Discovery of a proliferation essential gene signature and actin-like 6A as potential biomarkers for predicting prognosis and neoadjuvant chemotherapy response in triple-positive breast cancer.

BACKGROUND: Patients with triple-positive breast cancer (TPBC) have a higher risk of recurrence and lower survival rates than patients with other luminal breast cancers. However, there are few studies on the predictive biomarkers of prognosis and treatment responses in TPBC. METHODS: Proliferation essential genes (PEGs) were acquired from clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) technology, and cohorts of patients with TPBC were obtained from public databases and our cohort. To develop a TPBC-PEG signature, Cox regression and least absolute shrinkage and selection operator regression analyses were applied. Functional analyses were performed with gene set enrichment analysis. The relationship between candidate genes and neoadjuvant chemotherapy (NACT) sensitivity was explored via real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) on the basis of clinical samples. RESULTS: Among 900 TPBC-PEGs, 437 showed significant differential expression between TPBC and normal tissues. Three prognostic PEGs (actin-like 6A [ACTL6A], chaperonin containing TCP1 subunit 2 [CCT2], and threonyl-TRNA synthetase [TARS]) were identified and used to construct the PEG signature. Patients with high PEG signature scores exhibited a worse overall survival and lower sensitivity to NACT than patients with low PEG signature scores. RT-qPCR results indicated that ACTL6A and CCT2 expression were significantly upregulated in patients who lacked sensitivity to NACT. IHC results showed that the ACTL6A protein was highly expressed in patients with NACT resistance and nonpathological complete responses. CONCLUSIONS: This efficient PEG signature prognostic model can predict the outcomes of TPBC. Furthermore, ACTL6A expression level was associated with the response to NACT, and could serve as an important factor in predicting prognosis and drug sensitivity of patients with TPBC.

The value of oral selective estrogen receptor degraders in patients with HR-positive, HER2-negative advanced breast cancer after progression on ≥ 1 line of endocrine therapy: systematic review and meta-analysis.

BACKGROUND: Currently, the value of oral selective estrogen receptor degraders (SERDs) for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (aBC) after progression on ≥ 1 line of endocrine therapy (ET) remains controversial. We conducted a meta-analysis to evaluate progression-free survival (PFS) and safety benefits in several clinical trials. MATERIALS AND METHODS: Cochrane Library, Embase, PubMed, and conference proceedings (SABCS, ASCO, ESMO, and ESMO Breast) were searched systematically and comprehensively. Random effects models or fixed effects models were used to assess pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for treatment with oral SERDs versus standard of care. RESULTS: A total of four studies involving 1,290 patients were included in our analysis. The hazard ratio (HR) of PFS showed that the oral SERD regimen was better than standard of care in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET (HR: 0.75, 95% CI: 0.62-0.91, p = 0.004). In patients with ESR1 mutations, the oral SERD regimen provided better PFS than standard of care (HR: 0.58, 95% CI: 0.47-0.71, p < 0.00001). Regarding patients with disease progression following previous use of CDK4/6 inhibitors, PFS benefit was observed in oral SERD-treatment arms compared to standard of care (HR: 0.75, 95% CI: 0.64-0.87, p = 0.0002). CONCLUSIONS: The oral SERD regimen provides a significant PFS benefit compared to standard-of-care ET in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET. In particular, we recommend oral SERDs as a preferred choice for those patients with ESR1m, and it could be a potential replacement for fulvestrant. The oral SERD regimen is also beneficial after progression on CDK4/6 inhibitors combined with endocrine therapy.

The trade-off of post-mastectomy radiotherapy usage for the breast cancer patients aged 70 years or older: a study based on SEER database.

BACKGROUND: This study aimed to investigate the role of post-mastectomy radiotherapy (PMRT) in the female aged 70 years or older diagnosed with breast cancer, which is still controversial. METHODS: This retrospective study enrolled female breast cancer women aged 70 + years following mastectomy from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce covariable imbalance. A nomogram was created to predict the 1,3,5-years overall survival (OS) and divide patients into three risk groups. RESULTS: After matching, PMRT were associated with significant improvement in breast cancer-specific survival (BCSS) and OS (p < 0.001). By contrast, the BCSS and OS benefit from PMRT were not significant in patients with T1N1 tumor (BCSS: HR = 0.716, p = 0.249;OS:HR = 0.908, p = 0.572), and T2N1 tumor (BCSS:HR = 0.866, p = 0.289;OS:HR = 0.879, p = 0.166). Stratified by subtype, the HR+/HER-2- subtype and the HR-/HER-2- subtype (all p < 0.001) have a significant prolonged survival, yet not significant BCSS difference are shown in the HER-2 + tumor. In the low-risk group as determined by the nomogram, the use of PMRT did not significantly improve OS (p = 0.203). CONCLUSIONS: This study demonstrated that PMRT improves the survival of females with elderly breast cancer, while for T1-2N1 breast cancer patients, the omission of PMRT could be considered. Furthermore, the nomogram we constructed could be used as a decision tool for the omission of PMRT in low-risk elderly patients.

Prognosis and local treatment strategies of breast cancer patients with different numbers of micrometastatic lymph nodes.

BACKGROUND: Lymph node micrometastasis is an important prognostic factor in breast cancer, but patients with different numbers of involved lymph nodes are all divided into the same N1mi stage without distinction. We designed this study to compare the prognosis and local treatment recommendations of N1mi breast cancer patients with different numbers of micrometastatic lymph nodes. PATIENTS AND METHODS: A total of 27,032 breast cancer patients with T1-2N1miM0 stage from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2019) who underwent breast surgery were included in this retrospective study. Patients were divided into three groups for prognosis comparison according to the number of micrometastatic lymph nodes: N1mi with 1 (Nmi = 1), 2 (Nmi = 2), or more (Nmi ≥ 3) involved lymph nodes. We explored the characteristics and survival outcomes of the population receiving different local treatments, including different axillary surgery types and whether receiving radiotherapy or not. Univariate and multivariate Cox proportional hazards regression analysis were used to compare the overall survival (OS) and breast cancer-specific survival (BCSS) in different groups. Stratified analyses and interaction analyses were also applied to explore the predictive significance of different involved lymph nodes numbers. Propensity score matching (PSM) method was utilized to balance the differences between groups. RESULTS: Univariate and multivariate Cox regression analysis indicated that nodal status was an independent prognostic factor. After adjustment for other prognostic factors, there was a significant difference in prognosis between Nmi = 1 group and Nmi = 2 group [adjusted hazard ratio (HR) 1.145, 95% confidence interval (CI): 1.047-1.251, P = 0.003], and patients with Nmi ≥ 3 group had a significantly poorer prognosis (adjusted HR 1.679, 95% CI 1.589-2.407; P < 0.001). The proportion of N1mi patients only underwent sentinel lymph nodes biopsy (SLNB) gradually increased from 2010 (Ptrend < 0.001). After adjusting for other factors, N1mi patients who underwent axillary lymph nodes dissection (ALND) was associated with significant survival benefit than SLNB (adjusted HR 0.932, 95%CI 0.874-0.994; P = 0.033), the same goes for receiving radiotherapy (adjusted HR 1.107, 95%CI 1.030-1.190; P = 0.006). Further stratified analysis showed that in the SLNB subgroup, radiotherapy was associated with a significant survival benefit (HR 1.695, 95%CI 1.534-1.874; P < 0.001), whereas in the ALND subgroup, there was no significant prognostic difference with or without radiotherapy (HR 1.029, 95%CI 0.933-1.136; P = 0.564). CONCLUSION: Our study indicates that the increasing number of lymph node micrometastases was associated a worse prognosis of N1mi breast cancer patients. In addition, ALND does provide a significant survival benefit for these patients, while the benefit from local radiotherapy may be of even greater importance.

Nanomaterials-based electrochemical sensors for the detection of natural antioxidants in food and biological samples: research progress.

Antioxidants are healthy substances that are beneficial to the human body and exist mainly in natural and synthetic forms. Among many kinds of antioxidants, the natural antioxidants have great applications in many fields such as food chemistry, medical care, and clinical application. In recent years, many efforts have been made for the determination of natural antioxidants. Nano-electrochemical sensors combining electrochemistry and nanotechnology have been widely used in the determination of natural antioxidants due to their unique advantages. Therefore, a large number of nanomaterials such as metal oxide, carbon materials, and conducting polymer have attracted much attention in the field of electrochemical sensors due to their good catalytic effect and stable performance. This review mainly introduces the construction of electrochemical sensors based on different nanomaterials, such as metallic nanomaterials, metal oxide nanomaterials, carbon nanomaterials, metal-organic frameworks, polymer nanomaterials, and other nanocomposites, and their application to the detection of natural antioxidants, including ascorbic acid, phenolic acids, flavonoid, tryptophan, citric acid, and other natural antioxidants. In the end, the limitations of the existing nano-sensing technology, the latest development trend, and the application prospect for various natural antioxidant substances are summarized and analyzed. We expect that this review will be helpful to researchers engaged in electrochemical sensors.

Impact of Postoperative Radiotherapy on Survival of Patients With de novo Stage IV Breast Cancer: A Population-Based Study From the SEER Database.

Purpose: In our study, we aimed to evaluate the role of postoperative radiotherapy for patents with de novo stage IV breast cancer. Patients and Methods: Patients diagnosed with stage IV breast cancer from 2010 to 2016 were selected from the Surveillance, Epidemiology, and End Result (SEER) database. Those patients who received both chemotherapy and surgery and lived longer than 6 months were divided into radiotherapy and non-radiotherapy groups. Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to estimate the survival outcomes before and after being 1:1 propensity score matched (PSM). Subgroup analyses stratified by age, subtype, status of distant metastasis, and surgery type were also performed. Results: Among 1,935 patients, 52% (1006) underwent radiotherapy while the non-radiotherapy group contained 48% (929). After PSM, a total of 1,520 patients in two groups of 760 patients were enrolled in this analysis. Kaplan-Meier and the multivariate survival analysis demonstrated that the radiotherapy group presented with a better prognosis compared to the non-radiotherapy group (after PSM, BCSS: Hazard Ratio, 0.697; 95% confidence interval, 0.59-0.823; P < 0.001; OS: Hazard Ratio, 0.707; 95% confidence interval, 0.601-0.831; P < 0.001). Further subgroup analyses showed the Luminal subtype (HR+/HER2-), triple-negative breast cancer (TNBC), and bone-only metastasis patients presented with the most promising survival in the radiotherapy group. Conclusions: Postoperative radiotherapy is associated with a significant survival advantages in BCSS and OS. It can be an optimal supplementary treatment for stage IV patients after surgery, especially for Luminal subtype, TNBC, and patients with a low metastatic burden.

Association of Axillary Lymph Node Evaluation With Survival in Women Aged 70 Years or Older With Breast Cancer.

BACKGROUND: Survival in elderly patients undergoing sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) has not been specifically analyzed. This study aimed to explore the association between different types of axillary lymph node (ALN) evaluations and survival of elderly breast cancer patients. METHODS: A retrospective cohort study was conducted of invasive ductal breast cancer patients 70 years and older in the Surveillance, Epidemiology, and End Results database (2004-2016). Analyses were performed to compare the characteristics and survival outcomes of patients who received surgical lymph node dissection and those who did not. Breast cancer specific survival (BCSS) and overall survival were compared by using Cox proportional hazards regression analysis and propensity score matching (PSM) methods to account for selection bias from covariate imbalance. RESULTS: Of the 75,950 patients analyzed, patients without ALN evaluation had a significantly worse prognosis, while there was no significant difference for BCSS between using a sentinel lymph node biopsy (SLNB) and an axillary lymph node dissection (ALND) after adjustment for known covariates [adjusted hazard ratio (HR) = 0.991, 95% confidence interval (CI) = 0.925-1.062, p = 0.800]. In the stratification analyses after PSM, the ALND did not show a significant BCSS advantage compared with SLNB in any subgroups except for the pN1 stage or above. Furthermore, after PSM of the pN1 stage patients, SLNB was associated with a significantly worse BCSS in hormone receptor negative (HR-) patients (HR = 1.536, 95%CI = 1.213-1.946, p < 0.001), but not in the hormone receptor positive (HR+) group (HR = 1.150, 95%CI = 0.986-1.340, p = 0.075). CONCLUSION: In our study, ALND does not yield superior survival compared with SLNB for elderly patients with pN1 stage HR+ breast cancer. Although our findings are limited by the bias associated with retrospective study design, we believe that in the absence of results from randomized clinical trials, our findings should be considered when recommending the omission of ALND for elderly breast cancer patients.

Validation of the Prognostic Significance of the Prognostic Stage Group According to the Eighth Edition of American Cancer Joint Committee on Cancer Staging System in Triple-Negative Breast Cancer: An Analysis From Surveillance, Epidemiology, and End Results 18 Database.

BACKGROUND: The eighth edition of the American Cancer Joint Committee on Cancer (AJCC) staging system for breast cancer put forward the prognostic stage groups for the first time based on the traditional anatomic tumor-node-metastasis staging system. Our study intends to validate the predictive significance of the eighth edition staging system in triple-negative breast cancer (TNBC) patients. MATERIALS AND METHODS: We collected and accessed 26,589 eligible cases of TNBC from the Surveillance, Epidemiology, and End Results database (2010-2015) and reclassified the patient cohort according to the eighth edition of the AJCC staging system into anatomic and prognostic stages. RESULTS: The results showed that more than half of the patients upstaged in the prognostic stage when compared with the anatomic stage. By comparing with the anatomic stage, the prognostic stage had a higher likelihood ratio and linear trend χ2 values. The prognostic stage group also had higher Akaike information criterion and Bayesian information criterion values than the anatomic stage group. CONCLUSIONS: The prognostic staging system in TNBC patients performs more optimistic prognostic stratification and predictability than the anatomic staging system. Moreover, the latest AJCC staging system has a milestone importance to the history of breast cancer staging system.

Nitrogen Doped Graphene Supported Pt Nanoflowers as Electrocatalysts for Oxidation of Formaldehyde.

A facile Pt nanoflowers/nitrogen-doped graphene (PtNFs/NG) electrocatalyst was prepared via depositing Pt nanoflowers (PtNFs) onto the nitrogen-doped graphene (NG) matrix with urea as the nitrogen source and PtNFs/NG modified glassy carbon electrode (GCE) was prepared by electro-chemical method. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Raman spectroscope, X-ray photoelectron spectroscopy (XPS) and Scanning electron microscope (SEM) were used to characterize the resulting composites. Also oxidation of formaldehyde on the resulting PtNFs/NG modified electrode was investigated. The influence of deposition time, electrodeposition potential and formaldehyde concentration on electrooxidation of formaldehyde was detected, the experimental results indicate the high performance of PtNFs/NG catalyst for formaldehyde oxidation is at electrodeposition time of 300 s with the applied potential of −0.3 V. Electrochemical process, electrocatalytic stability and chronoamperometry were also inspected, it was indicated that formalde-hyde oxidation reaction on the PtNFs/NG electrode is diffusion-controlled and PtNFs/NG exhibits a high catalytic activity, stability as well as excellent poisoning-tolerance towards formaldehyde oxidation, which is attributed to the synergistic effect of PtNFs and NG. It turns out that PtNFs/NG can be used in direct liquid-feed fuel cells as a promising alternative catalyst.

[Determination of cholesterol in drainage oil by solid phase extraction-gas chromatography-mass spectrometry].

An effective method was developed for the determination of cholesterol in drainage oil by solid phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS). Firstly, the samples were purified by SPE on a column packed with silica. An extraction yield of 97% was obtained when a 20 mL of ethyl ether/n-hexane mixture (0.6: 99.4, v/v) was used for washing the SPE column, and 10 mL of the same solvent mixture (15: 85, v/v) for desorbing cholesterol from the SPE column. Then the final extract was determined by GC-MS with electron impact ion source. The cholesterol was characterized according to retention time and characteristic fragments (m/z 213, 275, 301, 368, 386), and was quantitatively determined by external standard method in selected ion monitoring mode. The fragment of m/z 386 was selected as the target ion, and m/z 213 and m/z 275 were used as the reference ions. The average recovery was from 91.7% to 101%, and the relative standard deviations (RSDs) were below 6%, and the detection limit was 0.01 mg/L. A good linearity was obtained in the cholesterol concentration range of 0.24 - 6.0 mg/L with the correlation coefficient of 0.999 6. The proposed method can be used to determine the cholesterol content in oil accurately, and the detection result can be one of the criteria judging the existence of drainage oil in edible oil.

Generation of a mouse monoclonal antibody recognizing both the native and denatured forms of human VEGF.

Vascular endothelial growth factor (VEGF) and its related member, placental growth factor (PlGF), play important roles in stimulating vascular growth (angiogenesis) in both physiological conditions such as embryonic development and pathological conditions such as inflammation and tumor growth. Development of monoclonal antibodies (MAbs) capable of blocking the interaction of VEGF and its receptors, which in turn block VEGF-mediated angiogenesis, has become a novel and very powerful approach for cancer management. Here we report the generation of a mouse monoclonal antibody M23, which binds to both the natural and denatured forms of human VEGF165, as well as to two other major VEGF isoforms (VEGF121 and VEGF189) being tested. MAb M23 does not bind to other VEGF-related proteins such as PlGF. This MAb will have great future potential in VEGF-related research, diagnosis, and treatment.