scholarly journals Computational analysis and verification of molecular genetic targets for glioblastoma

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Liang Xue ◽  
Haibing Liu ◽  
Yehuang Chen ◽  
Liangfeng Wei ◽  
Jingfang Hong
Keyword(s):  
Target Genes ◽  
Statistical Significance ◽  
Molecular Genetic ◽  
Specific Treatment ◽  
Disease Free Survival ◽  
Differentially Expressed ◽  
P Value ◽  
Normal Brain ◽  
Hub Genes ◽  
Brain Tissues

Abstract Background: Glioblastoma (GBM) is the most common malignant brain tumor with a poor prognosis. The initial treatment for high-grade gliomas is surgical excision. However, even with concomitant use of radiation or chemotherapy, patients are still prone to recurrence. The specific pathogenesis of GBM is still controversial. Methods: Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between GBM and normal brain tissues were screened. P-value was obtained by Bayes test based on the limma package. Statistical significance was set as P-value <0.05 and |Fold change (FC)| > 0.2 (GSE90886); P-value <0.05 and |FC| > 1 (GSE116520, GSE103228). Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network were performed. Hub genes were selected from miRNA target genes and DEGs. GBM and normal brain tissues were extracted to verify the expression. Results: A total of 100 DEGs were overlapped in both datasets. Analysis of pathways and process enrichment tests indicated that ion transport, positive regulation of macromolecule metabolic process, cell cycle, axon guidance were enriched in the GBM. Sixteen hub genes were identified. Hub genes ADARB1 and neuropilin 1 (NRP1) were significantly associated with overall survival (OS) and disease-free survival (DFS) (P<0.05). Eukaryotic translation termination factor 1 (ETF1) was associated with DFS (P<0.05). Conclusions: DEGs and DEMs were found between GBM tumor tissues and normal brain tissues. These biomarkers may be used as targets for early diagnosis and specific treatment.

scholarly journals Human Endogenous Retroviruses in Glioblastoma Multiforme

2021 ◽  
Vol 9 (4) ◽  
pp. 764
Author(s):  
Zihao Yuan ◽  
Yuntao Yang ◽  
Ningyan Zhang ◽  
Claudio Soto ◽  
Xiaoqian Jiang ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Repetitive Elements ◽  
Endogenous Retroviruses ◽  
Differentially Expressed ◽  
P Value ◽  
Normal Brain ◽  
Sequencing Data ◽  
Significant Differential Expression ◽  
Human Endogenous Retroviruses ◽  
Brain Tissues

Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor. It is primarily diagnosed in the elderly and has a 5-year survival rate of less than 6% even with the most aggressive therapies. The lack of biomarkers has made the development of immunotherapy for GBM challenging. Human endogenous retroviruses (HERVs) are a group of viruses with long terminal repeat (LTR) elements, which are believed to be relics from ancient viral infections. Recent studies have found that those repetitive elements play important roles in regulating various biological processes. The differentially expressed LTR elements from HERVs are potential biomarkers for immunotherapy to treat GBM. However, the understanding of the LTR element expression in GBM is greatly lacking. Methods: We obtained 1077.4 GB of sequencing data from public databases. These data were generated from 111 GBM tissue studies, 30 GBM cell lines studies, and 45 normal brain tissues studies. We analyzed repetitive elements that were differentially expressed in GBM and normal brain samples. Results: We found that 48 LTR elements were differentially expressed (p-value < 0.05) between GBM and normal brain tissues, of which 46 were HERV elements. Among these 46 elements, 34 significantly changed HERVs belong to the ERV1 superfamily. Furthermore, 43 out of the 46 differentially expressed HERV elements were upregulated. Conclusion: Our results indicate significant differential expression of many HERV LTR elements in GBM and normal brain tissues. Expression levels of these elements could be developed as biomarkers for GBM treatments.

scholarly journals MicroRNA expression analysis for identification of biomarkers in inflammatory bowel disease subtypes

2020 ◽  
Author(s):  
Manisha Mandal ◽  
Shyamapada Mandal
Keyword(s):  
Ribosome Biogenesis ◽  
Target Genes ◽  
Proteasomal Degradation ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Hub Gene ◽  
Protein Protein Interaction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Protein Protein Interaction Networks

Abstract The potential biomarkers in inflammatory bowel diseases (IBDs) were analyzed from GSE53867 dataset. Differentially expressed microRNAs (DEMs)-genes and protein-protein interaction networks were constructed, and hub genes selected using Cytoscape. Differentially expressed genes were analyzed for GO and Reactome-pathway. Seven DEMs were upregulated in Crohn's disease (CD), 4 downregulated in ulcerative colitis (UC), 8 upregulated and 2 downregulated in IBD. A 620, 2377, and 1821 target-genes were in CD, UC, and IBD, respectively. SOCS3, upregulated by miR-650, was hub gene in CD, induced by cytokines, through NFKB-signalling pathway to mediate ubiquitin-proteasomal degradation. CIRH1A, downregulated by miR-16, was hub gene of UC, acted by impairing ribosome-biogenesis. SKP2 and ASB1, up- and downregulated, by miR-142 and miR-665, respectively, were hub genes of IBD, induced cytokines through activation of TLR- and TNF-signalling pathways to mediate ubiquitin-proteasomal degradation. SOCS3, CIRH1A, SKP2 and ASB1 genes might serve as valuable biomarkers to differentiate CD, UC and IBD.

scholarly journals Identification of Differentially Expressed MicroRNAs and Their Potential Target Genes in Adipose Tissue from Pigs with Highly Divergent Backfat Thickness

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 624
Author(s):  
Kai Xing ◽  
Xitong Zhao ◽  
Yibing Liu ◽  
Fengxia Zhang ◽  
Zhen Tan ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Patterns ◽  
Fat Deposition ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Backfat Thickness ◽  
P Value ◽  
Sibling Pairs ◽  
Differentially Expressed Mirnas

Fatty traits are very important in pig production. However, the role of microRNAs (miRNAs) in fat deposition is not clearly understood. In this study, we compared adipose miRNAs from three full-sibling pairs of female Landrace pigs, with high and low backfat thickness, to investigate the associated regulatory network. We obtained an average of 17.29 million raw reads from six libraries, 62.27% of which mapped to the pig reference genome. A total of 318 pig miRNAs were detected among the samples. Among them, 18 miRNAs were differentially expressed (p-value < 0.05, |log2fold change| ≥ 1) between the high and low backfat groups; 6 were up-regulated and 12 were down-regulated. Functional enrichment of the predicted target genes of the differentially expressed miRNAs, indicated that these miRNAs were involved mainly in lipid and carbohydrate metabolism, and glycan biosynthesis and metabolism. Comprehensive analysis of the mRNA and miRNA transcriptomes revealed possible regulatory relationships for fat deposition. Negatively correlated mRNA–miRNA pairs included miR-137–PPARGC1A, miR-141–FASN, and miR-122-5p–PKM, indicating these interactions may be key regulators of fat deposition. Our findings provide important insights into miRNA expression patterns in the backfat tissue of pig and new insights into the regulatory mechanisms of fat deposition in pig.

scholarly journals Construction of a Potential Breast Cancer-Related miRNA-mRNA Regulatory Network

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Xinhong Liu ◽  
Feng Chen ◽  
Fang Tan ◽  
Fang Li ◽  
Ruokun Yi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Target Genes ◽  
Differential Expression Analysis ◽  
Mirna Gene ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Epithelial Tissue ◽  
Hub Genes ◽  
Geo Database

Background. Breast cancer is a malignant tumor that occurs in the epithelial tissue of the breast gland and has become the most common malignancy in women. The regulation of the expression of related genes by microRNA (miRNA) plays an important role in breast cancer. We constructed a comprehensive breast cancer-miRNA-gene interaction map. Methods. Three miRNA microarray datasets (GSE26659, GSE45666, and GSE58210) were obtained from the GEO database. Then, the R software “LIMMA” package was used to identify differential expression analysis. Potential transcription factors and target genes of screened differentially expressed miRNAs (DE-miRNAs) were predicted. The BRCA GE-mRNA datasets (GSE109169 and GSE139038) were downloaded from the GEO database for identifying differentially expressed genes (DE-genes). Next, GO annotation and KEGG pathway enrichment analysis were conducted. A PPI network was then established, and hub genes were identified via Cytoscape software. The expression and prognostic roles of hub genes were further evaluated. Results. We found 6 upregulated differentially expressed- (DE-) miRNAs and 18 downregulated DE-miRNAs by analyzing 3 Gene Expression Omnibus databases, and we predicted the upstream transcription factors and downstream target genes for these DE-miRNAs. Then, we used the GEO database to perform differential analysis on breast cancer mRNA and obtained differentially expressed mRNA. We found 10 hub genes of upregulated DE-miRNAs and 10 hub genes of downregulated DE-miRNAs through interaction analysis. Conclusions. In this study, we have performed an integrated bioinformatics analysis to construct a more comprehensive BRCA-miRNA-gene network and provide new targets and research directions for the treatment and prognosis of BRCA.

Analysis of the miRNA transcriptome during testicular development and spermatogenesis of the Mongolian horse

2020 ◽  
Vol 32 (6) ◽  
pp. 582
Author(s):  
Bei Li ◽  
Xiaolong He ◽  
Yiping Zhao ◽  
Dongyi Bai ◽  
Dandan Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Mammalian Species ◽  
Mature Mirnas ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
P Value ◽  
Testicular Development ◽  
Interaction Sites ◽  
Mongolian Horse

Numerous studies have shown that microRNAs (miRNAs) are essential for testicular development and spermatogenesis. In order to further characterise these physiological processes, three immature and three mature testes of the Mongolian horse were collected and six libraries were established. Using small RNA sequencing technology, 531 mature miRNAs were identified, including 46 novel miRNAs without previously ascribed functions. Among the 531 miRNAs, 421 were expressed in both immature and mature libraries, 65 miRNAs were found solely in immature testis libraries and 45 miRNAs were found solely in mature testis libraries. Furthermore, among the miRNAs that were identified in both immature and mature libraries, 107 were significantly differentially expressed (corrected P value (padj)&lt;0.05). Among the miRNAs that were only expressed in immature testes, two miRNAs were differentially expressed, whereas among the miRNAs that were only expressed in mature testes, nine miRNAs were differentially expressed. Comprehensive analysis of miRNA and mRNA expression profiles predicted 107 miRNA–mRNA interaction sites. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis of the predicted target genes suggested roles of the differentially expressed miRNAs in testicular development and spermatogenesis. These findings identify miRNAs as key factors in the development of the testes and spermatogenesis in the Mongolian horse, which may also help us to understand the mechanisms of fertility in related mammalian species.

Identification of ERG Specific Target Genes by Genome-Wide Screening in T-Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3788-3788
Author(s):  
Liliana H Mochmann ◽  
Konrad Neumann ◽  
Juliane Bock ◽  
Jutta Ortiz Tanchez ◽  
Arend Bohne ◽  
...  
Keyword(s):  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Specific Treatment ◽  
P Value ◽  
Dna Templates ◽  
Genome Wide ◽  
A Genome ◽  
On Chip ◽  
T Cell Leukemogenesis ◽  
The Impact

Abstract The Ets related gene, ERG, encodes a transcription factor with a vital role in hematopoiesis. Recent findings have shown that ERG knockout mice require a minimum of one functional allele to ensure embryonic blood development and adult stem cell maintenance. Moreover, it was earlier reported that enforced expression of ERG induced oncogenic transformation in 3T3 cells. Overexpression of ERG, observed in a subset of acute T-lymphoblastic and acute myeloid leukemia patients, was associated with an inferior outcome. However, the impact of ERG contributing to this unfavourable phenotype has yet to be determined, as downstream targets of ERG in leukemia remain unknown. Herein, we conducted a genome-wide analysis of ERG target genes in T-lymphoblastic leukemia. Chromatin immunoprecipitation-on-chip array (ChIP-on-chip) analyses were performed using two ERG specific antibodies for the enrichment of ERG-bound DNA templates in T-lymphoblastic leukemia cells (Jurkat) with input DNA or IgG precipitated DNA as controls. Enriched DNA templates and control DNA were differentially labelled and co-hybridized to high resolution promoter chip arrays with 50–75mer probes (770,000) representing 29,000 annotated human transcripts (NimbleGen). Based on two independent ChIP-on-chip assays, bioinformatic analysis (ACME) yielded statistically significant enriched peaks (using a sliding window of 1000 bp, and a P-value < 0.0001) identifying promoter regions of 365 potential ERG target genes. From these genes, clustering by functional annotation was performed using the DAVID database and subsequently genes related to leukemia were further selected for quantitative PCR validation. The design of promoter primers included the highly conserved ETS GGAA DNA binding site. Genes with greater than two-fold enrichment (ERG ChIP versus control) included WNT2 (17-fold), OLIG2 (14-fold), WNT11 (7-fold), CCND1 (5-fold), WNT9A (4-fold), CD7 (3-fold), EPO (3-fold), ERBB4 (3-fold), RPBJL (3-fold), TRADD (3-fold), PIWIL1 (2-fold), TNFRSF25 (2-fold), TWIST1 (2-fold), and HDAC4 (2-fold). Interestingly, enriched target genes involved in developmental processes (WNT2, WNT9A, WNT11, TWIST1, PIWIL1, ERBB4, and OLIG2) have shown oncogenic potential when mutated or overexpressed. Thus, we hypothesize that overexpression of ERG may contribute to T-cell leukemogenesis by the deregulation of these oncogenic targets. Further disclosure of ERG directed downstream pathways may contribute to the design of specific treatment strategies (such as WNT inhibitors) with particular effectiveness in ERG deregulated leukemia.

scholarly journals Bioinformatics analysis of potential core genes for glioblastoma

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Yu Zhang ◽  
Xin Yang ◽  
Xiao-Lin Zhu ◽  
Jia-Qi Hao ◽  
Hao Bai ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Protein Interactions ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Normal Brain ◽  
Hub Genes ◽  
Potential Core ◽  
Core Genes

Abstract Background: Glioblastoma (GBM) has a high degree of malignancy, aggressiveness and recurrence rate. However, there are limited options available for the treatment of GBM, and they often result in poor prognosis and unsatisfactory outcomes. Materials and methods: In order to identify potential core genes in GBM that may provide new therapeutic insights, we analyzed three gene chips (GSE2223, GSE4290 and GSE50161) screened from the GEO database. Differentially expressed genes (DEG) from the tissues of GBM and normal brain were screened using GEO2R. To determine the functional annotation and pathway of DEG, Gene Ontology (GO) and KEGG pathway enrichment analysis were conducted using DAVID database. Protein interactions of DEG were visualized using PPI network on Cytoscape software. Next, 10 Hub nodes were screened from the differentially expressed network using MCC algorithm on CytoHubba software and subsequently identified as Hub genes. Finally, the relationship between Hub genes and the prognosis of GBM patients was described using GEPIA2 survival analysis web tool. Results: A total of 37 up-regulated and 187 down-regulated genes were identified through microarray analysis. Amongst the 10 Hub genes selected, SV2B appeared to be the only gene associated with poor prognosis in glioblastoma based on the survival analysis. Conclusion: Our study suggests that high expression of SV2B is associated with poor prognosis in GBM patients. Whether SV2B can be used as a new therapeutic target for GBM requires further validation.

scholarly journals SAT-455 Mouse Thyroid Responds to Iodine Overload by Transcriptionally Enhancing the Keap1/Nrf2 Antioxidant Response and by Upregulating Nrf2-Dependent and Independent Inflammatory and Fibrosis Pathways

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dionysios V Chartoumpekis ◽  
Panos Ziros ◽  
Ioannis Habeos ◽  
Venetsana Kyriazopoulou ◽  
Adam Smith ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Sodium Iodide ◽  
Target Genes ◽  
Rna Extraction ◽  
Xenobiotic Metabolism ◽  
Antioxidant Response ◽  
Differentially Expressed ◽  
P Value ◽  
Rna Seq ◽  
Thyroid Cells

Abstract Nrf2 (Nfe2l2) is a transcription factor that regulates a series of cytoprotective and antioxidant enzymes. Its cytoplasmic inhibitor Keap1 senses the presence of oxidative or electrophilic stress though the interaction of sulfhydryl groups of its cysteines with reactive species and ceases to bind Nrf2. Thus, Nrf2 can transfer to the nucleus and induce its target genes. Follicular thyroid cells have physiologically high levels of reactive oxygen species as oxidation of iodine is essential for iodination of thyroglobulin and thyroid hormones synthesis. We have shown previously that Nrf2 pathway is active in thyroid and regulates the transcription of thyroglobulin. We thus hypothesized that the response of thyroid to iodine excess should comprise Nrf2-dependent and -independent pathways. To this end, 3 months-old male C57Bl6J WT or Nrf2 knockout (KO) mice were exposed to 0.05% sodium iodide in their water for 7 days. Thyroids were excised and used for RNA extraction; RNA-seq was performed by Exiqon, with a fold-change cutoff set at 2. Selected representative genes of the enriched pathways were quantified by real-time qPCR to validate RNA-seq results. Pathway analysis of the differentially expressed genes was performed using the Ingenuity Pathway Analysis (IPA) software. Pathways that were enriched with a p-value&lt;0.05 were considered significant. 828 genes were differentially expressed in response to iodine exposure; 66% were upregulated, as were most of the highly enriched pathways (related to inflammatory-immune response, antioxidant response, xenobiotic metabolism, platelet activation and calcium signaling). About 300 genes were differentially expressed between WT and KO mice; highly enriched pathways were related to glutathione and xenobiotic metabolism, Ahr signaling and Nrf2 signaling and were all downregulated in KO mice. Analysis of the potential upstream regulators of these highly enriched pathways revealed that Nrf2 and NfkB are major regulators of the antioxidant and inflammatory response induction upon iodine exposure and that Tgfβ-Smad cascade regulates the induction of fibrosis signaling. Last, we performed an analysis limited to already known thyroid pathways. A few genes were enriched following this method; upregulation of Duoxa1 (hydrogen peroxide generator) and downregulation of Nis (sodium iodide symporter) upon iodine exposure, which are expected responses, and the downregulation of thyroglobulin and upregulation of Duoxa1 in KO mice that confirm our previous findings. In conclusion, Nrf2-driven cytoprotective response is upregulated after iodine overload along with induction of inflammatory pathways. Nrf2 regulates transcriptomic responses in the thyroid, including a small but significant part of the response to iodine challenge. Hence, Nrf2 can be considered a novel player in the frontiers of thyroid antioxidant response and thyroid economy.

scholarly journals Identification of miRNA-mRNA network and immune-related gene signatures in IgA nephropathy by integrated bioinformatics analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shi-Yao Wei ◽  
Shuang Guo ◽  
Bei Feng ◽  
Shang-Wei Ning ◽  
Xuan-Yi Du
Keyword(s):  
T Cells ◽  
Iga Nephropathy ◽  
Immune Cells ◽  
Regulatory Network ◽  
Target Genes ◽  
Immune Cell ◽  
Expression Profiles ◽  
Specific Treatment ◽  
Hub Genes ◽  
Ppi Networks

Abstract Background IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, and its diagnosis depends mainly on renal biopsy. However, there is no specific treatment for IgAN. Moreover, its causes and underlying molecular events require further exploration. Methods The expression profiles of GSE64306 and GSE93798 were downloaded from the Gene Expression Omnibus (GEO) database and used to identify the differential expression of miRNAs and genes, respectively. The StarBase and TransmiR databases were employed to predict target genes and transcription factors of the differentially expressed miRNAs (DE-miRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to predict biological functions. A comprehensive analysis of the miRNA-mRNA regulatory network was constructed, and protein–protein interaction (PPI) networks and hub genes were identified. CIBERSORT was used to examine the immune cells in IgAN, and correlation analyses were performed between the hub genes and infiltrating immune cells. Results Four downregulated miRNAs and 16 upregulated miRNAs were identified. Forty-five and twelve target genes were identified for the upregulated and downregulated DE-miRNAs, respectively. CDKN1A, CDC23, EGR1, HIF1A, and TRIM28 were the hub genes with the highest degrees of connectivity. CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN. Additionally, HIF1A, CDC23, TRIM28, and CDKN1A in IgAN patients were associated with immune cell infiltration. Conclusions A potential miRNA-mRNA regulatory network contributing to IgAN onset and progression was successfully established. The results of the present study may facilitate the diagnosis and treatment of IgAN by targeting established miRNA-mRNA interaction networks. Infiltrating immune cells may play significant roles in IgAN pathogenesis. Future studies on these immune cells may help guide immunotherapy for IgAN patients.

Local and Systemic Inflammatory Markers as Prognostic and Predictive Markers In Locally Advanced Triple Negative Breast Cancer

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 30-30
Author(s):  
Lamiss Mohamed ◽  
Aymn Elsaka ◽  
Yomna Zamzam
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Inflammatory Markers ◽  
Triple Negative ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Complete Response ◽  
P Value ◽  
Neutrophil Lymphocyte Ratio

Local inflammatory markers have been defined as prognostic and predictive markers in triple negative markers as proved by many studies. The prognostic and predictive value of systemic inflammatory markers such as neutrophil lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) remain to be elucidated. Aim of study: To evaluate pathological complete response (PCR) to neoadjuvant chemotherapy in locally advanced cancer breast in relation to tumor infiltrating lymphocytes(TILs), neutrophil lymphocyte ratio and lymphocyte monocyte ratio as well as overall survival and disease free survival. Patients and methods: In Tanta university Hospital, oncology department form January 2012 to December 2013, 67 patients with locally advanced TNBC stage IIB, IIIB 0r IIIC using TNM 8t h edition . All patients received neoadjuvant chemotherapy in the form of dose dense AC followed by paclitaxel (adriamycin & cyclophosphamide 60 mgm/m2 & 600 mgm/m2 respectively the cycle is repeated every 2 weeks for 4 cycles followed by paclitaxel 175mgm/m2 every 2 weeks for 4 cycles). All cycles with G-CSF support. Pre treatment TILs, NLR and LMR were evaluated with PCR and as prognostic factor of survival. Results: Low NLR has been detected in 74.6% of cases and has been associated with high TILs and this was statistically significant (p value=0.03). High LMR was observed in 80.6% of cases and correlated significantly with TILs (p value =0.003). Pathological CR was found to be associated with high TILs, low NLR and high LMR. In our study we evaluated the pre neoadjuvant systemic and local inflammatory markers as prognostic marker we found that in multivariate analysis, the lymphocyte monocyte ratio maintained their statistical significance with overall survival. While tumor infiltrating lymphocyte maintained their statistical significance as prognostic factors with overall survival and disease free survival. Conclusion: Systemic inflammatory markers can be used as marker of pathological complete response in locally advanced triple negative breast6 cancer with neoadjuvant chemotherapy.

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