Marker In Breast Cancer Research Articles

IF-7 and GALA modified PEG-PDMAEMA loaded SOX10 siRNA nanoparticles: Preparation, cellular delivery, and inhibition on progression of triple negative breast cancer and its bone metastasis in vitro

SRY-related high-mobility-group box 10 (SOX10) is reported to be a sensitive lineage marker in primary and metastatic triple negative breast cancer (TNBC). However, there has no exploration in the delivery of SOX10 small interfering RNA (siRNA) to treat TNBC. Poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PDMAEMA) modified with peptides IF-7 and GALA was employed to assemble SOX10 siRNA into nanoparticles. The results revealed that the prepared nanoparticles were was regularly round with uniform sizes of about 102.9 ± 1.93 nm, exhibiting good stability and pH-triggered release profile at pH 5.0. The nanoparticles were efficiently uptaken by MDA-MB-231 cells via cholesterol dependent, caveolae- and clathrin-mediated endocytosis and escaped from lysosomes. The nanoparticles inhibited proliferation, invasion and migration of MDA-MB-231 cells, as well as chemotactic migration, heterogeneous adhesion and anchorage-independent growth of MDA-MB-231 cells in simulated bone microenvironment. The nanoparticles inhibited the mRNA and protein expression of SOX10, subsequently inhibited Nestin, β-catenin, c-Myc and CyclinD1 expression. The effect of the nanoparticles on TNBC and its bone metastasis might attribute to the blockade of Nestin and Wnt/β-catenin pathway after the silencing of SOX10. Taken together, IF-7 and GALA modified PEG-PDMAEMA loaded SOX10 siRNA nanoparticles provide a new strategy to treat TNBC and its bone metastasis.

FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).

While preclinical studies consistently implicate FGFR‑signalling in breast cancer (BC) progression, clinical evidence fails to support these findings. It may be that the clinical significance of FGFR ought to be analysed in the context of the stroma, activating or repressing its function. The present review aimed to provide such a context by summarizing the existing data on the prognostic and/or predictive value of selected cancer‑associated fibroblasts (CAFs)‑related factors, that either directly or indirectly may affect FGFR‑signalling. PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Medline (https://www.nlm.nih.gov/medline/medline_home.html) databases were searched for the relevant literature related to the prognostic and/or predictive significance of: CAFs phenotypic markers (αSMA, S100A4/FSP‑1, PDGFR, PDPN and FAP), CAFs‑derived cognate FGFR ligands (FGF2, FGF5 and FGF17) or inducers of CAFs' paracrine activity (TGF‑β1, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF) both expressed in the tumour and circulating in the blood. A total of 68 articles were selected and thoroughly analysed. The findings consistently identified upregulation of αSMA, S100A4/FSP‑1, PDGFR, PDPN, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF as poor prognostic markers in BC, while evaluation of the prognostic value of the remaining markers varied between the studies. The data confirm an association of CAFs‑specific features with BC prognosis, suggesting that both quantitative and qualitative profiling of the stroma might be required for an assessment of the true FGFR's clinical value.

Identification of the novel exhausted T cell CD8 + markers in breast cancer

Cancer is one of the most concerning public health issues and breast cancer is one of the most common cancers in the world. The immune cells within the tumor microenvironment regulate cancer development. In this study, single immune cell data sets were used to identify marker gene sets for exhausted CD8 + T cells (CD8Tex) in breast cancer. Machine learning methods were used to cluster subtypes and establish the prognostic models with breast cancer bulk data using the gene sets to evaluate the impacts of CD8Tex. We analyzed breast cancer overexpressing and survival-associated marker genes and identified CD8Tex hub genes in the protein–protein-interaction network. The relevance of the hub genes for CD8 + T-cells in breast cancer was evaluated. The clinical associations of the hub genes were analyzed using bulk sequencing data and spatial sequencing data. The pan-cancer expression, survival, and immune association of the hub genes were analyzed. We identified biomarker gene sets for CD8Tex in breast cancer. CD8Tex-based subtyping systems and prognostic models performed well in the separation of patients with different immune relevance and survival. CRTAM, CLEC2D, and KLRB1 were identified as CD8Tex hub genes and were demonstrated to have potential clinical relevance and immune therapy impact. This study provides a unique view of the critical CD8Tex hub genes for cancer immune therapy.

Expression profile and functional analysis of miR-301b in patients with breast cancer: A bioinformatics, biochemical, and histopathological study

BackgroundmicroRNAs (miRNAs) are crucial regulators of various biological processes and molecular functions. Aberrant miRNA expression has been linked in many studies to neoplastic transformation. Among these miRNAs, dysregulation of miR-301b-5p was associated with different types of cancer including breast cancer. Although many research works have investigated the function of miR-301b in carcinogenesis, few have examined its expression, biological, and clinical implications in breast cancer. Methodswe examined the expression levels of miR-301b-5p in human cancerous breast tissue compared to normal breast controls using different bioinformatic tools and RT-qPCR analyses. Resultswe detected that miR-301b-5p was differentially expressed in cancerous breast tissue when compared to normal controls. MiR-301b-5p was detected to be upregulated in high-grade (Grade 3) and triple-negative breast cancers. A significant strong positive correlation was detected between miR-301b and Ki-67, the commonly used proliferative marker in breast cancer. Bioinformatics analyses using the KM plotter revealed that miR-301b has significant prognostic power in assessing the OS of patients with breast cancer. The study also identified many fundamental biological processes and regulatory pathways associated with the investigated miR-301b-related hub genes. Interestingly, the expression pattern and prognostic significance of PTEN, the top hub gene regulated by miR-301b, highlighted the prognostic significance of PTEN in breast cancer. ConclusionThe current study findings suggest the potential use of miR-301b-5p as a possible diagnostic and prognostic biomarker in breast cancer. Moreover, this study emphasized the clinical and biological relevance of miR-301b-5p in breast cancer.

Role of MicroRNA-204 in Regulating the Hallmarks of Breast Cancer: An Update.

microRNA-204-5p (miR-204) is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC, known as the hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, β-catenin, VEGFA, TGFBR2, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior.

Potential-Resolved Ratio Electrochemiluminescence Biosensor Based on Perylene Diimide-MOF and DNA Nanoflowers-CdS Quantum Dots for Detection of Dual Targets.

BRCA1 gene and carcinoembryonic antigen (CEA) are important markers of breast cancer, so accurate detection of them is significant for early detection and diagnosis of breast cancer. In this study, a potential-resolved ratio electrochemiluminescence (ECL) biosensor using perylene diimide (PDI)-metal-organic framework and DNA nanoflowers (NFs)-CdS quantum dots (QDs) was constructed for detection of BRCA1 and CEA. Specifically, PDI-MOF and CdS QDs can generate potential-resolved intense ECL signals only using one coreactant, so the detection procedure can be effectively simplified. PDI-MOF was first attached to the electrode by graphene oxide, and the dopamine (DA) probe was linked to quench the ECL signal by DNA hybridization. In the presence of target BRCA1, it can form a bipedal DNA walker, so the quenching molecules (DA) were detached from the electrode via the walker amplification process aided by Mg2+, so that the PDI signal at -0.25 V was restored for the BRCA1 assay. Moreover, CdS QDs@DNA NFs as amplified signal probes were formed by self-assembly, and the target CEA-amplified product introduced the CdS QDs@DNA NFs to the electrode, so the QD ECL signal at -1.42 V was enhanced, while the ECL signal of PDI is unchanged; thus, CEA detection was achieved by the ratio value between them. Therefore, the detection accuracy is guaranteed by detection of two cancer markers and a ratio value. This biosensor has a great contribution to the development of new ECL materials and a novel ECL technique for fast and efficient multitarget assays, showing great significance for the early monitoring and diagnosis of breast cancer.

Characterization of SUSD3 as a novel prognostic biomarker and therapeutic target for breast cancer.

Breast cancer (BC) remains a significant global health challenge, contributing substantially to cancer-related deaths worldwide. Its prevalence and associated death rates remain alarmingly high, highlighting the persistent public health burden. The objective of this study was to systematically examine the involvement of SUSD3 (Sushi Domain-Containing 3) in BC, highlighting its crucial role in the pathogenesis and progression of this disease. BC-related gene microarray data, along with corresponding clinicopathological information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Leveraging TIMER and HPA databases, we conducted comparative analyses to evaluate SUSD3 expression in BC. We then analyzed the association between SUSD3 and clinical traits, as well as the prognostic value of SUSD3. SUSD3-related differential expression genes (DEGs) were sent for analysis utilizing GO, KEGG, and GSEA. We utilized SUSD3 mRNA expression to assess immune cells' scores in BC tissues calculated by single-sample enrichment analyses based on "CIBERSORT" R package. Drug sensitivity analysis was used to screen potential drugs sensitive to SUSD3. R software was used for statistical analyses and graphical representation of the data. Our findings confirmed a significant upregulation of SUSD3 expression in BC, which correlated with a favorable prognosis. Clinical correlation analysis further emphasized the strong association between SUSD3 expression and key clinical parameters like estrogen receptor (ER) status, progesterone receptor (PR) status, stage, and T classification in breast cancer. Univariate and multivariate Cox regression analyses showed that SUSD3 could be used as an independent prognostic factor for BC. Differentially expressed genes (DEGs) co-expressed with SUSD3 were significantly associated with various biological processes, such as the cell cycle, DNA replication, p53 signaling pathway, cancer-related pathways, and Wnt signaling pathway, as indicated by gene set enrichment analysis (GSEA). Furthermore, our analysis demonstrated that SUSD3 generally exhibited negative associations with immune modulators. Drug sensitivity analysis revealed positive correlations between SUSD3 and the efficacy of Fulvestrant, Raloxifene, and Fluphenazine. The research emphasizes the significance of SUSD3 as a potential marker for BC, providing insights into the underlying molecular mechanisms implicated in tumorigenesis. SUSD3 holds promise in helping the classification of breast cancer pathological groups, predicting prognosis, and facilitating targeted therapy.

Hybrid Adaptive Threshold Segmentation for predicting Breast Cancer

Breast cancer is a leading cause of death for women in many parts of the world. The disease is often misdiagnosed until it has progressed beyond the point of effective treatment. Therefore, early detection of the disease would aid in reducing mortality and other associated risks. Microarray gene expression data is difficult to identify and interpret, making it challenging to evaluate and choose the most relevant set of genes for use as breast cancer markers. Our research utilized Matlab 2018a and the Breast Cancer Wisconsin Diagnostic dataset to develop a mixed machine-learning model for fast breast cancer prediction. Here, we apply various machine learning techniques including random forest classification, logistic regression, support vector machine and Naive Bayes, as well as to a dataset to make predictions about their development and eventual size. The success percentage for the eXtreme Gradient Boosting classifier compared to various machine learning approaches is 99.78%. This new approach to prediction has the potential to revolutionize the detection, analysis and prognosis of breast cancer.

FGF-21 Level is higher in patients with breast cancer, a candidate for a new biomarker?

Aims: Fibroblast Growth Factor 21 (FGF-21) is a member of the FGF family involved in biological processes such as embryonic development. cell growth. morphogenesis. tissue repair. tumour growth and invasion. with mitogenic and cytogenetic activity at 19q13.33.Breast cancer is a deadly and increasing disease in women. and recent studies have shown a relationship between some cancers. including breast cancer. and hormones secreted from adipose tissue.The aim of the present study was the measurement of FGF-21 levels in patients with breast cancer and its association with breast cancer. Methods: The study included 39 patients with newly diagnosed breast cancer and 39 healthy controls. During the patients’ routine blood tests. a venous blood sample was taken and the serum levels of FGF-21 were determined by ELISA. Results: Demographic and laboratory data were compared between the newly diagnosed breast cancer group and the control group. The control group consisted of 39 participants with a mean age of 52.49 ± 7.02 years. In the patient group. 39 participants with a mean age of 52.15 ± 6.21 years were included in the study. there was no statistical difference regarding age(p>0.05).In the control group. the mean FGF-21 level was 121.35 ± 88.4 pg/ml. while the mean FGF-21 level in the patient group was 171 ± 117.45 pg/ml. a statistically significant difference was detected(p value=0.036). Conclusion: FGF-21 is thought to have significant and beneficial effects on glucose. lipid and energy metabolism. as well as slowing the growth of cancer cells. and may later be used as a biological marker for breast cancer.

Unveiling heterogeneity and prognostic markers in ductal breast cancer through single-cell RNA-seq

BackgroundBreast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets.MethodsBioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes.ResultsThe analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells.ConclusionThis study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Exploring SALL4 as a significant prognostic marker in breast cancer and its association with progression pathways involved in cancer genesis

Breast carcinoma is the leading factor in women's cancer-related fatalities. Due to its numerous inherent molecular subtypes, breast cancer is an extremely diverse illness. The human epidermal growth factor receptor 2 (HER2) positive subtypes stands out among these subtypes as being especially prone to cancer development and illness recurrence. The regulation of embryonic stem cells' pluripotency and self-renewal is carried out by the SALL4 (Spalt-like transcription factor 4) family member. Numerous molecular pathways operating at the transcriptional, post-transcriptional, and epigenomic levels regulate the expression of SALL4. Many transcription factors control the expression of SALL4, with STAT3 being the primary regulator in hepatocellular carcinoma (HCC) and breast carcinoma. Moreover, this oncogene has been connected to a number of cellular functions, including invasion, apoptosis, proliferation, and resistance to therapy. Reduced patient survival rates and a worse prognosis have been linked to higher levels of SALL4. In order to target the undruggable SALL4 that is overexpressed in breast carcinoma, we investigated the prognostic levels of SALL4 in breast carcinoma and its interaction with various related proteins. Using TIMER 2.0 analysis, the expression pattern of SALL4 was investigated across all TCGA datasets. The research revealed that SALL4 expression was elevated in various cancers. The UALCAN findings demonstrated that SALL4 was overexpressed in all tumor samples including breast cancer especially TNBC (Triple negative breast cancer). The web-based ENRICHR program was used for gene ontology analysis that revealed SALL4 was actively involved in the development of the nervous system, positive regulation of stem cell proliferation, regulation of stem cell proliferation, regulation of the activin receptor signaling pathway, regulation of transcription using DNA templates, miRNA metabolic processes, and regulation of transcription by RNA Polymerase I. Using the STRING database, we analyzed the interaction and involvement of SALL4 with other abruptly activated proteins and used Cytoscape 3.8.0 for visualization. Additionally, using bc-GenExMiner, we studied the impact of SALL4 on pathways abruptly activated in different breast cancer subtypes that revealed SALL4 was highly correlated with WNT2B, NOTCH4, AKT3, and PIK3CA. Furthermore, to target SALL4, we evaluated and analyzed the impact of CLP and its analogues, revealing promising outcomes.

The influence of polymorphism of genes associated with breast cancer on the effectiveness of drug antitumor therapy

Background. Increasing the survival rate of breast cancer patients is a problem all over the world and directly depends on the early detection of a malignant tumor. Genome-wide associative studies (GWAS) as a minimally invasive method may be used in determining risk of breast cancer or detection at an early stage. The increase in the number of patients with disseminated breast cancer in the Republic of Kazakhstan makes it necessary to search for molecular genetic markers of breast cancer for their use in the diagnosis and treatment of patients with this pathology.Aim. To retrospectively estimate the correlation of the effectiveness of drug antitumor therapy for breast cancer with gene polymorphism.Materials and methods. The study included the results of genotyping biomaterial samples on high-density DNA chips (venous blood of 1,277 Kazakh patients (in the third generation) with a verified diagnosis of breast cancer with locally advanced and disseminated breast cancer who received anticancer therapy), clinical data of patients, data on the clinical efficacy and toxicity of drug therapy. GWAS data (genotypes) associated with identified responses to chemotherapy drugs were compared with similar data recorded in international databases.Results. The family history study showed 16.52 % of women in the questionnaires had a family history of various types of ESR, and 86.25 % of them had a burden of breast cancer in women of the first degree of kinship. The average age of patients with breast cancer was 48.79 ± 11.44 years. According to the TNM classification, cancer in situ was detected in 4.78 % of patients, stage I of the disease was recorded in 15.27 %, stage II in 63.43 %, stage III in 12.60 %, stage IV in 3.92 % of patients. The vast majority of the patients (96.9 %) had a nodular form of breast cancer. The distribution of the patients by tumor phenotype: luminal type A was found in 20.4 % of patients, luminal type B in 38.3 %, luminal type B with HER2 overexpression in 14.3 %, HER2 positive form in 11.9 % of cases, 12.4 % of patients had an aggressive form – triple negative breast cancer. 18 main genotypes were identified in the Kazakh population as a result of the analysis of associations of the effectiveness of neoadjuvant chemotherapy (its individual components, according to chemotherapy regimens) and individual gene polymorphisms.Conclusion. An associative relationship between different types of gene polymorphism and the characteristics of response to various chemotherapeutic drugs used in the treatment of breast cancer has been confirmed. The obtained results formed the basis for the development of recommendations for making changes to the clinical practice of the Republic of Kazakhstan in order to use them in identifying a genetic predisposition to breast cancer and the effectiveness of drugs used in treatment.

An electrochemical biosensor with enhanced antifouling properties enabled by peptide self-assembly via robust Pt-S interactions

Designing effective biosensing interfaces requires robust biomolecule immobilization strategies. Traditional gold-sulfur bonds (Au-S) have low affinity and are prone to ligand substitution reactions in complex biological environments. In this study, we introduce an innovative approach utilizing a trifunctional branched-cyclopeptide (TBCP) for self-assembly onto platinum nanoparticles (PtNP)-modified electrodes. TBCP immobilization on PtNP via Pt-S interaction proves significantly more stable than Au-S bonding. In addition, TBCP peptides assembled through Pt-S interactions exhibit low susceptibility to displacement by small molecules like glutathione, making them ideal for constructing robust biosensors with high stability in biological fluids. Leveraging peptide multifunctionality and strong Pt-S interactions, TBCP-modified electrodes excel in various biological fluids, detecting the breast cancer marker ErbB2 in human serum. The high sensitivity of the TBCP/PtNP-based biosensor distinguishes serum samples from breast cancer patients and healthy individuals. This self-assembly strategy represents a promising advance in constructing biosensors with robust operation in complex biological media.

Circulating tumor DNA in Egyptian women with breast Cancer: A marker for detection of primary cases and early prediction of recurrence

Worldwide, female breast cancer (BC) has surpassed lung cancer as the most commonly diagnosed cancer. Early diagnosis of cancer recurrence can provide substantial benefits for BC patients who are at high risk of relapse. We aimed to investigate the role of ALU 247, ALU 115, cfDNA integrity index, CA15-3 and CEA as potential diagnostic markers in BC patients and as markers for early prediction of recurrence. Fifty BC patients (10 patients showed recurrence), 26 BBD patients and 22 healthy controls were included. Real-time q-PCR was used to measure the concentration of ALU 247 and ALU 115 in plasma then cfDNA integrity index was calculated. “ECLIA” was used to measure the concentration of CA15-3 and CEA in serum. Our results showed significant higher levels of ALU 247, ALU 115, CA15-3 and CEA in BC patients in comparison to healthy controls (P=0.02, 0.008, <0.001 and < 0.001 respectively). Also, cfDNA integrity index was higher in BC patients in comparison to healthy controls but statistically insignificance (p = 0.46). In recurrent BC patients; ALU 247, ALU 115, cfDNA integrity index, CA15-3 and CEA levels were higher compared to non-recurrent BC patients but with no statistic significant (p = 0.46, 0.59, 0.09, 0.85 and 0.84 respectively). This may result from the short period of follow up (1–2 years) and the relatively small sample size due to exclusion of patients with chronic diseases or inflammation as well as those who received therapy or post-surgery. By using the ROC curve, the sensitivity of ALU 247, ALU 115, CA15-3 and CEA for discriminating BC patients from BBD patients and healthy controls was 79 %, 79.2 %, 76.0 % and 88.0 % respectively. This study suggested that ALU 247, ALU 115, CA15-3 and CEA could be promising non-invasive markers of BC for diagnosis and early prediction of recurrence after validation in large-scale future studies.

The potential role of collagen type VII in breast cancer proliferation

BackgroundBreast cancer is the most common cancer in women. Cancer cells can persist in a prolonged dormant state for years without any clinical evidence of disease creating an urgent need to better understand the molecular mechanisms leading to relapse. This study aimed to identify extracellular matrix (ECM) components associated with hypoxia-induced breast cancer dormancy. The effects of selected ECM proteins on breast cancer cell proliferation were analyzed, along with their correlation with established prognostic markers in human breast cancer tissue.Materials and methodsScreening of extracellular matrix proteins was performed in hypoxia-induced dormant MCF-7 breast cancer cells. Proliferation of MCF-7 cells in vitro was subsequently determined in the presence of recombinant ColVII. Adipose tissue-derived mesenchymal stem cells (AdMSCs) subpopulation overexpressing ColVII were indirectly isolated by ColVII receptor integrin-α6 specific antibodies. AdMSCs- MCF-7 3D spheroid cultures were generated to model solid tumour conditions. In addition, the association between ColVII and various prognostic markers was evaluated in clinical samples of human breast cancer tissue.ResultsDormant MCF-7 cells showed an elevated expression of ColVII while MCF-7 cells cultured on ColVII exhibited reduced proliferation in vitro. In AdMSCs-MCF-7 3D spheroids, a reduced proliferation of MCF-7 cells was observed in Int-α6+/ ColVIIhigh compared with Int-α6-/ ColVIIlow AdMSCs spheroids. In human tissue, high ColVII expression correlated to several positive prognostic markers. Staining for Cytokeratin-5 revealed that ColVIIhigh-expressing cells were predominantly myoepithelial cells.ConclusionColVII is associated with reduced proliferation of breast cancer cells in vitro. ColVII is strongly expressed in myoepithelial cells and in breast cancer tissue the high ColVII expression correlates with several well-known positive prognostic markers, highlighting its potential as a prognostic marker in breast cancer.

Prognostic value of Maspin protein level in patients with triple negative breast cancer

The search for prognostic markers in breast cancer has bumped into a typical feature of these tumors, intra and intertumoral heterogeneity. Changes in the expression profile, localization of these proteins or shedding to the surrounding stroma can be useful in the search for new markers. In this context, classification by molecular subtypes can bring perspectives for both diagnosis and screening for appropriate treatments. However, the Triple Negative (TN) subtype, which is already the one with the worst prognosis, lacks appropriate and consistent molecular markers. In this work, we analyzed 346 human breast cancer samples in tissue microarrays (TMA) from cases diagnosed with invasive breast carcinoma to assess the expression and localization pattern of Maspin and their correlation with clinical parameters. To complement our findings, we also used TCGA data to analyze the mRNA levels of these respective genes. Our data suggests that the TN subtype demonstrates a higher level of cytoplasmic Maspin compared to the other subtypes. Maspin transcript levels follow the same trend. However, TN patients with lower Maspin expression tend to have worse overall survival and free-survival metastasis rates. Finally, we used Maspin expression data to verify possible relationships with the clinicopathological information of our cohort. Our univariate analyses indicate that Maspin is related to the expression of estrogen receptor (ER) and progesterone receptor (PR). Furthermore, Maspin expression levels also showed correlation with Scarff-Bloom-Richardson (SBR) parameter, and stromal Maspin showed a relationship with lymph node involvement. Our data is not consistently robust enough to categorize Maspin as a prognostic marker. However, it does indicate a change in the expression profile within the TN subtype.

LCP1 correlates with immune infiltration: a prognostic marker for triple-negative breast cancer

ObjectiveTriple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cytosolic protein 1), which plays a crucial role in cell processes and immune cell activity, to predict outcomes and guide treatments in TNBC.MethodsWe explored LCP1 as a potential biomarker in TNBC and investigated the mRNA and protein expression levels of LCP1. We investigated different databases, including GTEX, TCGA, GEO, cBioPortal and Kaplan-Meier Plotter. Immunohistochemistry on TNBC and benign tumor samples was performed to examine LCP1's relationship with patient clinical characteristics and macrophage markers. We also assessed survival rates, immune cell infiltration, and drug sensitivity related to LCP1 using various bioinformatics tools.ResultsThe results indicated that LCP1 expression was higher in TNBC tissues compared to adjacent normal tissues. However, high expression of LCP1 was significantly associated with favorable survival outcomes in patients with TNBC. Enrichment analysis revealed that genes co-expressed with LCP1 were significantly enriched in various immune processes. LCP1 showed a positive correlation with the infiltration of resting dendritic cells, M1 macrophages, and memory CD4 T cells, and a negative correlation with M2 macrophages. Further analysis suggested a link between high levels of LCP1 and increased survival outcomes in cancer patients receiving immunotherapy.ConclusionLCP1 may serve as a potential diagnostic and prognostic biomarker for TNBC, which was closely associated with immune cell infiltration, particularly M1 and M2 macrophages. Our findings may provide valuable insights into immunotherapeutic strategies for TNBC patients.

Multifaceted role of phytoconstituents based nano drug delivery systems in combating TNBC: A paradigm shift from chemical to natural.

Triple negative breast cancer is considered to be a malignancy of grave concern with limited routes of treatment due to the absence of specific breast cancer markers and ambiguity of other potential drug targets. Poor prognosis and inadequate survival rates have prompted further research into the understanding of the molecular pathophysiology and targeting of the disease. To overcome the recurrence and resistance mechanisms of the TNBC cells, various approaches have been devised, and are being continuously evaluated to enhance their efficacy and safety. Chemo-Adjuvant therapy is one such treatment modality being employed to improve the efficiency of standard chemotherapy. Combining chemo-adjuvant therapy with other upcoming approaches of cancer therapeutics such as phytoconstituents and nanotechnology has yielded promising results in the direction of improving the prognosis of TNBC. Numerous nanoformulations have been proven to substantially enhance the specificity and cellular uptake of drugs by cancer cells, thus reducing the possibility of unintended systemic side effects within cancer patients. While phytoconstituents offer a wide variety of beneficial active constituents useful in cancer therapeutics, most favorable outcomes have been observed within the scope of polyphenols, isoquinoline alkaloids and isothiocyanates. With an enhanced understanding of the molecular mechanisms of TNBC and the advent of newer targeting technologies and novel phytochemicals of medicinal importance, a new era of cancer theranostic treatments can be explored. This review hopes to instantiate the current body of research regarding the role of certain phytoconstituents and their potential nanoformulations in targeting specific TNBC pathways for treatment and diagnostic purposes.

Bioinformatic Investigation of Genetic Changes in Paraoxonase Genes in Breast Cancer and Breast Cancer Subtypes.

Among women, breast cancer (BC) is the most prevalent form of cancer. Many molecular targets have been discovered for BC prognosis and treatment. However, new markers still need to be identified, as cancer pathogenesis is triggered by different mechanisms. The aim of this study was to examine the changes in the paraoxonase genes (PON1, PON2, and PON 3) involved in the pathogenesis of BC. The characteristics of the mutations were evaluated with the Cbioportal database. Kaplan-Meier Plot evaluated recurrence-free survival (RFS). The UALCAN database determined the promoter methylation. Gene expression was evaluated by GEPIA2.0 database. PON1 harbored the most mutations. There was a significant decrease in PON3 expression levels in BC samples compared with healthy samples. PON1 and PON2 expression levels did not differ between BC tissue and normal adjacent tissue. Elevated expression levels of PON1 and PON2 genes were correlated with longer RFS, whereas reduced expression of the PON2 gene showed an association with longer RFS. Moreover, the promoter regions of PON1 and PON 3 were found to be hypermethylated, while the promoter region of PON 2 was found to be hypomethylated. The PON3 promoter region was significantly hypermethylated in luminal and human epidermal growth factor receptor 2 (HER2) + BC subtypes. However, the PON3 promoter region was significantly hypomethylated in the triple negative breast cancer (TNBC) subtype. These results suggest that methylation and expression status of PON3 in BC and BC subtypes (TNBC, luminal and HER2) may indicate a poor prognosis. The PON3 gene could be a negative prognostic marker in BC. However, the results should be supported by prospective studies.

Expression of Intragenic LCAL4 Long Non-Coding RNAs as a Potential Diagnostic and Prognostic Marker in Female Breast Cancer.

In breast cancer early detection is associated with reduced mortality and it is essential to identify new biomarkers for early detection and appropriate management of cancer patients with the best response to treatment. Long non-coding RNAs (LncRNAs) have attracted much attention as potential diagnostic, prognostic, or predictive biomarkers due to their high specificity, easy access to non-invasive methods, and their aberrant expression under various pathological and physiological conditions. Have attracted the aim of this study is to investigate the expression profile of intragenic non-coding LncRNAs LCAL4 as a biomarker as potential diagnostic and prognostic biomarkers in cancer. In this research, 62 tissue samples were obtained from patients undergoing therapeutic surgery in Khatam al-Anbia Hospital and the normal peripheral tissue that was removed for prevention was used as a control by Real-time PCR method. The expression pattern of LCAL4 long non-coding RNA gene is significantly different between two groups of healthy control samples and samples obtained from patients with different breast cancer subtypes, Also its expression between samples obtained from different subgroups and different stages showed significant differences. The studied LncRNAs can act as a factor to identify tumor tissue from healthy tissue, and the diagnosis of cancer grades can be different depending on the type of LncRNA. These results can be proposed in the introduction of LncRNA LCAL4 as a new marker in the diagnosis of breast cancer. In addition, by interpreting the results, it can be concluded that these LncRNAs can be considered as influential factors in the process of breast cancer.