Genes In Breast Cancer Patients Research Articles

Pharmacogenetic assessment of cytostatic therapy efficacy depending on the polymorphism of T1 and M1 glutathione-S-transferase genes in breast cancer patients

Aim. To study the effect of deletion polymorphism of the GST genes (GSTT1, GSTM1) on chemotherapy (CT) efficacy in women diagnosed with breast cancer (BC) in the Primorsky Krai. Materials and methods. The study involved 132 women with breast cancer aged 23 to 79 years (mean age 48 ± 13 years) who received chemotherapy treatment. The detection of deletion (null) genotypes of GSTM1 and GSTT1 was carried out using multiplex PCR followed by an analysis of the melting curves of the reaction products. Results. Relapse-free survival (RFS) of BC patients with the “null” GSTT1 genotype was statistically significantly higher (116.7 months (9.6 years) versus 75.8 months (6.2 years)) than in patients with the “normal” GSTT genotype. Thus, in the case of the GSTT1“null” genotype, the risk of disease relapse decreased by 2.4 times (HR = 0.418, CI = 0.191–0.915, p = 0.024). Similar to GSTT1, the DFS of patients with the GSTM1 null genotype increased from 72.7 months (6 years) to 76.1 months (6.3 years). At the same time, the risk of disease relapse in carriers of the “null” GSTM1 genotype decreased by 1.7 times (HR = 0.596, CI = 0.369–0.964, p = 0.033) compared with that in carriers of the “normal” GSTM1 genotype. Conclusions. Deletion polymorphism of the GSTT1 and GSTM1 genes has a significant impact on chemotherapy efficacy in breast cancer patients. Carriers of “null” genotypes demonstrated a higher RFS and a lower risk of developing disease relapse. Further research in this direction and validation of the data obtained may contribute to individualizing the treatment of breast cancer patients, optimizing chemotherapy regimens, and reducing the number of adverse events.

Anoikis-related genes in breast cancer patients: reliable biomarker of prognosis

BackgroundBreast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear.MethodThis study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells.ResultsOne hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan–Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels.ConclusionARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.

The identification in breast cancer (BC) of novel genetic biomarkers regulating natural killer (NK) cell function, including the HLA, KIR, and CD16A (FCGR3A), may be still a challenge. We aimed to evaluate whether the combined effect of these polymorphisms has an impact on BC susceptibility and progression. 47 BC Italian patients and healthy individuals (39 females and 66 males/ females) were genotyped by Sanger sequencing (HLA-C exon 2-4 and FCGR3A- 158V/F, 48L/R/H) and PCR-SSP typing (KIR genes). HLA-C gene allele analysis showed the group C1, with HLA-C*07:02:01 allele, to be significantly associated with tumor progression (16.7% vs. 4.0%, p=0.04, OR=4.867), and instead, group C2, with HLA-C*05:01:01, was protective against disease susceptibility (0.0% vs. 7.2%, p=0.019, OR=0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (pcorr.=0.022) and an increased combined presence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to earlier stages (66.7% vs. 19.2%, p=0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p=0.012, OR=5.020) or with lymph node involvement (p=0.008, OR=6.375). Lastly, we identified different combinations of the FCGR3A-48/158 variants and KIR genes in BC patients compared to controls. Our findings suggest that in the development of BC probably exists a disorder of the NK innate immunity influenced by KIR/HLA-C gene content and FCGR3A-158 polymorphisms and that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients in therapy.

Expression pattern analysis of the MAGE family genes in breast cancer patients and hypomethylation activation in the MCF-7 cells

Melanoma antigen gene (MAGE) families are cancer-testis genes that normally show expression in the testes. However, their expressions have been linked with various types of human cancers, including BC. Therefore, the primary purposes of the present research were to assess the expression of MAGE-A, -B, and –C genes in Saudi female patients with BC and determine their regulation via the epigenetic mechanism. Ten BC samples were analyzed for the expression levels of nine MAGE-A genes, six MAGE-B genes, and three MAGE-C genes using the RT-PCR technique. All 18 evaluated genes except for MAGE-A1, -A3, -A4, and -B5 showed weak band expressions in some BC specimens. MAGE-A6 and -B2 were expressed in 40 % of the BC tissue samples, and MAGE-A9, -A10, and -B6 were expressed in 30 %. The lowest expression levels were found for MAGE-A11, -B1, -B3, -B4, -C1, and -C2 in 10 % of the BC specimens and for MAGE-A9,--B2, and --C3 in 20 % of the samples. The most frequently expressed gene was MAGE-A8 (found in 70 % of the BC samples), which suggests that it may serve as - a marker for screening of BC. In vitro treatment, the 5-aza-2′-deoxycytidine agent led to a significant rise in mRNA expressions for all tested genes related to the MAGE-A family, except for MAGE-A10. By contrast, among the genes in the MAGE-B and -C families, only MAGE-B1 and -C2 exhibited detectable mRNA expression levels after treatment.

GENETIC POLYMORPHISMS IN RAD51, RAD52 AND RAD54 GENES OF HOMOLOGOUS RECOMBINATION REPAIR PATHWAY IN BREAST CANCER: A CASE-CONTROL STUDY FROM PUNJAB

A case-control study was conducted on 600 subjects (300 cases and 300 controls) to understand the association of genetic polymorphisms of RAD51 (rs1801320, rs1801321, rs121917739, rs2619681), RAD52 (rs4987207, rs4987208) and RAD54 (rs2295466) genes in breast cancer patients and controls in population of Punjab. Genotyping of the selected SNPs of RAD51 and RAD52 gene was done by PCR-RFLP, whereas ARMS-PCR was used for RAD54 gene polymorphism. Our study identified significant associations between specific SNPs in the RAD51 and RAD52 genes and breast cancer risk. Notably, three RAD51 SNPs (rs1801320, rs1801321, and rs121917739) and one RAD52 SNP (rs4987208) showed significant genotype frequency differences between cases and controls. Genetic model analysis revealed that minor alleles of four RAD51 SNPs (rs1801320, rs1801321, rs121917739, and rs2619681) and two RAD52 SNPs (rs4987207 and rs4987208) were linked to increased breast cancer risk. Haplotype analysis further supported these findings, with 10 RAD51 haplotypes and two RAD52 haplotypes (G-G and T-G) significantly associated with higher breast cancer risk. Additionally, the GT + TT genotype of RAD52 rs4987207 was associated with lower odds of metastasis, while the TG + GG genotype of rs4987208 was linked to lymph node involvement and higher tumor grade.

Hypermethylation of the Gene Body in SRCIN1 Is Involved in Breast Cancer Cell Proliferation and Is a Potential Blood-Based Biomarker for Early Detection and a Poor Prognosis.

Breast cancer is a leading cause of cancer mortality in women worldwide. Using the Infinium MethylationEPIC BeadChip, we analyzed plasma sample methylation to identify the SRCIN1 gene in breast cancer patients. We assessed SRCIN1-related roles and pathways for their biomarker potential. To verify the methylation status, quantitative methylation-specific PCR (qMSP) was performed on genomic DNA and circulating cell-free DNA samples, and mRNA expression analysis was performed using RT‒qPCR. The results were validated in a Western population; for this analysis, the samples included plasma samples from breast cancer patients from the USA and from The Cancer Genome Atlas (TCGA) cohort. To study the SRCIN1 pathway, we conducted cell viability assays, gene manipulation and RNA sequencing. SRCIN1 hypermethylation was identified in 61.8% of breast cancer tissues from Taiwanese patients, exhibiting specificity to this malignancy. Furthermore, its presence correlated significantly with unfavorable 5-year overall survival outcomes. The levels of methylated SRCIN1 in the blood of patients from Taiwan and the USA correlated with the stage of breast cancer. The proportion of patients with high methylation levels increased from 0% in healthy individuals to 63.6% in Stage 0, 80% in Stage I and 82.6% in Stage II, with a sensitivity of 78.5%, an accuracy of 90.3% and a specificity of 100%. SRCIN1 hypermethylation was significantly correlated with increased SRCIN1 mRNA expression (p < 0.001). Knockdown of SRCIN1 decreased the viability of breast cancer cells. SRCIN1 silencing resulted in the downregulation of ESR1, BCL2 and various cyclin protein expressions. SRCIN1 hypermethylation in the blood may serve as a noninvasive biomarker, facilitating early detection and prognosis evaluation, and SRCIN1-targeted therapies could be used in combination regimens for breast cancer patients.

Stratification and prognostic evaluation of breast cancer subtypes defined by obesity-associated genes

ObjectiveBreast cancer was the most common type of cancer among women worldwide, significantly impacting their quality of life and survival rates. And obesity has been widely accepted as an important risk factor for breast cancer. However, the specific mechanisms by which obesity affects breast cancer were still unclear. Therefore, studying the impact mechanisms of obesity as a risk factor for breast cancer was of utmost importance.MethodsThis study was based on TCGA breast cancer RNA transcriptomic data and the GeneCard obesity gene set. Through single and multiple factor Cox analysis and LASSO coefficient screening, seven hub genes were identified. The independent mechanisms of these seven hub genes were evaluated from various aspects, including survival data, genetic mutation data, single-cell sequencing data, and immune cell data. Additionally, the risk prognosis model and the neural network diagnostic model were established to further investigate these seven hub genes. In order to achieve precision treatment for breast cancer (BRCA), based on the RNA transcriptomic data of the seven genes, 1226 BRCA patients were divided into two subtypes: BRCA subtype 1 and BRCA subtype 2. By studying and comparing the immune microenvironment, investigating the mechanisms of differential gene expression, and exploring the mechanisms of subnetworks, we aim to explore the clinical differences in the presentation of BRCA subtypes and achieve precision treatment for BRCA. Finally, qRT-PCR experiments were conducted to validate the conclusions of the bioinformatics analysis.ResultsThe 7 hub genes showed good diagnostic independence and can serve as excellent biomarkers for molecular diagnosis. However, they do not perform well as independent prognostic molecular markers for BRCA patients. When predicting the survival of BRCA patients, their AUC values at 1 year, 3 years, and 5 years are mostly below 0.5. Nevertheless, through the establishment of the risk prognosis model considering the combined effect of the seven hub genes, it was found that the survival prediction of BRCA patients can be significantly improved. The risk prognosis model, compared to the independent use of the seven hub genes as prognostic markers, achieved higher timeROC AUC values at 1 year, 3 years, and 5 years, with values of 0.651, 0.669, and 0.641 respectively. Additionally, the neural network diagnostic model constructed from the 7 genes performs well in diagnosing BRCA, with an AUC value of 0.94, accurately identifying BRCA patients. The two subtypes identified by the seven hub genes exhibited significant differences in survival period, with subtype 1 having a poor prognosis. The differential mechanisms between the two subtypes mainly originate from regulatory differences in the immune microenvironment. Finally, the results of this study’s bioinformatics analysis were validated through qRT-PCR experiments.Conclusion7 hub genes serve as excellent independent biomarkers for molecular diagnosis, and the neural network diagnostic model can accurately distinguish BRCA patients. In addition, based on the expression levels of these seven genes in BRCA patients, two subtypes can be reliably identified: BRCA subtype 1 and BRCA subtype 2, and these two subtypes showed significant differences in BRCA patient survival prognosis, proportion of immune cells, and expression levels of immune cells. Among them, patients with subtype 1 of BRCA had a poor prognosis.

Unveiling promising breast cancer biomarkers: an integrative approach combining bioinformatics analysis and experimental verification

BackgroundBreast cancer remains a significant health challenge worldwide, necessitating the identification of reliable biomarkers for early detection, accurate prognosis, and targeted therapy.Materials and methodsBreast cancer RNA expression data from the TCGA database were analyzed to identify differentially expressed genes (DEGs). The top 500 up-regulated DEGs were selected for further investigation using random forest analysis to identify important genes. These genes were evaluated based on their potential as diagnostic biomarkers, their overexpression in breast cancer tissues, and their low median expression in normal female tissues. Various validation methods, including online tools and quantitative Real-Time PCR (qRT-PCR), were used to confirm the potential of the identified genes as breast cancer biomarkers.ResultsThe study identified four overexpressed genes (CACNG4, PKMYT1, EPYC, and CHRNA6) among 100 genes with higher importance scores. qRT-PCR analysis confirmed the significant upregulation of these genes in breast cancer patients compared to normal samples.ConclusionsThese findings suggest that CACNG4, PKMYT1, EPYC, and CHRNA6 may serve as valuable biomarkers for breast cancer diagnosis, and PKMYT1 may also have prognostic significance. Furthermore, CACNG4, CHRNA6, and PKMYT1 show promise as potential therapeutic targets. These findings have the potential to advance diagnostic methods and therapeutic approaches for breast cancer.

Analysis for Mitochondrial Encoded Transfer RNA Leucine2 (MT-TL2) Gene in Breast Cancer Patients

Background: Breast cancer (BC) has been linked to a variety of nuclear DNA changes as well as mitochondrial DNA (mtDNA) alterations. The study aims to evaluate/analyze the association of mitochondrial transfer RNA (mt-tRNA) leucine 2 gene with BC patients. Methods: In the current study, 24 samples have been collected from various families in Peshawar. DNA was extracted from blood. Polymerase chain reaction was used to amplify the mt-tRNA MT-TL2 gene, and 20 samples were sequenced. Results: The sequence was compared with accession #NC-012920.1 of the Revised Cambridge Reference Sequence (rCRS). The results (chromatograph, nucleotide sequence, and rCRS alignment) show mutations in mt-tRNA MT-TL2 gene in our participants is not the cause of BC. Conclusion: Yet, a significant number of BC patients must be studied, and their full mtDNA must be analyzed. This will provide an indication of the potential DNA marker that might be used to prevent BC deaths at the earliest stages.

CLINICAL SIGNIFICANCE OF BRCA1 GENE SEQUENCING AND ITS PROMOTER METHYLATION TESTING IN THE SEARCH STRATEGY FOR THERAPEUTIC TARGETS IN BREAST CANCER TREATMENT.

Currently, there is a great interest in the genetic testing of BRCA1 and BRCA2 due to the fact that for patients with breast cancer (BC) with pathogenic variants of these genes, the use of the PARP inhibitors could be also provided in addition to implemented treatment protocols. The aim of this study was to characterize the molecular genetic structure of the BRCA1 gene in BC patients without progenitor germline mutations taking into account the methylation state of the promoter region. The study involved 210 patients with newly diagnosed BC. The most common germline pathogenic variants of the BRCA1 (185delAG, 5382insC, 4153delA, T300G) and BRCA2 (6174delT) genes were identified in the peripheral blood. A subgroup of 14 patients without progenitor pathological variants of the BRCA1 and BRCA2 genes and with a family history of cancer was randomly selected. For them, BRCA1 gene sequencing by Sanger and hypermethylation of the BRCA1 gene promoter region were analyzed. The following frequencies of BRCA1 mutations were determined in the general group: 5382insC - 8.6%, 4153delA - 0.5%, T300G - 0.5%. The analysis of the BRCA1 gene by Sanger sequencing revealed 11 BRCA1 gene variants in 10 out of 14 BC patients. All of them, according to the currently available data, were defined as "benign" and not clinically relevant. The frequency of the detection of hypermethylation of the BRCA1 gene promoter region in the randomly selected group of patients was 14.3%. In BC patients, not only common mutations but also the methylation status of the BRCA1 gene promoter region in the peripheral blood should be determined. The whole-genome sequencing of the BRCA1 gene may be the last step in determining the genetic characteristics of BC patients carried out to optimize the treatment and improve survival thanks to the higher prevalence of the progenitor mutations and hypermethylation of the BRCA1 gene promoter.

Clinical importance and PI3K/Akt pathway-dependent anti-proliferative role of PALMD and DPT in breast cancer

This study aimed to identify novel differentially expressed genes in breast cancer and to explore the clinical value and the anti-tumor or oncogenic effects of the identified genes using bioinformatics analysis and in vitro experiments. The differentially expressed genes in breast cancer patients were identified using Gene Expression Omnibus (GEO) database with the cut-off criteria p < 0.05 and |logFC| > 1. The expression levels of palmdelphin (PALMD) and dermatopontin (DPT) in normal tissues and breast cancer tissues were evaluated based on GEPIA and UALCAN databases. PALMD and DPT expression levels in clinical subgroups of patients with breast cancer were analyzed to assess the association of PALMD and DPT expression with clinical characteristics. The prognostic and diagnostic values of PALMD and DPT in breast cancer were evaluated from Kaplan-Meier (K-M) survival curves and receiver operating characteristic (ROC) curves. Pearson’s correlation coefficient was performed using LinkedOmics. KEGG pathway enrichment analysis was performed using DAVID. The protein levels were evaluated using western blot analysis. Cell proliferation was assessed using MTT and EdU assays. Two important genes, PALMD and DPT, were identified in breast cancer. The expression levels of PALMD and DPT were significantly lower in breast cancer tissues. The expression levels of PALMD were closely related to age, histological type, and T stage of breast cancer patients. The expression levels of DPT were closely related to age, histological type, T stage, N stage, estrogen receptor status, and progesterone receptor status of breast cancer patients. The K-M survival curves showed that PALMD or DPT was not an independent prognostic factor for breast cancer. The ROC curves showed that both PALMD and DPT had good diagnostic potential for breast cancer. KEGG pathway enrichment results showed that PI3K/Akt pathway was an important overlapping signaling for PALMD and DPT. Further studies proved that overexpression of PALMD and DPT inhibited proliferation in MCF-7 and MDA-MB-231 cells by suppressing the PI3K/Akt pathway. PALMD and DPT knockdown promoted proliferation in MCF-7 and MDA-MB-231 cells by activating the PI3K/Akt pathway. These results collectively suggested that PALMD and DPT might serve as potential diagnostic biomarkers and therapeutic targets for breast cancer.

Retracted: Application of Fluorescence In Situ Hybridization Assisted by Fluorescence Microscope in Detection of Her2 Gene in Breast Cancer Patients.

[This retracts the article DOI: 10.1155/2022/3087681.].

Prevalence of Pathogenic Germline Mutations in 13 Hereditary Cancer-Related Genes in Breast Cancer Patients in Narathiwat Province, Thailand.

BRCA1 and BRCA2 genes are known to increase breast cancer's lifetime risk. Early identification of women with this inherited risk can potentially reduce the risk of breast and/or ovarian cancer and, together with early screening, decrease the mortality rate. This study explored the frequency and distribution of genetic variants in consecutive cases of breast cancer in Narathiwat province, one of the three provinces in the southernmost Thai border. A series of 64 consecutive breast cancer patients who underwent treatment in two general hospitals in the province during the period from the year 2021 to 2022. Genotyping studies were performed using a whole exome sequencing platform. Moderate to high penetrance variants recommended by the National Comprehensive Cancer Network (NCCN) guidelines 2022 (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53) were annotated and filtered for pathogenic, likely pathogenic, or high-impact variants. Pathogenic germline variants were found in 8/64 cases (12.5%), namely BRCA1 in 3 (4.7%), BRCA2 in 4 (6.3%), ATM in 1 (1.6%), and PALB2 in 1 (1.6%). One patient had two concomitant germline mutations in BRCA2 and ATM. This is the first study on the frequency of germline mutations in BRCA1/2 and other breast cancer-predisposing genes in the southernmost provinces of Thailand. At least one pathogenic germline mutation was identified in 12.5% of the study patients, which suggests that genetic testing in this population has a high potential to provide benefits.

Methylation status of potential genes in breast cancer patients and correlate them with gene expression

Breast cancer is one of the world’s most prevalent cancer among women. Globally approximately 2.3 million women are diagnosed with breast cancer in 2020. It arises due to epigenetic modification which outlooks aberrant methylation as its major cause. The methylation of DNA involves a covalent chemical modification which is one of the major drawback, promoting development of breast cancer. In addition, evidence and investigation suggest that these methylations at promoter region of CpG islands leads to silencing of gene associated with tumor suppressor which is involved in crucial gene expression leading to establishment of breast cancer. Among variety of hyper methylated gene involved in different function linked with breast cancer, the hyper methylation of BRCA1 gene is identified as the targeted gene in precipitating disorder. A lot of susceptible genes are identified and based on their penetrance ability are being classified In order to analyze DNA methylation status Bisulfite sequencing is employed which is based on the mechanism of converting every un-methylated cytosine into uracil. With the advancement in gene sequencing the concept of whole genome bisulfite sequencing is also on the way to determine the DNA methylation occurring at single base. Another robust and sensitive approach to determine the methylated status is RT-PCR, a diagnostic tool applied in order to detect the expression of single gene

Polymorphism of folate metabolism genes in breast cancer patients

Breast cancer is a widespread oncological disorder, which is considered one of the leading causes of mortality among women. DNA repair processes a well as its methylation involving genes of folate cycle play a crucial role in cancerogenesis. The aim of the study is to generalize the current data about association between polymorphic variants of folate cycle genes MTHFR С677Т (rs1801133), MTR A2756G (rs1805087), MTRR А66G (rs1801394) with risk of breast cancer development. The search of scientific papers has been conducted using PubMed and elibrary.ru sources. Original and randomized surveys published from 2008 till 2022 have been included in this review.&#x0D; The study has accumulated sufficient data on MTHFR С677Т polymorphic variant in breast cancer patients, having significant influence on disease development. However, the data about MTR A2756G and MTRR A66G variants is quite limited. According to the findigs of many scientific papers, there is no link between polymorphic variants of these genes and breast cancerogenesis manifestation. Such factors like ethniсity and sufficient consumption of folates with nutrition can have significant impact on results and conclusions of studies about role of folate cycle genes in breast cancer patients.&#x0D; Further investigation of MTHFR С677Т (rs1801133), MTR A2756G (rs1805087) and MTRR А66G (rs1801394) genetic polymorphic variants with consideration of gene-environment and gene-gene interactions could explain the presence of individual differences of breast cancer risk.

Mutation Profiling of PI3K/AKT1/MTOR Pathway Genes in Breast Cancer Patients of Pakistan Muhammad

Mutation Profiling of PI3K/AKT1/MTOR Pathway Genes in Breast Cancer Patients of Pakistan Muhammad

Identification and analysis of dysregulated fatty acid metabolism genes in breast cancer subtypes.

Breast cancer is one of the most aggressive and lethal types of transformation among women. An anomaly of normal fatty acid metabolism is acknowledged as a critical trigger for malignant transformations including breast cancer, but the prospect of targeting fatty acid metabolism for the treatment of malignancy has remained unrecognized so far. It has been observed that specific fatty acid metabolism genes are involved in the commencement and development of breast cancer. These specific genes have also been observed to be related to different isotypes/molecular subtypes of breast cancer. The main purpose of this study was to scrutinize the prognostic significance, functional role, and expression pattern of fatty acid metabolism genes. In-Silico tools like TCGA BrCA, Gepia2, Ualcan Analysis, UCSC Xena, Kaplan-Meier plotter, Bc-gene EXminer, String, gene ontology, and KEGG databases, were used to assess the expression pattern of the fatty acid metabolism genes in breast cancer patients and also among the different molecular sub-types of breast cancer. Differential gene expression analysis revealed dysregulation of FABP4, FABP5, PLIN1,PLIN2, PLIN4, PLIN5, LPIN1, MGLL, PNPLA2, PNPLA7, ACSL1, and ACOX2 showing a fold change > ± 1.5. Also, most of these genes show downregulation in Ualcan analysis of different isotypes/molecular subtypes of breast cancer. The study reveals that the screened genes i.e., FABP4, FABP5, PLIN1,PLIN2, PLIN4, PLIN5, LPIN1, MGLL, PNPLA2, PNPLA7, ACSL1, and ACOX2 can be used as biomarkers that reveal poor prognosis and may serve as therapeutic targets for the treatment of breast cancer.

Overexpression of TIGAR and HO-1 in peripheral blood mononuclear cells (PBMCs) of breast cancer patients treated with radiotherapy

Introduction Radiation therapy (RT) is one of the primary treatment choices for breast cancer. In reaction to RT, many metabolic processes in the body are triggered, some of which have a role in counteracting free radicals in cancer cells. As a result, it is important to comprehend the effects of RT on multiple genes, biomarkers and enzymes in the body. Methods and materials Peripheral blood mononuclear cells (PBMCs) were obtained from 83 breast cancer patients in pre-and post- RT (50 Gray (Gy) in 25 fractions). The TIGAR and HO-1 gene expressions were investigated by quantitative real-time PCR (qRT-PCR). Serum bilirubin, total antioxidant capacity (TAC), total protein (TP), alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were assayed in serum patients before and after RT. Results We found that bilirubin (p = .001), ALT (p = .04), and AST (p = .03) were significantly increased, while TAC (p < .001) and TP (p = .001) were decreased after RT. However, albumin and ALP did not change after RT (p > .05 for both). Interestingly, RT led to overexpression of TIGAR (p = .004) and HO-1 (p = .003) genes in breast cancer patients. Conclusions The findings of this study showed that RT could overexpress TIGAR and HO-1 in PBMCs of breast cancer patients. More research is required to figure out the mechanisms behind the impacts of RT on increased catabolism and production of bilirubin or increased activity of TIGAR-related pathways and overexpression of TIGAR and HO-1.

The rs1940475 polymorphism in the MMP8 gene as a protective factor of severe breast cancer

Aim: to investigate an association between polymorphism in the MMP2, MMP8, MMP9 genes and severe breast cancer (BC).Materials and Methods. Retrospective comparative study was conducted by assessing a cohort of 345 BC patients: 254 patients at stage I–II and 91 at stage III–IV. Genotyping of the three single nucleotide polymorphisms in the MMP2 (C&gt;T rs243865), MMP8 C&gt;T rs1940475), and ММР9 (C&gt;T rs3918242) genes was performed. A comparative analysis of the genetic characteristics of patients with stage I–II and stage III–IV of the disease was performed.Results. The allele variant T rs1940475 (C&gt;T) of the MMP8 gene in BC patients at stage I–II (0.512) was found by 1.2-fold more often compared with patients at stage III–IV of the disease (0.428; pperm = 0.05). According to allelic (odds ratio (OR) = 0.71; 95 % confidence interval (CI) = 0.51–1.00; pperm = 0.05) and additive (OR = 0.69; 95 % CI = 0.48–0.99; pperm = 0.05) genetic models, the allele T rs1940475 (C&gt;T) of the MMP8 gene has protective effect for developing stage III–IV BC. The polymorphic locus rs1940475 (C&gt;T) determines the amino acid substitution in the MMP8 protein (p.K87E) and DNA binding to the transcription factors NF-AT1, MYC and CIZ, is associated with the expression of the genes MMP27 and RP11-817J15.3 acting as an enhancer regulatory site in primary breast epithelial cells. Single nucleotide polymorphism in the MMP2 (C&gt;T rs243865), ММР9 (C&gt;T rs3918242) genes is not associated with severe BC (stages III–IV).Conclusion. The single nucleotide polymorphism rs1940475 in the MMP8 gene is a protective factor protecting against severe BC course.

Management Strategies of Breast Cancer Patients with BRCA1 and BRCA2 Pathogenic Germline Variants.

Most of breast cancer cases are sporadic; however, 15–20% are associated with family history, and some are inherited. Among those, deleterious mutations in BRCA1 and BRCA2 tumor suppressor genes are the most commonly encountered pathogenic germline variants (PGVs). Given the availability and affordability of multi-gene panel sequencing technologies, testing for PGVs is commonly practiced. With our enhanced understanding of cancer genetics and specific molecular alterations, the better acceptance of risk-directed screening and prevention, and the recent introduction of novel targeted therapies, management of BRCA-positive breast cancers is taking a new direction, focusing more on risk-reducing interventions, including mastectomy and salpingo-oophorectomy, and incorporating special treatment regimens, including platinum-based chemotherapy, and the recently-introduced PARP (poly (ADP)-ribose polymerase) inhibitors. Given the recent advances in reproductive technology and molecular medicine, younger women with PGVs may have the option of embryo selection through preimplantation genetic testing and diagnosis, thus preventing the potential transmission of the implicated genes to the next generations. In this review, we cover the clinical implications of identifying a pathogenic germline mutation in BRCA1 and BRCA2 genes in breast cancer patients, and their relatives, across the continuum of care – from cancer prevention and early detection, through active treatment and up to survivorship issues.