Biomarker For Breast Cancer Patients Research Articles

Inflammation-related proteins as biomarkers of treatment-related behavioral symptoms: A longitudinal study of breast cancer patients and age-matched controls

BackgroundBehavioral symptoms in breast cancer (BC) survivors have been attributed to cancer treatment and resulting inflammation. However, studies linking behavioral symptoms to BC treatment have observed patients only after some treatment. Our prospective study with pre-treatment baseline investigates post-treatment changes in inflammation-related biomarkers and whether those changes correlate with changes in symptoms. MethodsParticipants were postmenopausal women, newly-diagnosed with stage 0–3 BC before any treatment (n = 173 “patients”), and age-matched women without cancer (n = 77 “controls”), who were assessed on plasma markers [soluble tumor necrosis factor receptor type 2 (sTNF-RII), interleukin (IL)-6, IL-1 receptor antagonist (IL-1RA), C-reactive protein (CRP)]) and symptoms (Physical Functioning, Pain, Attention/concentration, Perceived Cognitive Problems, Fatigue, Sleep Insufficiency, Depression). Participants were assessed again 1 month, 1 year, and 2 years after completing primary treatment or similar interval in controls. Generalized linear mixed models tested 4 treatments (surgery alone or with chemotherapy, radiation, or both) for association with change per marker. Joint models tested change per marker for association with change per symptom. Models considered demographic, socioeconomic, and clinical covariates. False Discovery Rate method controlled risk of error from multiple hypotheses. ResultsAt one month post-completion of treatment, sTNF-RII and IL-6 were elevated by all BC treatments, as were IL-1RA and CRP after surgery alone (all, p < 0.05). By 1 year, markers’ average values returned to baseline. Throughout 2-year follow-up, increase-from-baseline in sTNF-RII, IL-1RA, and IL-6 coincided with worsened Physical Functioning, and increase-from-baseline in sTNF-RII coincided with increased Pain (all, p < 0.01). These biomarker-symptom associations (excepting IL-6) were exclusive to patients. No other symptoms worsened, and baseline Fatigue and Depression improved in all participants. ConclusionsBC treatment, even surgery, is associated with transient elevation in inflammatory markers. In patients post-treatment, increase-from-baseline in sTNF-RII accompanies increased Pain and decreased Physical Functioning, suggesting that sTNF-RII merits development as a clinical biomarker in BC patients.

Exploring the Potential of Drug Repurposing: Detection of Cystic Fibrosis Transmembrane Conductance Regulator as a Biomarker in Breast Cancer Patients

Despite the advancements in cancer treatment and the benefits of personalized medicine, breast cancer (BC) remains a significant health concern. Moreover, conventional treatment options are costly and often associated with severe side effects, highlighting the need to identify new biomarkers and innovative treatment strategies for BC. Drug repurposing presents an approach that expands the therapeutic window further to mitigate the financial burden and minimize the potential harm caused by existing anticancer drugs. In the present study, we aim to suggest noncancerous FDA-approved drugs for repurposing, through molecular docking studies in BC, after their target cystic fibrosis transmembrane conductance regulator protein (CFTR) detection in BC. We used a drug repurposing approach to identify the target protein CFTR and drugs that target CFTR. MOE (molecular operating environment) was used to analyze the interaction between CFTR and its targeting drugs. For experimental work, we did Immunofluorescence staining on BC tissue. We found that glyburide and tezacaftor were the top antagonist and agonists, respectively. We detected CFTR expression in all ten samples except Triple-Negative Breast Cancer (TNBC). CFTR and estrogen receptor alpha co-expressed at 6.78%, suggesting a potential relationship. High-grade tumors showed CFTR expression below 8%, indicating CFTR down-regulation and its role in tumor aggressiveness. Our study is a preliminary step towards in-vitro and in-vivo experiments on repurposing CFTR-targeting drugs in BC. Glyburide may inhibit CFTR's estrogen production, while tezacaftor can enhance CFTR action to overcome tumor aggressiveness.

Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.

The study aimed to analyze the influence of chemotherapy on health biomarkers and examine the relationship between phase angle (PhA) and oxidative stress. A prospective study was performed. Women who were starting chemotherapy were recruited. Also, this study included a control group of women without cancer. Bioelectrical impedance multiple-frequency (BIS) analysis, 24h food recall, and blood samples were collected at 2-time points: diagnosis (T0) and after one month of completion of therapy (T1) for the main study group and one-time point for the control group. T-tests or Mann-Whitney Wilcoxon Test was used to compare variables. Linear regression analysis was conducted to test if PhA is related to the dependent variables after adjusting for age and body mass index. 119 women were included (61 with breast cancer and 58 healthy). There was no difference between the groups concerning anthropometrics, fat mass, and fat-free mass. Breast cancer patients had a worsening in PhA (p<0.001) after chemotherapy completion. PhA was positive statistically correlated with extracellular water, albumin, and the antioxidant markers at both times. The linear model showed that PhA was significantly predicted by C reactive protein, 2,2-Diphenyl-1-picrylhydrazyl (DPPH), Malondialdehyde (MDA), total body water/extracellular water, and body mass index fat mass. This model explained 58% of PhA variability (p<0.001). Our findings show that PhA is an easy and affordable tool that correlates oxidative stress markers in breast cancer patients, regardless of age or body mass index.

MiRNA-1246, HOTAIR, and IL-39 signature as potential diagnostic biomarkers in breast cancer.

The molecular alterations in noncoding RNA can lead to a cellular storm that is correlated to higher mortality and morbidity rates and contributes to the progression and metastasis of cancer. Herein, we aim to evaluate the expression levels and correlations of microRNA-1246 (miR-1246), HOX transcript antisense RNA (HOTAIR), and interleukin-39 (IL-39) in patients with breast cancer (BC). In this study, 130 participants were recruited, including 90 breast cancer patients and 40 healthy control participants. Serum levels of miR-1246 and HOTAIR expression were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Also, the level of IL-39 expression was evaluated using a Western blot. All BC participants demonstrated a remarkable elevation in miR-1246 and HOTAIR expression levels. Moreover, IL-39 expression levels demonstrated a noticeable decline in BC patients. Furthermore, the differential expression fold of miR-1246 and HOTAIR revealed a strong positive correlation among breast cancer patients. In addition, a negative relationship between the IL-39 and the miR-1246 and HOTAIR differential expression was also noticed. This study revealed that HOTAIR/miR-1246 exerts an oncogenic impact in patients with breast cancer. The expression levels of circulation miR-1246, HOTAIR, and IL-39 could be considered early diagnostic biomarkers in BC patients.

Are dietary and serum advanced glycation end-products related to inflammation and oxidation biomarkers in breast cancer patients: a follow-up study.

This study is aimed at evaluating the relationship between dietary and serum advanced glycation end-products (AGEs) with serum inflammatory and oxidative stress biomarkers in breast cancer (BC). A sample of BC patients was followed for 12 months (March 2020-January 2022). Three-day food consumption record and serum samples were taken before surgery (T1), before chemotherapy (T2), at the 6th month of chemotherapy (T3), and at the 12th month of chemotherapy (T4). Dietary AGE intake was represented by carboxymethyl lysine (dCML). Serum levels of CML, inflammation, and oxidation biomarkers were determined with biochemical blood tests. The results were compared according to human epidermal growth factor receptor-2 (HER2) status. Thirty-two women with BC and 32 age and body mass index-matched healthy women participated. No significant correlation was found between dCML and serum CML, inflammatory or oxidative stress biomarkers at T1, T2, and T4. A weak positive correlation was demonstrated between dCML and serum malondialdehyde levels (rho=0.355, p=0.046) at T3. The serum CML, inflammation, and oxidation biomarker levels of the HER2- group were significantly higher than those of the HER2+ group at T1. This study suggests that there is limited correlation between dCML and serum inflammation and oxidative stress biomarkers in BC patients. Inflammation and oxidative biomarker levels appear to decline with treatment although dietary and serum AGE levels show not a corresponding significant decline. The HER2- subtype appears to be associated with higher dietary and serum AGEs and higher inflammatory and oxidative stress biomarkers.

Evaluation of role of serum prolactin &amp; ki-67 in different stages of breast cancer

Breast cancer is the most frequent cancer among women. Prolactin (PRL) is a hormone secreted from anterior pituitary gland which stimulates cell proliferation, survival of cancer cells, its migration, invasion and angiogenesis. Breast cancer is strongly associated with raised plasma Prolactin level (PRL). The Prolactin behaves like Growth Hormone and its actions by the growth-promoting JAK/STAT pathway suggests its tumor-promoting effects.Ki-67 a Nuclear Protein is highest in Luminal B, Ki67 are not related to age but is correlated with tumor size. Fraction of Ki-67 positive tumor cells correlates with the clinical course of cancer cells. Hence, Ki- 67 can be an effective target in cancer therapy. Ki-67% and Serum Prolactin level may be considered a valuable biomarker in breast cancer patients and be used in treatment, follow-up and Prognosis.

Neurotrophin-3 (NT-3) as a Potential Biomarker of the Peripheral Nervous System Damage Following Breast Cancer Treatment

Damage to the peripheral nervous system (PNS) is a common complication of breast cancer (BC) treatment, with 60 to 80% of breast cancer survivors experiencing symptoms of PNS damage. In the current study, the levels of brain-derived neurotrophic factor (BDNF), galectin-3 (Gal-3), and neurotrophin-3 (NT-3) were measured in the blood serum of BC patients by ELISA as potential biomarkers that might indicate the PNS damage. Sixty-seven patients were enrolled in this multi-center trial and compared to the aged-matched healthy female volunteers (control group) (n = 25). Intergroup comparison of biomarker levels (i.e., Gal-3 and BDNF) did not show significant differences in any of the studied subgroups. However, intriguingly, NT-3 levels were significantly higher in BC patients as compared to healthy volunteers, constituting 14.85 [10.3; 18.0] and 5.74 [4.56; 13.7] pg/mL, respectively (p < 0.001). In conclusion, NT-3 might be employed as a potential biomarker in BC patients with clinical manifestations of PNS damage. However, further studies to validate its correlation to the degree of peripheral nervous system lesions are of high value.

Peripheral blood mononuclear cell derived biomarker detection using eXplainable Artificial Intelligence (XAI) provides better diagnosis of breast cancer

The incidence and mortality rate of breast cancer increases yearly by an average of 1.44 % and 0.23 %, respectively. Till 2021, there were 7.8 million women who had been diagnosed with breast cancer within 5 years. Biopsies of tumors are often expensive and invasive and raise the risk of serious complications like infection, excessive bleeding, and puncture damage to nearby tissues and organs. Early detection biomarkers are often variably expressed in different patients and may even be below the detection level at an early stage. Hence PBMC that shows alteration in gene profile as a result of interaction with tumor antigens may serve as a better early detection biomarker. Also, such alterations in immune gene profile in PBMCs are more prone to detection despite variability in different breast cancer mutants.This study aimed to identify potential diagnostic biomarkers for breast cancer using eXplainable Artificial Intelligence (XAI) on XGBoost machine learning (ML) models trained on a binary classification dataset containing the expression data of PBMCs from 252 breast cancer patients and 194 healthy women.After effectively adding SHAP values further into the XGBoost model, ten important genes related to breast cancer development were discovered to be effective potential biomarkers. Our studies showed that SVIP, BEND3, MDGA2, LEF1-AS1, PRM1, TEX14, MZB1, TMIGD2, KIT, and FKBP7 are key genes that impact model prediction. These genes may serve as early, non-invasive diagnostic and prognostic biomarkers for breast cancer patients.

Immune microenvironment and clinical feature analyses based on a prognostic model in lymph node-positive breast cancer.

If lymph node metastasis occurs in breast cancer patients, the disease can progress rapidly. Based on the infiltrative immune cells of breast cancer patients with lymph node positivity, we constructed the LNPRS for selecting prognostic predictors. The LNPRS was established and the predictive value of the LNPRS was verified by independent testing cohorts. A nomogram was also established to confirm the therapeutic guidance significance of the LNPRS. The correlation of the LNPRS with tumor mutation burden, immune microenvironment score, immune checkpoints, the proportion of tumor-infiltrating immune cells, and GSEA and GSVA enrichment pathways were also evaluated. In the training cohort, the overall survival of breast cancer patients who had high LNPRS was shorter than that of patients who had low LNPRS (7.98 years versus 20.42 years, P-value< 8.16E-11). The AUC values for 5-, 10-, and 15-years were 0.787, 0.739, and 0.800, respectively. The ability to predict prognosis for the LNPRS was also tested in 3 independent testing cohorts. Furthermore, the predictive value of the LNPRS for chemotherapy and immunotherapy was also proven. The GSEA and GSVA showed that the LNPRS was closely related to the activation of T and B lymphocytes and IFN-γ secretion. Moreover, breast cancer patients with low LNPRS had higher TME scores than those with high LNPRS. We can conclude that the LNPRS is a robust prognostic biomarker in breast cancer patients with positive lymph nodes and may be helpful for patients to make a clinical decision.

Abstract P2-16-02: TXNIP-dependent tumor suppressive pathways in breast cancer growth and progression

Abstract Thioredoxin-interacting protein (TXNIP) plays a critical role in glucose metabolism and redox signaling through negatively regulating thioredoxin activity. Over the past decade, TXNIP has emerged as a novel tumor suppressor in various cancer models. In search of the molecular targets mediating the anticancer effect of an epigenetic drug UNC0642, we found TXNIP to be consistently upregulated by UNC0642, which was coupled with significant suppression of MDA-MB-231 breast cancer cell proliferation in vitro and tumor growth in vivo. TXNIP knockdown increased MDA-MB-231 cell proliferation and in vivo tumor growth and metastasis. In contrast, TXNIP-reconstitution in TXNIP-deficient HCC1954 breast cancer cells suppressed cell proliferation and migration that is coupled with increases in reactive oxygen species, strongly supporting TXNIP’s potent antitumor function. TXNIP-reconstitution also decreased mitochondrial respiration and glycolysis in HCC-1954 cells as determined by using the Agilent Seahorse XF Cell Energy assays. To understand the molecular targets through which TXNIP exerted its antitumor activity, we performed co-immunoprecipitation studies and proteomic analyses to identify TXNIP-interacting proteins in UNC0642-treated MDA-MB-231 cells. Besides thioredoxin, we identified peroxiredoxin-6 (PRDX6), another modulator of cellular redox signaling, as a major TXNIP-interacting protein. While Prdx6-knockout mice develop normally, PRDX6 is frequently upregulated in breast cancer patients that is significantly associated with aggressive tumor subtypes and poor overall survival. The mechanism underlying the role of PRDX6 in breast oncogenesis remains elusive. Our findings suggest that TXNIP might exert its antitumor activity through binding and inhibiting PRDX6 activity in breast cancer cells to alter ROS signaling, thus providing novel therapeutic targets and potential prognostic biomarkers for breast cancer patients. Citation Format: Jasvinder Singh, Bindeshwar sah, Liang Liu. TXNIP-dependent tumor suppressive pathways in breast cancer growth and progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-16-02.

Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis.

Background: Breast cancer (BC) is the most common cancer in women. The incidence and morbidity of BC are expected to rise rapidly. The stage at which BC is diagnosed has a significant impact on clinical outcomes. When detected early, an overall 5-year survival rate of up to 90% is possible. Although numerous studies have been conducted to assess the prognostic and diagnostic values of non-coding RNAs (ncRNAs) in breast cancer, their overall potential remains unclear. In this field of study, there are various systematic reviews and meta-analysis studies that report volumes of data. In this study, we tried to collect all these systematic reviews and meta-analysis studies in order to re-analyze their data without any restriction to breast cancer or non-coding RNA type, to make it as comprehensive as possible. Methods: Three databases, namely, PubMed, Scopus, and Web of Science (WoS), were searched to find any relevant meta-analysis studies. After thoroughly searching, the screening of titles, abstracts, and full-text and the quality of all included studies were assessed using the AMSTAR tool. All the required data including hazard ratios (HRs), sensitivity (SENS), and specificity (SPEC) were extracted for further analysis, and all analyses were carried out using Stata. Results: In the prognostic part, our initial search of three databases produced 10,548 articles, of which 58 studies were included in the current study. We assessed the correlation of non-coding RNA (ncRNA) expression with different survival outcomes in breast cancer patients: overall survival (OS) (HR = 1.521), disease-free survival (DFS) (HR = 1.33), recurrence-free survival (RFS) (HR = 1.66), progression-free survival (PFS) (HR = 1.71), metastasis-free survival (MFS) (HR = 0.90), and disease-specific survival (DSS) (HR = 0.37). After eliminating low-quality studies, the results did not change significantly. In the diagnostic part, 22 articles and 30 datasets were retrieved from 8,453 articles. The quality of all studies was determined. The bivariate and random-effects models were used to assess the diagnostic value of ncRNAs. The overall area under the curve (AUC) of ncRNAs in differentiated patients is 0.88 (SENS: 80% and SPEC: 82%). There was no difference in the potential of single and combined ncRNAs in differentiated BC patients. However, the overall potential of microRNAs (miRNAs) is higher than that of long non-coding RNAs (lncRNAs). No evidence of publication bias was found in the current study. Nine miRNAs, four lncRNAs, and five gene targets showed significant OS and RFS between normal and cancer patients based on pan-cancer data analysis, demonstrating their potential prognostic value. Conclusion: The present umbrella review showed that ncRNAs, including lncRNAs and miRNAs, can be used as prognostic and diagnostic biomarkers for breast cancer patients, regardless of the sample sources, ethnicity of patients, and subtype of breast cancer.

Assessment Of Serum Levels of Zeb2 and Fat10 and Tumor Necrosis Factor-Alpha as Potential Novel Biomarkers in Breast Cancer Patients

Assessment Of Serum Levels of Zeb2 and Fat10 and Tumor Necrosis Factor-Alpha as Potential Novel Biomarkers in Breast Cancer Patients

Small breast epithelial mucin as a useful prognostic marker for breast cancer patients.

This study aimed to evaluate the clinical utility of small breast epithelial mucin (SBEM) as a prognostic biomarker in an independent patient cohort. The paraffin-embedded tissues and clinicopathological data of 105 patients with breast cancer were collected, and the expression of SBEM in breast cancer samples was detected by immunohistochemical staining. The correlations between clinicopathological variables and the expression of SBEM were analyzed, and its significance as a prognostic indicator for breast cancer patients was determined. Immunohistochemical staining revealed that SBEM was expressed mostly in the cytomembrane and cytoplasm, with markedly increased SBEM expression (≥4 points on staining intensity) observed in 34 of 105 breast cancer tissues (32.4%). Elevated expression of SBEM was found to be significantly associated with larger tumor size (P = 0.002), more frequent lymph node metastasis (P = 0.029), advanced tumor node metastasis stage (P = 0.005), reduced expression of the progesterone receptor (PR) (P = 0.002), and a higher Ki-67 index (P = 0.006). Survival analysis indicated that patients with elevated SBEM expression had worse overall survival (OS) (5-year OS rate: 50.5 vs 93.9% for high and low SBEM expression, respectively, P < 0.001) and disease-free survival (DFS) (5-year DFS rate: 52.8 vs 81.7% for high and low SBEM expression, respectively, P = 0.001) rates than those with low expression of SBEM. Univariate and multivariate Cox analyses demonstrated that elevated expression of SBEM (hazard ratio [HR] = 1.994, 95% confidence interval [CI]: 1.008-3.945, P = 0.047), tumor size (HR = 2.318, 95% CI: 1.071-5.017, P = 0.033), and PR status (HR = 0.195, 95% CI: 0.055-0.694, P = 0.012) were independent predictors of OS in breast cancer patients. Elevated expression of SBEM was associated with both aggressive tumor characteristics and poor survival, indicating its potential as a useful prognostic biomarker for breast cancer patients.

Comprehensive Analysis Reveals PTK6 as a Prognostic Biomarker Involved in the Immunosuppressive Microenvironment in Breast Cancer.

The significant mortality rate that is currently experienced by female breast cancer (BC) patients highlights the importance of locating potent and dependable biomarkers in BC patients. Over the past few years, a number of studies have demonstrated that PTK6 was dysregulated in a variety of cancers. However, its expression and the clinical importance it may have in patients with BC have not been explored. Based on datasets from the TCGA database and GTEx database, we studied the expressions and functions of PTK6 across 33 different kinds of cancer. In this study, we investigated the differential expression of PTK6 in tumor tissue compared to nontumor tissue as well as in various stages of cancer. ROC assays were used to conduct an investigation into the diagnostic potential of PTK6 in BC. After that, the Kaplan-Meier method, univariate analysis, and multivariate analysis were carried out in order to investigate the PTK6 gene's potential prognostic significance in patients with BC. ssGSEA was utilized in order to conduct an investigation of the immune infiltration. In this study, we discovered that the expressions of PTK6 were significantly raised in the majority of different types of malignancies, including BC. The diagnostic value of PTK6 expression was validated by ROC tests, demonstrating an AUC greater than 0.7. A positive PR, ER, and HER2 status was found to be related with high expression levels of PTK6. According to the results of a survival analysis, patients who had a high level of PTK6 expression had a shorter overall survival time than those who had a low level of PTK6 expression. Besides, we observed that PTK6 expressions were positively correlated with the abundance of NK CD56bright cells and Th17 cells and negatively correlated with that of Th1 cells, macrophages, B cells, T cells, aDC, DC, cytotoxic cells, Tem, TFH, NK CD56dim cells, Treg, and Tgd. In conclusion, PTK6 expression was found to be linked with the clinical phenotype of BC, and as a result, this finding may have consequences for the diagnosis, prognosis, and treatment of individuals with BC.

Abstract 15460: Comprehensive Diet and Exercise Intervention During Radiation Therapy Can Improve Metabolic and Inflammatory Markers in Breast Cancer Patients

While radiation therapy (RT) is effective for reducing cancer burden in breast cancer (BC) patients, its side effects promote sedentary behavior and accumulation of adipose mass. Obesity and inactivity further increase the risk for cardiovascular co-morbidities and mortality. To combat these effects, we piloted a 12-week Stay on Track (SOT) exercise and diet intervention for breast cancer patients during their RT. We hypothesize that SOT will positively influence body composition and metabolic and inflammatory biomarkers in BC patients. A prospective, randomized control trial for patients with non-metastatic BC undergoing whole-breast RT was conducted. The intervention ( A; 21 patients) group participated in 3 personal excercise training sessions, 3 dietary counseling sessions, and received 3 text message reminders per week to adhere to lifestyle recommendations. The control (B; 22 patients ) group received an informative binder. All patients received a Fitbit, and at baseline, 3months, and 6months, measurements of blood biomarkers and dual-energy x-ray absorptiometry (DXA) scans were conducted. A mixed models analysis with a significance value of 0.05 was conducted, and estimated change from baseline with SE’s are reported. There was trend towards lower BMI (-0.95, 0.49; p=0.06) at 6mo and decreased visceral fat (-2.17, 1.22; p=0.081) at 3mo in A only. B had an increase in HbA1C at 3mo compared to baseline (0.26, 0.10; p=0.01) which stayed elevated at 6mo (0.22, 0.13; p=0.08). B also had an increase in glucose levels at 6mo (8.42, 3.94; p=0.04), with a trend towards a decrease in insulin (-14.30, 9.85; p=0.15). A had no changes in these levels. There was a significant decrease in leptin levels at 6mo in B only (-13583.7, 6184.2, p=0.03). Adiponectin levels trended higher in A compared to B at 6mo (3143.42, 2265.1; p=0.17). Analysis of inflammatory cytokines showed a decrease in anti-inflammatory IL-1R-a in B (-3.46, 1.24; p=0.01), and a reduction in pro-inflammatory IL-8 levels in A (-2.77, 1.15; p=0.02). We conclude that SOT may positively influence body composition and metabolic and inflammatory biomarkers in BC patients. Targeted lifestyle interventions during RT are feasible and could help decrease cardiovascular co-morbidities in BC.

Clinical relevance of CERK and SPHK1 in breast cancer and their association with metastasis and drug resistance

Despite numerous reports on the altered sphingolipids metabolism in human cancers, their clinical significance in breast cancer remains obscure. Previously, we identified the high levels of sphingolipids, ceramide phosphates and sphingosine phosphates, and the genes involved in their synthesis, CERK and SPHK1, in breast cancer patients. The present study aimed to determine the correlations of CERK and SPHK1 with clinical outcomes as well as metastasis and drug resistance markers. Both local and TCGA cohorts were analysed. High-confidence regulatory interaction network was constructed to find association of target genes with metastasis and drug resistance. Furthermore, correlations of CERK and SPHK1 with selected metastasis and drug resistance markers were validated in both cohorts. Overexpression of CERK and SPHK1 was associated with nodal metastasis, late tumor stage and high proliferation potency. In addition, increased CERK expression was also indicative of poor patient survival. Computational network analysis revealed the association of CERK and SPHK1 with known metastasis markers MMP-2 and MMP-9 and drug resistance markers ABCC1 and ABCG2. Correlation analysis confirmed the associations of target genes with these markers in both local as well as TCGA cohort. The above findings suggest clinical utility of CERK and SPHK1 as potential biomarkers in breast cancer patients and thus could provide novel leads in the development of therapeutics.

Prognostic Potential of Immune Inflammatory Biomarkers in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Immune inflammatory biomarkers are easily obtained and inexpensive blood-based parameters that recently showed prognostic and predictive value in many solid tumors. In this study, we aimed to investigate the role of these biomarkers in predicting distant relapse in breast cancer patients treated with neoadjuvant chemotherapy (NACT). All breast cancer patients who referred to our Breast Unit and underwent NACT were retrospectively reviewed. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were calculated from complete blood counts. The primary outcome was 5-year distant-metastasis-free survival (DMFS). In receiver operating characteristic analyses, the optimal cutoff values for the NLR, PLR, MLR, and PIV were determined at 2.25, 152.46, 0.25, and 438.68, respectively. High levels of the MLR, but not the NLR, PLR, or PIV, were associated with improved 5-year DMSF in the study population using both univariate (HR 0.52, p = 0.03) and multivariate analyses (HR, 0.44; p = 0.02). Our study showed that the MLR was a significant independent parameter affecting DMFS in breast cancer patients undergoing NACT. Prospective studies are required to confirm this finding and to define reliable cutoff values, thus leading the way for the clinical application of this biomarker.

Correlation of TBK1, AR, and other serum cancer-related biomarkers in breast cancer patients: An observational study.

Breast cancer (BC) ranks first for incidence and mortality in gynecological malignant tumors. This study aims to investigate the diagnostic value of Tank-binding kinase 1 (TBK1) and its correlation with androgen receptor (AR) and other serum cancer-related biomarkers in BC patient. The present observational study included 451 female BC patients and 451 healthy controls. Serum levels of TBK1, AR and other cancer-related biomarkers were detected in all the patients and healthy controls. Patients’ demographic data and clinical data including age, body mass index (BMI), tumor node Metastasis (TNM), pathological type, tumor size and lymph node metastasis were collected. The follow-up lasted for 5 years.The deceased group had higher rate of patients with TNM III~IV, lymph node metastasis or tumor diameter >2. Deceased group had much higher rate of patients with negative ER and positive Ki67. Besides, increased TBK1 was found in BC patients with positive correlation with AR, CA15-3, CA125, CEA, and CA19-9. Serum TBK1 was associated with the clinic outcomes of BC patients and those with high TBK1 had lower 5-year survival rate. Moreover, cutoff value of 13.95 ng/mL TBK1 showed AUC of 0.981 (93.6% for sensitivity and 86.3% for specificity) for diagnosing BC, and cutoff value of 22.65 ng/mL TBK1 had AUC of 0.996 (97.7% for sensitivity and 96.3% for specificity) for diagnosing the death of BC patients. Serum TBK1 was positively correlated with AR and other serum cancer-related biomarkers. In addition, high TBK1 predicted the poor prognosis and might be used for the diagnosis of BC.

Novel lncRNAs with diagnostic or prognostic value screened out from breast cancer via bioinformatics analyses.

BackgroundRecent studies have shown that long non-coding RNAs (lncRNAs) may play key regulatory roles in many malignant tumors. This study investigated the use of novel lncRNA biomarkers in the diagnosis and prognosis of breast cancer.Materials and MethodsThe database subsets of The Cancer Genome Atlas (TCGA) by RNA-seq for comparing analysis of tissue samples between breast cancer and normal control groups were downloaded. Additionally, anticoagulant peripheral blood samples were collected and used in this cohort study. The extracellular vesicles (EVs) from the plasma were extracted and sequenced, then analyzed to determine the expressive profiles of the lncRNAs, and the cancer-related differentially expressed lncRNAs were screened out. The expressive profiles and associated downstream-mRNAs were assessed using bioinformatics (such as weighted correlation network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichments, Receiver-Operating Characteristic (ROC) curve and survival analysis, etc.) to investigate the diagnostic and prognostic values of these EV lncRNAs and their effectors.ResultsIn this study, 41 breast cancer-related lncRNAs were screen out from two datasets of tissue and fresh collected plasma samples of breast cancer via the transcriptomic and bioinformatics techniques. A total of 19 gene modules were identified with WGCNA analysis, of which five modules were significantly correlated with the clinical stage of breast cancer, including 28 lncRNA candidates. The ROC curves of these lncRNAs revealed that the area under the curve (AUC) of all candidates were great than 70%. However, eight lncRNAs had an AUC >70%, indicating that the combined one has a good diagnostic value. In addition, the results of survival analysis suggested that two lncRNAs with low expressive levels may indicate the poor prognosis of breast cancer. By tissue sample verification, C15orf54, AL157935.1, LINC01117, and SNHG3 were determined to have good diagnostic ability in breast cancer lesions, however, there was no significant difference in the plasma EVs of patients. Moreover, survival analysis data also showed that AL355974.2 may serve as an independent prognostic factor and as a protective factor.ConclusionA total of five lncRNAs found in this study could be developed as biomarkers for breast cancer patients, including four diagnostic markers (C15orf54, AL157935.1, LINC01117, and SNHG3) and a potential prognostic marker (AL355974.2).

Angiogenic activities of interleukin-8, vascular endothelial growth factor and matrix metalloproteinase-9 in breast cancer

Angiogenesis is a major contributor to tumor growth and metastasis within breast cancer tumor microenvironment in which different proangiogenic factors have been identified and associated with tumor progression, metastasis and poor prognosis. The aim of the current study was to evaluate the angiogenesis among breast cancer patients through ex vivo assessment of the angiogenic factors interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF)-A expressions in excised tumor tissues as well as matrix metalloproteinase 9 (MMP-9) serum levels as well as the prognostic value of MMP-9. Our study included 28 invasive ductal carcinoma female patients who were scheduled for modified radical mastectomy at Medical Research Institute, Alexandria University, Egypt and 10 control subjects. Both IL-8 and VEGF-A expressions were immunohistochemically detected in tumor tissues and serum MMP-9 was determined by ELISA. Although no significant correlations were found between each of IL-8, VEGF-A, MMP-9 levels, and patients' clinicopathological parameters, a significant positive correlation was found between these angiogenic factors each other suggesting their synergistic roles in proceeding angiogenesis. Higher serum MMP-9 level was detected in breast cancer patients compared to the control group, indicating that it can be used as a prognostic biomarker in breast cancer patients.