Prognostic Biomarker For Breast Cancer Research Articles

Artificial intelligence–powered tumor-infiltrating lymphocytes analyzer to reveal distinct immune landscapes in breast cancer by molecular subtype and HER2 score.

1049 Background: Tumor-infiltrating lymphocytes (TIL) reflect an ongoing anti-tumor immune response in the tumor microenvironment (TME) and have been studied as a predictive as well as prognostic biomarker in breast cancer (BC). The immune profile differs depending on BC molecular subtypes, with triple-negative BC (TNBC) and HER2-positive BC more frequently infiltrated by higher numbers of TIL than hormone receptor (HR)-positive tumors. In this study, we analyze TIL and immune phenotype by molecular subtype in BC and explore differences based on HER2 scores using an AI-powered TIL analyzer. Methods: A total of 1,973 cases of BC with molecular subtype, HER2 immunohistochemistry (IHC) or in situ hybridization (ISH) results, and TIL analysis from H&E slides from TCGA (n=1021), Samsung Medical Center (SMC, n=663), and KyungHee Medical Center (KHMC, n=289) were included in the analysis. The density of TIL were spatially analyzed from H&E WSI, and the immune phenotype (IP) was analyzed for each 1 mm2-sized patch. Tumor microenvironment (TME) was categorized into three types: inflamed (TIL distributed intratumorally), Immune-excluded (TIL excluded, out of cancer stroma), immune-desert (scant TIL in TME), and the score for each IP was calculated as the percentage of the total patches in WSI. Results: TNBC showed the highest TIL density in both cancer epithelium (214.5 ± 299.7/mm2) and stroma (1133.3 ± 1245.9/mm2), and a high percentage of inflamed IP (35.7%), IS (28.4 ± 28.1) than other subtypes (inflamed IP: 17.5%, IS 16.2±20.2, both p<0.001). HER2-positive BCs showed higher sTIL density (904.0 ± 901.7/mm2) compared to HR- positive BC (616.7 ± 794.1/mm2) but were associated with a higher percentage of immune-excluded IP (71.2%) and IES (57.6 ± 24.6). HR-positive BC had a high percentage of immune-desert IP (30.4%). In both HR-positive and negative BCs, higher IES was observed as the HER2 score increased. HER2-positive BC significantly showed a higher proportion of cancer stroma in the cancer region from WSI (Stromal ratio, 0.682 ± 0.149 vs. 0.578 ± 0.176, p<0.001). Conclusions: Different TIL densities and IP were seen in BC for each molecular subtype, pointing to a distinct immune landscape. HER2 score was associated with immune-excluded IP despite having higher TIL density, which should be considered for immunotherapy in BC.

ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer

BackgroundCurrent studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer.MethodsARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan–Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB).ResultsARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score.ConclusionsOur findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration.

Abstract LB260: Assessing the suitability of our exosomal small ncRNAs to serve as biomarkers for breast cancer & elucidating the relationship of exosomal ncRNAs and cancer cells from t-47d and hc1143 cell lines

Abstract Background: Exosomes are known to play the role of cargo, carrying biologically important materials such as non-coding RNAs to their recipient cells. Small non-coding RNAs such as miRNA have been shown to exert strong effects on tumorigenesis. The liquid biopsy, which utilizes small RNAs from plasma exosomes, is therefore a promising tool for precision oncology. The purpose of this study is to discover exosomal miRNAs that serve as detection markers of breast cancer. Our hypothesis are 1) if exosomes play the role of cargo, then there should be an abundance of upregulated ncRNAs in exosomes that are also upregulated in the cancer cells themselves. 2) It is likely that the miRNAs in exosomes that are highly expressed have critical roles in cancer cell activity. We performed small RNA-seq and examined the ncRNAs inside cancer cells and exosomal ncRNAs secreted by cancer cells into the culture media. Methods: Two cancer cell lines T-47D and HCC1143, and primary Human Mammary Epithelial Cells (HMEC) were used. We prepared 5 samples of cellular RNA extracted from T-47D and HCC1143 and HMEC. We also extracted 8 samples of exosomal RNA from the media; which included those used for each cell culture and those never used for culture with or without FBS. Exosomes in FBS were depleted using Exosome Depletion Kits. The FASTQ files were uploaded onto QIAGEN GeneGlobe for analysis. The data was primarily normalized using geNorm. Results: Exosomal ncRNAs from both cancer cells were compared to exosomal ncRNAs from normal cells. A total of 879 ncRNAs were detected, 108 of which were significantly upregulated and 104 of which were downregulated in cancer cells. hsa-miR-196a-5p is a ncRNA that had a fold-change of 84.08. Prior studies suggest that this miRNA is associated with MIR196A2 methylation and affects the malignancy of many types of cancers. Comparing cancer exosomal ncRNAs vs. ncRNAs inside cancer cells, a total of 879 ncRNAs were found with a FDR q-value <0.05 and cut-off of 2 fold change. 251 ncRNAs were significantly upregulated in the exosomes. hsa-miR-1-3p had a fold change value of 4025.68 and an associated p-value of 0.0002. High levels of hsa-miR-1-3p are known to be associated with large tumors and is strongly correlated to a lower breast cancer survival rate. Conclusions: The preliminary results indicate that there were significant differences between exosomal ncRNAs from normal cells and exosomal ncRNAs from cancer cells. The data suggests that exosomal ncRNAs are a promising source of prognostic biomarkers for breast cancer as ncRNAs with a high fold change are repeatedly validated to have a significant impact on breast cancer progression. The data supports our hypothesis that the upregulation of ncRNAs in cancer cells & exosomes is linked to cancer activity. The results will be scrutinized further, as other avenues for data analysis will be explored. The next step in our experiment will be to check the cancer survival rates with the TCGA database and attempt to validate our hypothesis through further cell culture experiments. Citation Format: Ken D. Kobayashi, Mayumi Jijiwa, Masaki Nasu, Youping Deng. Assessing the suitability of our exosomal small ncRNAs to serve as biomarkers for breast cancer & elucidating the relationship of exosomal ncRNAs and cancer cells from t-47d and hc1143 cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB260.

High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer

Introduction: Inner centromere protein (INCENP) is a member of the chromosomal passenger complex and plays a key role in mitosis and cell proliferation. This study aimed to evaluate the clinical and prognostic significance of INCENP in invasive breast cancer (BC). Methods: INCENP expression was evaluated on a tissue microarray of a large BC cohort (n = 1,295) using immunohistochemistry. At the mRNA level, INCENP expression was assessed using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1,980) and The Cancer Genome Atlas (TCGA) BC cohorts (n = 854). The correlations between INCENP expression, clinicopathological parameters, and patient outcome were investigated. Results: INCENP expression was detected in the nucleus and cytoplasm of the tumour cells. Its expression was significantly associated with features characteristic of aggressive BC behaviour including high tumour grade, larger tumour size, and high Nottingham prognostic index scores. High INCENP nuclear expression was a predictor of shorter BC-specific survival in the whole cohort, as well as in the luminal subtype (p < 0.001). High INCENP nuclear expression was predictive of poor prognosis in BC patients who received hormone treatment or chemotherapy. Conclusion: High INCENP expression is a poor prognostic biomarker in BC with potential therapeutic benefits.

Can Caspase-3 act as a potential prognostic biomarker in breast cancer? - A retrospective pilot study in central India

Background: Caspase-3 is involved in the apoptosis induced by many agents, including antineoplastic drugs in cancers. Loss of caspase-3 expression and activity has been reported in primary human breast cancers. It is suggested that it might promote tumour development by preventing and reducing senescence. It was a retrospective observational pilot study aimed to evaluate the prognostic potential role of caspase-3 in breast cancer patients.Method: It was a retrospective observational pilot study in which fifty breast cancer patients were enrolled. Haematoxylin and eosin-stained slides of the cases were screened to obtain the best paraffin block for IHC, on which immunohistochemical expression of caspase-3 marker was done and studied. It was correlated with the known prognostic markers of breast cancer.Results: Out of 21 cases with moderate caspase-3 staining, 85.7% cases were grade III and 14.2% were grade II. From 16 cases with strong caspase-3 staining, 75% cases were grading III followed by 25% cases of grade II. There was no significant correlation between caspase-3 staining with histological grade, size of tumour, lymph node involvement, ER, PR and Her2/neu status (p=0.68, 0.24, 0.20, 0.68, 0.45 and 0.11 respectively). Correlation of survival was significantly associated with lymph node involvement (p=0.01) while it was insignificant for tumour size and histological grade (p=0.36 and 0.42 respectively).Conclusion: The survival of breast cancer patients was correlated only with lymph node metastasis. It was better with smaller number of lymph node involvement. While, Caspase-3 did not have any direct association with prognostic markers of breast carcinoma like tumour size, grade of tumour, lymph node and ER, PR and HER-2/neu status. It can be probably used as a prognostic biomarker in future if bigger study is able to establish the significance in breast cancer.

Integrated analysis of coexpression and a tumor-specific ceRNA network revealed a potential prognostic biomarker in breast cancer.

Breast cancer, a type of tumor associated with high heterogeneity, is top among the common malignancies threatening women's health worldwide. Emerging evidence suggests that competing endogenous RNA (ceRNA) plays a role in the molecular biological mechanisms related to the occurrence and development of cancer. However, the effect of the ceRNA network on breast cancer, especially the long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network, has not been fully studied. To explore potential prognostic markers of breast cancer under ceRNA network, we first extracted the breast cancer expression profiles of lncRNAs, miRNAs and mRNAs and their corresponding clinical data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) database. Next, we selected breast cancer-related candidate genes by intersection of the differential expression analysis and the weighted gene coexpression network analysis (WGCNA). Then, we studied the interactions among lncRNAs, miRNAs, and mRNAs by means of multiMiR and starBase and then constructed a ceRNA network of 9 lncRNAs, 26 miRNAs, and 110 mRNAs. We established a prognostic risk formula by means of multivariable Cox regression analysis. Based on public databases and evaluated via modeling, we identified the HOX antisense intergenic RNA (HOTAIR)-miR-130a-3p-high mobility group-box 3 (HMGB3) axis as a potential prognostic marker in breast cancer through a prognostic risk model we established using multivariable Cox analysis. For the first time, the potential interactions among HOTAIR, miR-130a-3p, and HMGB3 in the tumorigenesis were clarified, and these may provide novel prognostic value for breast cancer treatment.

Demystifying the Role of Prognostic Biomarkers in Breast Cancer through Integrated Transcriptome and Pathway Enrichment Analyses

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of death in women. Researchers have discovered an increasing number of molecular targets for BC prognosis and therapy. However, it is still urgent to identify new biomarkers. Therefore, we evaluated biomarkers that may contribute to the diagnosis and treatment of BC. We searched TCGA datasets and identified differentially expressed genes (DEGs) by comparing tumor (100 samples) and non-tumor (100 samples) tissues using the Deseq2 package. Pathway and functional enrichment analysis of the DEGs was performed using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) database. The protein-protein interaction (PPI) network was identified using the STRING database and visualized through Cytoscape software. Hub gene analysis of the PPI network was completed using cytohubba plugins. The associations between the identified genes and overall survival (OS) were analyzed using a Kaplan-Meier plot. Finally, we have identified hub genes at the transcriptome level. A total of 824 DEGs were identified, which were mostly enriched in cell proliferation, signal transduction, and cell division. The PPI network comprised 822 nodes and 12,145 edges. Elevated expression of the five hub genes AURKA, BUB1B, CCNA2, CCNB2, and PBK are related to poor OS in breast cancer patients. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation causing aneuploidy. The enriched functions and pathways included the cell cycle, oocyte meiosis, and the p53 signaling pathway. The identified five hub genes in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.

Overexpression of CHAF1A is associated with poor prognosis, tumor immunosuppressive microenvironment and treatment resistance.

Background: As distinct marker of proliferating cells, chromatin assembly factor-1 (CAF-1) was critical in DNA replication. However, there is paucity information about the clinical significance, functions and co-expressed gene network of CHAF1A, the major subunit in CAF-1, in cancer. Methods: Bioinformatic analysis of CHAF1A and its co-expression gene network were performed using various public databases. Functional validation of CHAF1A was applied in breast cancer. Results: Overexpression of CHAF1A was found in 20 types of cancer tissues. Elevated expression of CHAF1A was positively correlated with breast cancer progression and poor patients' outcome. The analysis of co-expression gene network demonstrated CHAF1A was associated with not only cell proliferation, DNA repair, apoptosis, but cancer metabolism, immune system, and drug resistance. More importantly, higher expression of CHAF1A was positively correlated with immunosuppressive microenvironment and resistance to endocrine therapy and chemotherapy. Elevated expression of CHAF1A was confirmed in breast cancer tissues. Silencing of CHAF1A can significantly inhibit cell proliferation in MDA-MB-231 cells. Conclusion: The current work suggested that overexpression of CHAF1A can be used as diagnostic and poor prognostic biomarker of breast cancer. Higher expression of CHAF1A induced fast resistance to endocrine therapy and chemotherapy, it may be a promising therapeutic target and a biomarker to predict the sensitivity of immunotherapy in breast cancer.

CD24-associated ceRNA network reveals prognostic biomarkers in breast carcinoma

Breast cancer is one of the most common cancer types which is described as the leading cause of cancer death in women. After competitive endogenous RNA (ceRNA) hypothesis was proposed, this triple regulatory network has been observed in various cancers, and increasing evidences reveal that ceRNA network plays a significant role in the migration, invasion, proliferation of cancer cells. In the current study, our target is to construct a CD24-associated ceRNA network, and to further identify key prognostic biomarkers in breast cancer. Using the transcriptom profiles from TCGA database, we performed a comprehensive analysis between CD24high tumor samples and CD24low tumor samples, and identified 132 DElncRNAs, 602 DEmRNAs and 26 DEmiRNAs. Through comprehensive analysis, RP1-228H13.5/miR-135a-5p/BEND3 and SIM2 were identified as key CD24-associated biomarkers, which exhibited highly significance with overall survival, immune microenvironment as well as clinical features. To sum up the above, the current study constructed a CD24-associated ceRNA network, and RP1-228H13.5/miR-135a-5p/BEND3 and SIM2 axis worked as a potential therapeutic target and a predictor for BRCA diagnosis and prognosis.

Abstract PD12-09: PD12-09 Serum Advanced Glycation End-Products are Associated with Breast Cancer Prognosis

Abstract Background: Tumor characteristics such as grade, stage and receptor status are associated with breast cancer (BC) prognosis. Less is known about modifiable factors and BC prognosis. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism, generated in conditions of increased oxidative stress. AGEs irreversibly accumulate in our tissues over time with pathogenic effects on genetic fidelity, protein function, cell signaling pathways, and chronic inflammatory diseases. The total body AGE pool is composed of endogenous AGEs and exogenous AGEs (consumed mainly through processed foods and those cooked at high temperatures). Serum AGE (sAGE) levels, a reflection of total body AGE, are higher in people with poor diet quality, lower levels of physical activity, and in women with BC compared to healthy controls. AGEs promote growth, migration and invasion in BC cell lines and activate prognostic inflammatory mediators such as interleukin-6 and C-reactive protein. Dietary AGEs have been associated with increased BC risk and increased mortality after BC diagnosis whereas lifestyle interventions can lower dietary and sAGE levels. The impact of sAGE levels, a better estimate of total body AGE than dietary AGE, on BC prognosis has not been previously evaluated. Methods: The Women’s Healthy Eating and Living (WHEL) study randomized 3088 BC patients stage I-III who completed their primary therapy to a high-vegetable, low-fat diet or control and followed for a median of 7.3 years. Main outcomes were invasive BC events (recurrence or new primary N=518), death due to BC (N=262) and deaths from any cause (N=315). sAGE was measured as the AGE metabolite carboxymethyllysine (ug/ml) from WHEL fasting blood specimens at study entry. sAGE was logged and corrected for plate batch effect via linear regression and analyzed in continuous scale and in quintiles. The Kaplan-Meier method and Cox regression model were performed for risk impact of sAGE on overall survival (OS), recurrence free survival (RFS), breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). We additionally adjusted in Cox models for potential confounding variables (age, race, BMI, smoking, alcohol use, physical activity, tumor characteristics). Results: 2564 participants had sAGE available. After excluding samples for excessive variabilities, 2315 samples were analyzed. Raw corrected sAGE ranged from 0.0-48.15 ug/ml (median 7.39); logged and corrected range -5.04-1.67. sAGE was positively associated with BMI (p&amp;lt;.0001, rs 0.10) and negatively associated with physical activity (p&amp;lt; .001, rs.-0.06). sAGE was not significantly associated with tumor stage, grade, receptor status, or race or menopausal status. Comparing the highest quintile (logged and corrected range=0.33~1.67) to the lowest quintile (range=-5.04~-0.30), sAGE was significantly associated with all survival outcomes (Table 1). As a continuous variable, AGE was associated with worse OS (HR 1.38, P=.031, β .32) and RFS (HR 1.29, P=.028, β .25) with a trend towards worse DMFS (HR 1.28, P=.067, β .25) and BCSS (HR 1.36, P=.06, β .31). Conclusions: Higher sAGEs are associated with worse survival outcomes in BC and may represent a novel, lifestyle-linked, modifiable prognostic biomarker in BC. Interventions aimed at lowering sAGE levels should be tested for their impact on known prognostic biomarkers as well as clinical outcomes. Individualized cancer-specific lifestyle recommendations are a crucial but currently lacking component of personalized cancer medicine. Citation Format: Lindsay L. Peterson, Yu Tao, Jingqin Luo, Graham A. Colditz, Yikyung Park, Jennifer A. Ligibel, David Turner. PD12-09 Serum Advanced Glycation End-Products are Associated with Breast Cancer Prognosis [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 PD12-09.

PHF20 is a Novel Prognostic Biomarker and Correlated with Immune Status in Breast Cancer.

Increasing evidence has demonstrated that enhanced PHF20 expression plays a crucial role in cancer development and progression. However, little is known about the prognostic value of PHF20 expression in breast cancer (BRCA). In this study, we attempted to explore the expression pattern of PHF20 and its associations with prognosis and immune status in BRCA. The gene expression data and clinical information of 1109 BRCA samples were downloaded from TCGA database. The expression level of PHF20 protein was determined using UALCAN and HPA database. Kaplan-Meier method and CIBERSORT algorithm were used to analyze the associations of PHF20 expression with overall survival (OS) and immune microenvironment, respectively. Besides, GSEA analysis was conducted to explore potential biological functions and molecular mechanisms of PHF20 in BRCA. Moreover, starBase database was applied to construct a ceRNA nework. PHF20 was highly expressed in BRCA samples both at the transcriptional and protein level, and was strongly correlated with the OS and immune status. Univariable and multivariate Cox regression analyses identified PHF20 as an independent prognostic factor. Additionally, GSEA analysis showed that high PHF20 expression was closely associated with TGF-β signaling pathway, Wnt signaling pathway, and adherens junction. Furthermore, three ceRNA networks (AC037198.1/hsa-miR-223-3p/PHF20, CBR3-AS1/hsa-miR-223-3p/PHF20, and ZNF561-AS1/hsa-miR-223-3p/PHF20) were identified by starBase analysis. Functional experiments validated that PHF20 knockdown inhibited the cell viability and progression in BRCA cells. PHF20 overexpression was significantly associated with poor prognosis and immune status in BRCA, and could act as a potential novel prognostic biomarker for BRCA.

A label-free electrochemical aptasensor based on Bi-Sb alloy materials for potential POCT of HER-2.

As a prognostic biomarker for breast cancer, human epidermal growth factor receptor 2 (HER-2) is of crucial diagnostic value. Here, a label-free electrochemical aptasensor was established for the ultrasensitive detection of HER-2 using a modified electrode of Bi-Sb alloy materials (Bi-Sb AMs). The performance of the aptasensor was enhanced greatly due to the introduction of Bi-Sb alloy materials (Bi-Sb AMs) with high conductivity. Furthermore, by integrating the aptasensor with the Sensit Smart U-disk electrochemical analyzer, the point-of-care testing (POCT) for HER-2 was realized. Under the optimal experimental parameters, the POCT analyzer showed a wide linear response from 0.01 pg mL-1 to 100 ng mL-1, with a low detection limit (LOD) of 5.96 fg mL-1 for the detection of HER-2. The presented POCT analyzer exhibited good specificity, stability, and reproducibility. Benefiting from the simple operation and rapid testing, the developed analyzer will have potential application in the prognostic diagnosis and treatment of breast cancer.

An Autophagy-Associated Prognostic Gene Signature for Breast Cancer.

Autophagy is closely related to breast cancer and has the dual role of promoting and inhibiting the progression of breast cancer. In this study, we aimed to establish an autophagy-related gene signature for the prognosis of breast cancer. A gene signature composed of the eight most survival-relevant autophagy-associated genes was identified by least absolute shrinkage and selection operator (LASSO) regression analysis. A risk score was calculated based on the gene signature, which divided breast cancer patients into low- or high-risk groups and showed good and poor prognosis, respectively. The risk score displayed good prognostic performance in both the training cohort (TCGA, 1-10-year AUC > 0.63) and the validation cohort (GEO, 1-10-year AUC > 0.66). The multivariate Cox regression and stratified analysis revealed that the risk score was an independent prognostic factor for breast cancer patients. Moreover, the high-risk score was associated with higher infiltration of neutrophils and M2-polarized macrophages, and lower infiltration of resting memory CD4+ T cells, CD8+ T cells, and NK cells. Finally, the high-risk score was associated with myc target, glycolysis, and mTORC1 signaling. The risk score developed based on the autophagy-associated gene signature was an independent prognostic biomarker for breast cancer.

Evaluation of Serum Hormones and Biochemical Tumor Markers among Breast Cancer Patients in the South-South Region, Nigeria

Breast cancer remains one of the most frequent malignancies in women and the primary cause of cancer-related death in women all over the world. Hormones and tumor biomarkers have been implicated as possible causes and prognostic biomarkers of breast cancer. The present study investigated the use of serum hormonal levels and tumor biomarkers; Carcinoembrvonic antigen (CEA), and cancer antigen (CA 15-3) for the diagnosis of Breast Cancer, and generation of different subtypes using Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This study is a cross-sectional study comprising 120 subjects; sixty breast cancer patients, and sixty apparently healthy women who served as control. One hundred and twenty blood samples were collected and analyzed for estrogen, progesterone, Carcinoembrvonic antigen, and cancer antigen. The results showed that the peak age of incidence of breast cancer was 40-49 years. Majority (56.7%) of the cases were menopausal women, while 43.3% were in their premenopausal period. Serum estrogen, cancer antigen, and Carcinoembrvonic antigen concentrations were elevated significantly (p&lt;0.05) in the breast cancer patients than the control group. Premenopausal patients have higher progesterone, estradiol, Carcinoembrvonic antigen, and cancer antigen levels than those during the postmenopausal period. HER2 negative subtype (50.0%) is the most prevalent subtype of breast cancer. 8.4% were triple negative (ER–/PR–/HER2–) cases, while 1.7% were triple positive (ER+/PR+/HER2+) cases. Breast cancer is strongly associated with hormonal changes especially estrogen and progesterone during the premenopausal and postmenopausal periods in women. Thus, the determination of the concentration of estrogen, progesterone, Carcinoembrvonic antigen, cancer antigen, and human epidermal growth factor receptor 2 statuses could help in the prognosis of breast cancer.

Identification of CISD1 as a Prognostic Biomarker for Breast Cancer.

Although CISD1 (CDGSH iron sulfur domain 1) is upregulated in many cancer types, the potential role of CISD1 in breast cancer is still unclear. The purpose of this study was to investigate its clinical significance in breast cancer. We obtained 1109 breast cancer samples and 113 normal samples from The Cancer Genome Atlas (TCGA) and GTEx databases to demonstrate the relationship between CISD1 expression and pancancer characteristics. We analysed the relationship between CISD1 and breast cancer using the t-test and the chi-square test to evaluate the expression level of CISD1 and its clinical significance in breast cancer. The prognostic value of CISD1 in breast cancer was determined by Kaplan‒Meier and Cox regression analyses. The biological pathways were screened by gene set analysis and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment analysis (ssGSEA), of which the correlation between the level of immune infiltration and the expression of CISD1 in breast cancer was then analysed. Finally, we verified the conclusion by qPCR, immunohistochemistry, and CCK8. CISD1 is highly expressed in breast cancer patients. In addition, we verified a higher expression of CISD1 expressed in the BRCA (breast cancer) cell line, whereas CISD1 has a high diagnostic value, with an AUC of 0.718. Kaplan‒Meier survival and Cox regression analyses showed that high expression of CISD1 was independently associated with adverse clinical outcomes. In turn, GO and KEGG analyses showed that most genes were related to rRNA metabolic process, rRNA processing. Moreover, PCR and immunohistochemistry showed that CISD1 in breast cancer tissues was upregulated significantly, with CCK8 results showing that the proliferation of breast cancer cells decreased after CISD1 knockout. A high level of CISD1 is associated with poor prognosis and immune infiltration in breast cancer.

Identification of PTK2 as an adverse prognostic biomarker in breast cancer by integrated bioinformatics and experimental analyses.

PTK2 is highly expressed in many cancers and is involved in cell growth, survival, migration, and invasion. However, the prognostic value of PTK2 and its potential function remain unclear in breast cancer. Therefore, we performed a comprehensive analysis of multiple public databases to explore the roles of PTK2. By integrating multiple datasets, we found that PTK2 mRNA expression in breast cancer tissue was higher than that in normal breast tissue or adjacent tissue. High PTK2 expression was associated with lymph node metastasis stage, tumor stage, breast cancer type, age, TP53 mutation, and gender and significantly predicted a poor survival outcome in breast cancer patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that PTK2 and co-expressed genes participated in the cell cycle. Immune infiltration analysis clarified that high PTK2 expression was positively correlated with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. The DNA methylation of PTK2 in breast cancer tissues was higher than that in normal tissues, and high PTK2 methylation was correlated with poor prognosis in breast cancer patients. Furthermore, 16 possible ceRNA networks related to PTK2 were constructed for breast cancer. Additionally, PTK2 knockdown could suppress the proliferation and migration ability of MCF-7 cells. These results suggest that PTK2 can be used as a prognostic biomarker for breast cancer.

Taurine upregulated 1: Prognostic biomarker in breast cancer

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Serum LAPTM4B as a Potential Diagnostic and Prognostic Biomarker for Breast Cancer.

Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is an integral membrane protein overexpressed in various cancers and may function as a prognostic tumor marker. The present study is aimed at understanding the clinical significance of serum LAPTM4B in breast cancer (BC). Serum LAPTM4B level was evaluated in 426 BC patients, 40 benign breast disease, and 80 healthy controls by ELISA. We used the receiver operator characteristic (ROC) curve to assess the diagnostic significance. 46 BC patients were recruited to monitor the dynamic change of serum LAPTM4B during adjuvant therapy (AT). In addition, sera from a subset of 330 patients undergoing AT, including anti-HER2 treatment, were collected to evaluate the association between LAPTM4B levels and AT efficacy. Descriptive and explorative statistical analyses were used to assess LAPTM4 B's potential as a diagnostic and prognostic marker in BC. Serum LAPTM4B level was significantly increased in BC patients than benign group and controls. It could well discriminate BC from healthy controls with diagnostic accuracy with an AUC of 0.912, a sensitivity of 85.9%, and a specificity of 83.8%. Compared with pre-AT, serum LAPTM4B concentration remarkably decreased after AT. In addition, patients in the invalid response group (PD + SD) showed higher LAPTM4B levels than the valid response group (PR + CR). Our results proposed that serum LAPTM4B had a high diagnostic and prognostic impact as a circulating biomarker in BC.

EIF4G1 Is a Potential Prognostic Biomarker of Breast Cancer.

Breast cancer (BRCA) is one of the most common cancers in women worldwide and a leading cause of death from malignancy. This study was designed to identify a novel biomarker for prognosticating the survival of BRCA patients. The prognostic potential of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) was assessed using RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) as training cohort and validation set, respectively. The functional enrichment analysis of differentially expressed genes (DEGs) was performed. The relationship between EIF4G1 and tumor microenvironment (TME) was analyzed. Immunotherapy responses were explored by the immunophenoscores (IPS) and tumor immune dysfunction and exclusion (TIDE) score. The Connectivity Map (CMap) was used to discover potentially effective therapeutic molecules against BRCA. Immunohistochemistry (IHC) was applied to compare the protein levels of EIF4G1 in normal and cancer tissues and to verify the prognostic value of EIF4G1. BRCA patients with increased expression of EIF4G1 had a shorter overall survival (OS) in all cohorts and results from IHC. EIF4G1-related genes were mainly involved in DNA replication, BRCA metastasis, and the MAPK signaling pathway. Infiltration levels of CD4+-activated memory T cells, macrophages M0, macrophages M1, and neutrophils were higher in the EIF4G1 high-expression group than those in the EIF4G1 low-expression group. EIF4G1 was positively correlated with T cell exhaustion. Lower IPS was revealed in high EIF4G1 expression patients. Five potential groups of drugs against BRCA were identified. EIF4G1 might regulate the TME and affect BRCA metastasis, and it is a potential prognostic biomarker and therapeutic target for BRCA.

Correlation of P53 Expression with Clinicopathological Parameters, Hormone Receptors and HER 2 Neu Status in Breast Carcinoma

Background: Progesterone receptor (PR), estrogen receptor (ER) expression, human epidermal growth factor 2 (HER 2 neu) amplification/ overexpression, and p53 nuclear protein accumulation are all significant prognostic biomarkers in breast cancer (BC). This work aims to assess the co-presence of p53 overexpression with ER, PR, and HER 2 neu expression in invasive BC specimens by IHC and compare their expression with various clinicopathological features. Objectives: To evaluate the expression of ER, PR, HER-2neu and p53 in invasive breast carcinoma specimens and to correlate the expression of p53 with ER, PR, HER-2 neu and the clinicopathological parameters. Methods: Cases of Modified Radical Mastectomy received from June 2015 to May 2017 were studied. In addition to hematoxylin and eosin sections, immunohistochemical staining was done for ER, PR, HER 2 neu and p53. The expression of ER, PR, HER 2 neu and p53 was noted and the findings were correlated with other clinicopathological parameters. Results: Among 86 cases studied most of them belonged to the age group 41-60 years (54, 62.8%). A significant positive correlation of p53 over expression with ER and PR positive tumours and Triple Negative tumours was noted. Also p53 overexpression showed a positive significant correlation with tumour grade. Conclusion: P53 overexpression in breast carcinoma indicates an aggressive clinical course and can be used as a marker of poor prognosis.