metastasis. HMGB1 overexpression has been indicated in breast cancer patients. However, scant information is available regarding the association between HMGB1 single nucleotide polymorphisms (SNPs) and the risk or prognosis of breast cancer. We report on the association between 4 SNPs of the HMGB1 gene (rs1360485, rs1045411, rs2249825 and rs1412125) and breast cancer susceptibility as well as clinical outcomes in 313 patients with breast cancer and in 217 healthy controls. Patients with one G allele in the rs1360485 or rs2249825 domains are likely to progress to T2 tumor and lymph node metastasis. In addition, the presence of one G allele in SNPs rs1360485 or rs2249825 was associated with a higher risk of progressing to T2 tumor and distant metastasis amongst HER2-enriched and triple-negative breast cancer (TNBC) tumors compared with luminal A and luminal B tumors. Furthermore, having one C allele in the rs1412125 domain increased the risk of pathologic grade 3 disease in HER2-enriched and TNBC tumors. Our results indicate that genetic variations in the HMGB1 gene may serve as an important predictor of breast cancer progression and metastasis.

Emerging evidence indicates that resistin and fascin-1 may possess a causal role in the development of several types of cancers. However, the clinical significance of resistin expression in colorectal cancer (CRC) tissues is unclear, and there are no reports of any correlation between resistin and fascin-1. Our analyses explored the expression of resistin in CRC tissue and analyzed the clinical and prognostic significance of the observed positive correlation between resistin and fascin-1. The rate of strongly positive resistin expression (27.5%) was significantly higher in CRC tissues than in normal colorectal tissues (5.2%). Strongly positive resistin expression is related to multiple poor prognostic factors in CRC, including depth of tumor invasion, lymph node metastasis, and tumor stage. In this study, survival was worse in CRC patients with high levels of both resistin and fascin-1 expression than in those with high levels of only one protein or normal levels of both proteins. We suggest that a combined high level of resistin and fascin-1 expression correlates reliably with survival in CRC, so it may serve as a potential therapeutic target.

The adipokine resistin is linked with obesity, inflammation and various cancers, including breast cancer. This study sought to determine whether certain polymorphisms in the gene encoding resistin, RETN, increase the risk of breast cancer susceptibility. We analyzed levels of resistin expression in breast cancer tissue and samples from The Cancer Genome Atlas database. We also examined associations between four RETN single nucleotide polymorphisms (SNPs; rs3745367, rs7408174, rs1862513 and rs3219175) and breast cancer susceptibility in 515 patients with breast cancer and 541 healthy women without cancer. Compared with wild-type (GG) carriers, those carrying the AG genotype of the RETN SNP rs3219175 and those carrying at least one A allele in the SNP rs3219175 had a higher chance of developing breast cancer (adjusted odds ratio, AOR: 1.295, 95% confidence intervals, CI: 1.065-1.575 and 2.202, 1.701-2.243, respectively). When clinical aspects and the RETN SNP rs7408174 were examined in the breast cancer cohort, the CT genotype was linked to late-stage disease, while women with luminal A disease and at least one C allele were likely to progress to stage III/IV disease and to develop highly pathological grade III disease. Moreover, resistin-positive individuals were at greater risk than resistin-negative individuals for developing pathological grade III disease (OR: 5.020; 95% CI: 1.380-18.259). This study details risk associations between resistin and RETN SNPs in breast cancer susceptibility in Chinese Han women.

SummaryAsymptomatic carotid stenosis is common and is associated with increased risk of stroke. The relative efficacy and safety of carotid endarterectomy (CEA) and carotid stenting (CAS) in patients with asymptomatic carotid stenosis remain unclear. Five studies that recruited patients with asymptomatic but significant carotid stenosis, who underwent CEA or CAS, were included in this systematic review and meta-analysis. The analyzed outcomes included risks of stroke, myocardial infarction (MI), and death. Risk ratio (RR) and 95% confidence interval (95% CI) were calculated and pooled for meta-analysis. Pooled analysis demonstrated that compared with CEA, CAS was associated with a decreased risk of MI (RR = 0.49, 95%CI = 0.26-0.91, P = 0.023) and slightly increased risk of stroke, although not significant (RR = 1.69, 95% CI = 0.97-2.92, P = 0.063). There was no difference in the death rates between the groups (RR = 0.60, 95% CI = 0.17-2.18, P = 0.436). In the subgroup analysis, CAS was associated with a decreased risk of MI in mixed patients (RR = 0.45, 95% CI = 0.26-0.78, P = 0.005), but not in asymptomatic patients (RR = 0.549, 95% CI = 0.26-1.17, P = 0.119). Compared with CAS, CEA was associated with decreased risk of perioperative stroke and increased risk of MI; it did not affect the risk of death in patients with asymptomatic carotid stenosis. In the subgroup analysis, the decreased risk of MI after CAS was significant only in the mixed patients group. CAS was associated with higher risk of stroke but lower risk of MI than those with CEA. Both procedures appeared equivalent in terms of the risk of death.(Int Heart J 2018; 59: 550-558)