Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.

Multi-omics approaches identify SF3B3 and SIRT3 as candidate autophagic regulators and druggable targets in invasive breast carcinoma

Autophagy is a critical cellular homeostatic mechanism,and its dysfunction is linked to invasive breast carcinoma(BRCA).Recently,several omics methods have been applied to explore autophagic regulators in BRCA;however,more reliable and robust approaches for identifying crucial regulators and druggable targets remain to be discovered.Thus,we report here the results of multi-omics approaches to identify potential autophagic regulators in BRCA,including gene expression(EXP),DNA methylation(MET)and copy number alterations(CNAs)from The Cancer Genome Atlas(TCGA).Newly identified candidate genes,such as SF3 B3,TRAPPC10,SIRT3,MTERFD1,and FBXO5,were confirmed to be involved in the positive or negative regulation of autophagy in BRCA.SF3 B3 was identified firstly as a negative autophagic regulator,and siRNA/shRNA-SF3 B3 were shown to induce autophagyassociated cell death in in vitro and in vivo breast cancer models.Moreover,a novel small-molecule activator of SIRT3,1-methylbenzylamino amiodarone,was discovered to induce autophagy in vitro and in vivo.Together,these results provide multi-omics approaches to identify some key candidate autophagic regulators,such as the negative regulator SF3 B3 and positive regulator SIRT3 in BRCA,and highlight SF3 B3 and SIRT3 as new druggable targets that could be used to fill the gap between autophagy and cancer drug development.

Vascular Endothelial Growth Factor Expression in Invasive Ductal Carcinoma of Breast

Objective： To detect the expression of VEGF and MVD count in invasive ductal carcinoma of breast to clarify the association of VEGF expression and MVD count with the clinicopathologic features. Methods： The expressions of VEGF, ER, PR, C-erbB-2 and MVD count in 88 cases of invasive ductal carcinoma of breast were examined by immunohistochemistry staining （SP-method）. Results： Sixty-two out of the eighty-eight specimens of breast carcinoma （70.45%） showed positive expression of VEGF. The positive rate of VEGF in cases with lymph node metastasis was higher than that without lymph node metastasis （P〈0.05）. The positive rate of VEGF in stage IIb-Ⅲ was higher than that in stage Ⅰ-Ⅱa （P〈0.05）. The positive rate of VEGF in C-erbB-2 positive group was higher than that in C-erbB-2 negative group （P〈0.05）. Higher expression of VEGF was observed in cases with higher tissue differentiation degree （P〈0.05）. Also, significant higher MVD count was observed in cases with higher tissue differentiation degree （P〈0.01）. The MVD count increased significantly with the increase of the expression of VEGF （P〈0.01）. Conclusion： The result of this study suggested that in invasive ductal carcinoma of breast, angiogenesis and metastasis were mediated mainly by VEGF. The expression of VEGF and MVD might be reference predictors for the biological behavior of breast carcinoma. The antiangiogenic therapy which used VEGF as a target would become a new method to treat patients who were C-erbB-2 positive in the future.

Clinical Value Analysis of Ultrasonography and MRI in Diagnosis of Invasive Micropapillary Carcinoma of Breast

Objective:To investigate the diagnostic value of invasive micropapillary carcinoma(IMPC)by ultrasonography and MRI.Method:63 female patients with IMPC were selected,all of which were confirmed by pathological examination,and were assigned to the IMPC group.In the same period,40 patients with invasive ductal carcinoma(IDC group)were selected for diagnostic efficacy control.The efficacy indexes of accuracy,sensitivity,specificity,positive prediction rate and negative prediction rate were 73.0%,65.9%,89.5%,93.5%,46.9%,respectively.The efficiency indexes of accuracy,sensitivity,specificity,positive prediction rate and negative prediction rate of ultrasound combined with breast MRI were 93.6%,93.2%,94.7%,97.6%,85.7%.Ultrasonography combined with MRI has more application value in the diagnosis of IMPC.

Metastatic Lobular Carcinoma of the Breast Presenting with Small Bowel Metastases:Case Report and Literature Review

Introduction: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, representing 5% to 15% of invasive tumors. ILC tends to spread to bones, lungs, central nervous system, reproductive organs, and the gastrointestinal tract (GI tract). The most commonly affected organs in the GI tract are the stomach, small intestine, followed by colon and rectum. Case presentation: A 78-year-old woman who was referred to our institution after having a bowel obstruction that required a diagnostic laparoscopy where they identified an obstructing ulcerative lesion in the distal ileum that was managed with a segmental bowel resection. Pathology report showed an invasive lobular breast carcinoma that occluded 90% of the bowel lumen. A PET/CT scan revealed a left breast tumor with increased metabolism. The patient was staged as a clinical cT4b, cN0, cM1 left breast invasive lobular carcinoma (ER/PgR positive, HER-2 negative). She was managed with endocrine therapy with Letrozole (an eight-week course). A follow-up PET/CT showed a peritoneal hypermetabolic nodule adjacent to the previous ileal anastomosis. The lesion decreased in size and metabolic activity. In a multidisciplinary fashion, the endocrine therapy was extended for another three months. Another follow-up PET/CT scan was performed three months after the identification of the peritoneal implant that showed that the nodule increased in size and in metabolism. The lesion continued to decrease significantly in size and became metabolically inactivity. Due to the good breast response and the possibility that the ileal nodule could be a granuloma, she underwent an exploratory laparoscopy with excision of the peritoneal nodule, and a modified left radical mastectomy with immediate breast reconstruction (complex wound closure). The final pathology report of the nodule was negative for malignancy. She continued on endocrine therapy and underwent whole breast irradiation four weeks after the operation. Currently, she is free of disease with no evidence of local, regional, or distant recurrence, and she is still on endocrine therapy. Discussion: The time interval between primary breast cancer and gastrointestinal involvement may range from synchronous presentation to as long as 30 years. The clinical manifestations in GI lobular breast cancer metastasis may range from non-specific complaints to acute GI symptoms, such as a bowel obstruction. There are multiple controversies in the management of ILC. Systemic treatment should be initiated as soon as possible. Indications for postmastectomy radiotherapy are also controversial, given the propensity for multifocal/multicentric tumors and late recurrences, sometimes in atypical locations. Five years of postoperative adjuvant hormonal therapy is an option for women with poor prognosis. Remissions are observed in 32% to 53% of patients. Conclusion: Metastatic lobular carcinoma of the breast has a wide range of clinical presentations. Patients with a history of breast cancer who present with new GI tumors should have these lesions evaluated for evidence of metastasis through histopathologic and immunohistochemical analysis, this will allow for appropriate management. Currently, breast cancer management involves a multidisciplinary approach including surgery, radiotherapy, and systemic medical therapy, and the treatment must be tailored to the patient’s needs.