scholarly journals The tumor microbiome is implicated in breast cancer prognosis

2020 ◽  
Author(s):  
Jia Zhu ◽  
Jie Wu ◽  
Changgan Mo ◽  
Siyuan Liang ◽  
Tao Lian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Alpha Diversity ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Rrna Gene ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
Tumor Tissues ◽  
Tumor Immune Microenvironment

Abstract Background: Some breast cancer patients are prone to recurrence and metastasis. Increasing evidence suggests that the breast tissue contains a diverse population of bacteria, which may be modulating the risk of breast cancer development or progression. However, the extent of microbial contribution to the tumor immune microenvironment in breast cancer remains unknown. Here, we explored the potential influence of the tumor microbiota on the local immune microenvironment and breast cancer prognosis.Methods: Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition and identified bacteria that were differentially abundant between breast cancer patients with recurrence or metastasis (R/M) and those without recurrence or metastasis (NRM). We performed total RNA sequencing in tumor tissues from patients in both groups to determine differentially expressed genes (DEGs). The landscape of tumor-infiltrating immune cells (TIICs) subtypes in the tumor immune microenvironment was analyzed using CIBERSORT, based on the gene expression profiling of tumor tissues. Differences in the tumor microbiomes were then correlated with DEGs and differences in TIICs, in order to determine how microbial abundance may contribute to cancer progression.Results: Microbial alpha-diversity was higher in NRM patients than in R/M patients. The composition and functions of the tumor microbiome communities differed between the two groups. We found higher alpha-diversity, higher abundance of Ruminococcus, Butyrivibrio, and Deinococcus, and lower abundance of Microbacterium could serve as a predictor of better prognosis in breast cancer patients. We also found that 16 genes, including CD36, showed differential expression in NRM compared to R/M, and differences in the composition of TIICs were observed between the two groups. In addition, we observed that the different tumor microbiome profiles were associated with DEGs and differences in TIICs between the two groups.Conclusions: The tumor microbiome may affect the prognosis of breast cancer patients by influencing the tumor immune microenvironment. Thus, the tumor microbiome may be a useful prognostic indicator.

Can Intratumoral neutrophil lymphocyte ratio (NLR) be a prognostic biomarker in breast cancer patients?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12573-e12573
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Vijayashree Murthy ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
High Group ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12573 Background: In breast cancer patients, it is well known that the elevation of neutrophil lymphocyte ratio (NLR) in the blood are reported to associate with poor prognosis based on the notion that neutrophils represent pro-cancer, and lymphocytes represent anti-cancer immune cells. Tumor immune microenvironment has been demonstrated to play critical roles in the outcome of breast cancer patients. However, there is scarce evidence on the clinical relevance of intratumoral NLR in breast cancer patients. In the current study, we hypothesized that intratumoral NLR high tumors are associated with worse survival particularly in TNBC that is known to have high immune cell infiltration. Methods: A total of 1904 breast cancer patients’ data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) and analyzed. NLR was calculated by the gene expressions of CD66b (CEACAM8) and CD8 (CD8A). NLR high and low were divided by the median. Overall Survival (OS) and Disease-Free Survival were calculated utilizing Kaplan Meier method between intratumoral NLR high and low groups. xCell algorithm was used to analyze the infiltrated immune cells within the tumor immune microenvironment as we have previously published. Results: Intratumoral NLR high group was associated with worse OS in whole, ER-positive/HER2-negative, and triple negative (TN) subtypes, in agreement with the previous studies. TN subtype alone demonstrated worse DFS of NLR high group. Surprisingly, gene set enrichment analysis (GSEA) demonstrated no gene set enrichment to NLR high group, which implicates that there is no distinctive mechanism that associate with worse survival. Whereas, immune response-related gene sets significantly enriched to NLR low group in TN subtype. This enrichment was consistent in ER-positive/HER2-negative. Compared with ER-positive/HER2-negative subtype, anti-cancer immune cells such as CD4+ T cells, CD8+ T cells, M1 macrophage, and helper T helper type 1 cells were significantly infiltrated in TN patients (p < 0.001 for all genes), where M2 macrophages and neutrophils were less and regulatory T cells and T helper type 2 cells were more infiltrated in TN subtype. Furthermore, intratumoral NLR was significantly lower in TN compared with ER-positive/HER2-negative subtype (p < 0.001). These results suggest that intratumoral NLR low group is associated with better survival due to favorable tumor immune microenvironment in TN subtype rather than NLR high group has worse survival. Conclusions: Intratumoral NLR low tumor demonstrated more favorable OS and more favorable DFS in TN patients. Intratumoral NLR low breast cancer was associated with enhanced immune response and higher infiltration of anti-cancer immune cells were observed in TN subtype compared to ER-positive/HER2-negative which may contribute to the favorable outcome of in TN breast cancer.

Clinical relevance of miR-143 expression in ER-positive breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12574-e12574
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
Manabu Futamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
High Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12574 Background: MicroRNA-143(miR-143) is a well-known tumor suppressive microRNA in various malignancies, including breast cancer. Recently, the tumor immune microenvironment has been reported to associate with progression of breast cancers. However, the association with the tumor immune microenvironment and miR-143 in breast cancers remains ambiguous. Given these backgrounds, we hypothesized that high expression of miR-143 is associated with favorable effect to the tumor immune microenvironment which leads to better survival of ER positive breast cancer patients. Methods: Two major publicly available breast cancer cohorts were used for this study. A total of 753 patients from The Cancer Genome Atlas (TCGA) and total of 1283 patients from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. Results: We defined the higher quartile of miR-143 expression levels as high and the remainder as low expression groups. There was no significant difference in patient clinicopathlogical features between two groups. Gene set enrichment analysis (GSEA) revealed that miR-143 high expression tumors enriched Helper T cell type 1 (Th1) related gene sets indicating the upregulation of anti-cancer immune cells. Also, the cell composition of anti-cancer immune cells, such as Th1 and Macrophage M1 were higher with miR-143 high tumors (p < 0.001 and p < 0.01 respectively) in whole group. On the contrary, pro-cancer immune cells such as Th2 and M1 were lower with miR-143 high tumors (p < 0.01 and p < 0.001 respectively) in whole group. Interestingly, among the subtypes, we found that ER positive subgroup followed this trend of high infiltration rate of anti-cancer immune cells and low infiltration rate of pro-cancer immune cells. Furthermore, only ER positive subgroup demonstrated the survival benefit with miR-143 high expression tumors. Conclusions: We demonstrated that high expression of miR-143 in ER breast cancer associate with favorable tumor immune microenvironment, upregulation of the anti-cancer immune cells and suppression of the pro-cancer immune cells, and associate with better survival of the breast cancer patients.

scholarly journals Association between SNPs within MicroRNA Binding Sites and the Prognosis of Breast Cancer

2020 ◽  
Author(s):  
Liwen Zhang ◽  
Lu Han ◽  
Yubei Huang ◽  
Ziwei Feng ◽  
Xin Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Binding Sites ◽  
Cox Regression ◽  
Breast Cancer Prognosis ◽  
Stage I ◽  
Cancer Prognosis ◽  
Stage Ii ◽  
Breast Cancer Patients ◽  
Survival Times

Abstract Background: Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to the prognosis of cancer. We performed this study to explore the association between SNPs within microRNA binding sites and the prognosis of breast cancer.Methods: We carried out a two-stage study including 2647 breast cancer patients, with a median follow-up of 68 months (range 0-159). In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs significantly associated with breast cancer prognosis in another dataset using the TaqMan platform. Survival times was calculated, and Kaplan-Meier curves and Cox regression model were used to analyze survival of breast cancer patients with different genotypes.Results: We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (P<0.05), and only rs10878441 was statistically significant in stage II (AA vs CC: adjusted HR=2.21, 95% CI: 1.11-4.42, P=0.024). We combined the data from stage I and stage II, and found that, compared with rs10878441 AA genotype, CC genotype was significantly associated with poor survival of breast cancer (HR=1.69, 95% CI: 1.18-2.42, P=0.004; adjusted HR=2.19, 95% CI: 1.30-3.70, P=0.003). Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II patients and lymph node-negative patients (P<0.05).Conclusions: The LRKK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population, and it could be used as a potential prognostic biomarker for breast cancer. Further studies are warranted.

Exploratory Data Analysis on Breast Cancer Prognosis

2018 ◽  
pp. 1794-1805
Author(s):  
Mohammad Mehdi Owrang O. ◽  
Yasmine M. Kanaan ◽  
Robert L. Copeland Jr. ◽  
Melvin Gaskins ◽  
Robert L. DeWitty Jr.
Keyword(s):  
Breast Cancer ◽  
Marital Status ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Howard University ◽  
Kaplan Meier ◽  
Seer Data

Breast cancer prognosis is a vital element of providing effective treatment for breast cancer patients. Breast cancer prediction survivability has mainly been studied based on pathological factors such as tumor size, tumor grade, number of positive lymph nodes, and hormone receptors among others. This chapter looks at the significance of the non-clinical prognostic factors of age, ethnicity, and marital status in finding the prognosis for breast cancer patients. The National Cancer Institute's SEER data and the Howard University Cancer Center Tumor Registry data are analyzed. Prognostic tool NPI (Nottingham Prognostic Index) and survival analysis tools of Cox proportional hazards and Kaplan-Meier survival curve are used in analyzing the experiments. The results suggest that age, ethnicity, and marital status have some influence on the survivability rate of breast cancer patients.

scholarly journals High Expression of microRNA-143 is Associated with Favorable Tumor Immune Microenvironment and Better Survival in Estrogen Receptor Positive Breast Cancer

2020 ◽  
Vol 21 (9) ◽  
pp. 3213 ◽  
Author(s):  
Yoshihisa Tokumaru ◽  
Mariko Asaoka ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Li Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
High Expression ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive ◽  
Positive Breast Cancer

microRNA-143 (miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral function by targeting KRAS signaling pathways in various malignancies. We hypothesized that miR-143 suppresses breast cancer progression by targeting KRAS and its effector molecules. We further hypothesized that high expression of miR-143 is associated with a favorable tumor immune microenvironment of estrogen receptor (ER)-positive breast cancer patients which result in improved survival. Two major publicly available breast cancer cohorts; The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. The miR-143 high expression group was associated with increased infiltration of anti-cancer immune cells and decreased pro-cancer immune cells, as well as enrichment of the genes relating to T helper (Th1) cells resulting in improved overall survival (OS) in ER-positive breast cancer patients. To the best of our knowledge, this is the first study to demonstrate that high expression of miR-143 in cancer cells associates with a favorable tumor immune microenvironment, upregulation of anti-cancer immune cells, and suppression of the pro-cancer immune cells, associating with better survival of the breast cancer patients.

Exploratory Data Analysis on Breast Cancer Prognosis

2019 ◽  
pp. 367-380
Author(s):  
Mohammad Mehdi Owrang O. ◽  
Yasmine M. Kanaan ◽  
Robert L. Copeland Jr. ◽  
Melvin Gaskins ◽  
Robert L. DeWitty Jr.
Keyword(s):  
Breast Cancer ◽  
Marital Status ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Howard University ◽  
Kaplan Meier ◽  
Seer Data

Breast cancer prognosis is a vital element of providing effective treatment for breast cancer patients. Breast cancer prediction survivability has mainly been studied based on pathological factors such as tumor size, tumor grade, number of positive lymph nodes, and hormone receptors among others. This chapter looks at the significance of the non-clinical prognostic factors of age, ethnicity, and marital status in finding the prognosis for breast cancer patients. The National Cancer Institute's SEER data and the Howard University Cancer Center Tumor Registry data are analyzed. Prognostic tool NPI (Nottingham Prognostic Index) and survival analysis tools of Cox proportional hazards and Kaplan-Meier survival curve are used in analyzing the experiments. The results suggest that age, ethnicity, and marital status have some influence on the survivability rate of breast cancer patients.

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