
Rongrong WuTokyo Medical University | TMU · Division of Breast Oncology
Rongrong Wu
Doctor of Medicine
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70
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Publications
Publications (70)
Background: Peritumoral lidocaine infiltration prior to excision is associated with better survival in breast cancer (BC), which led us to hypothesize that innervation to the tumor affects its biology and patient survival. Activity-regulated cytoskeleton-associated protein (ARC) gene expression is known to be regulated by neuronal activity. Therefo...
Background: Vascular endothelial growth factor-A (VEGFA) is a key inducer of angiogenesis, responsible for generating new blood vessels in the tumor microenvironment (TME) and facilitating metastasis. Notably, Avastin, which targets VEGFA, failed to demonstrate any significant benefit in clinical trials for breast cancer (BC). This study aimed to i...
Triple negative breast cancer (TNBC) is one of the deadliest subtypes of breast cancer, whose high frequency of relapse is often due to resistance to chemotherapy. Here, we identify inosine monophosphate dehydrogenase 2 (IMPDH2) as a contributor to doxorubicin resistance, in multiple TNBC models. Analysis of publicly available datasets reveals elev...
Background
We aimed to clarify the features of adolescents and young adults (AYA: younger than 40 years old) breast cancer (BC) compared with other age groups in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC, given the effects of age-related hormonal status.
Methods
The cohorts analyzed were divided in...
Intratumoral genomic heterogeneity (ITGH), the existence of genotypic and phenotypic variation within an individual tumor, is known to be a key mechanism in treatment resistance. Deviating gene Expression Profiling Tumor Heterogeneity 2 (DEPTH2) algorithm was developed to estimate ITGH using solely RNA expression data unlike the others that require...
Objective
To investigate the clinical relevance of common myeloid progenitor (CMP) cells in breast tumor microenvironment (TME).
Background
The role of rare cells in TME is less studied. In Silico transcriptomic analyses of real-world data enable us to detect and quantify rare cells, including CMP cells.
Methods
Total of 5,176 breast cancer (BC)...
Background: Intratumor heterogeneity (ITH) refers to the presence of distinct cancer cell populations with different clones within a single tumor mass. Tumors with high ITH are more prone to progression, exhibit resistance to therapies, and are associated with an unfavorable prognosis. Therefore, evaluation of ITH is anticipated to serve as a break...
Tumor-infiltrating lymphocytes are a general term for lymphocytes or immune cells infiltrating the tumor microenvironment. Numerous studies have demonstrated tumor-infiltrating lymphocytes to be robust prognostic and predictive biomarkers in breast cancer. Recently, immune checkpoint inhibitors, which directly target tumor-infiltrating lymphocytes,...
Background
We aimed to clarify the features of adolescents and young adults (AYA: younger than 40yo) breast cancer (BC) compared with other age groups in ER-positive/HER2-negative BC, given the effects of age-related hormonal status.
Methods
The cohorts analyzed were divided into: AYA (15-39yo), Perimenopausal (40-54yo), Menopausal (55-64yo), and...
Background
Determining the prognosis of hormone receptor positive (HR⁺) breast cancer (BC), which accounts for 80% of all BCs, is critical in improving survival outcomes. Stratifying individuals at high risk of BC-related mortality and improving prognosis has been the focus of research for over a decade. However, these tools are not universal as th...
Metabolic reprogramming to sustain immortality is a hallmark of cancer and glycolysis is an important way to attain this. Thus, we investigate the association of glycolysis and associated pathways in the survival of breast cancer. A total of 5,176 breast cancer patients from multiple independent cohorts were analyzed. We determined the glycolytic s...
Autotaxin (ATX) is a secreted enzyme that produces extracellular lysophosphatidate in physiological wound healing. ATX is overexpressed in many cancers to promote growth, metastasis, and treatment resistance. However, ATX expression is very low in breast cancer cells, and is instead secreted by the tumor microenvironment (TME). Paracrine ATX expres...
Simple Summary
Breast cancer (BC) in adolescents and young adults (AYA) has unique biological qualities, but the details of these features remain unclear, and treatment options are comparable to those of other age groups. In this study, we identified a gene that demonstrates a strong association with patient prognosis solely in AYA patients, despit...
Objective:
To investigate the clinical relevance of intratumoral tumor infiltrating lymphocytes (TILs) in breast cancer as measured by computational deconvolution of bulk tumor transcriptomes.
Summary background:
Commonly assessed TILs, located in tumor stroma without direct contact with cancer cells (stromal TILs), correlate with breast cancer...
Lysophosphatidic acid receptors (LPARs) are six G-protein-coupled receptors that mediate LPA signaling to promote tumorigenesis and therapy resistance in many cancer subtypes, including breast cancer. Individual-receptor-targeted monotherapies are under investigation, but receptor agonism or antagonism effects within the tumor microenvironment foll...
The LPP family is comprised of three enzymes that dephosphorylate bioactive lipid phosphates both intracellularly and extracellularly. Pre-clinical breast cancer models have demonstrated that decreased LPP1/3 with increased LPP2 expression correlates to tumorigenesis. This though has not been well verified in human specimens. In this study, we corr...
Introduction: Abundance of tumor infiltrated lymphocytes (TILs) in the peripheral region of tumor assessed pathologically is associated with improved response to chemotherapy and better prognosis in Her2+ and triple-negative breast cancer (TNBC). Since recent progress in bioinformatics has allowed for computational deconvolution of bulk tumor, we i...
Introduction: Tumor infiltrating lymphocytes are well known as an important component in the microenvironment in human cancers, including breast cancer tumors. Not only tumor infiltrating T cells, but B cells have been recognized as a new hallmark of cancer immunity. However, the roles of each B cell subset remain unclear. We investigated the breas...
Background: Epithelial-mesenchymal transition (EMT) is a well-known multistep process of cancer cell invasion and metastasis, as well as treatment resistance. Our group has been reporting the predictive role of scores generated using Gene Set Variation Analysis (GSVA) of Hallmark pathways in breast cancer. In this study, we hypothesized that EMT sc...
MicroRNA (miRNA) are known as a key player in tumor biology and is shown to epigenetically regulate a large number of protein-coding genes, including tumor-related genes. MiR-150, a hematopoietic cell-specific miRNA, has been suggested to have various effects on cell proliferation, differentiation, apoptosis, migration, and invasion. However, there...
Background: MicroRNA (miR) is single stranded RNA which regulates the gene expression epigenetically by inhibiting the mRNA translation as well as promoting mRNA degradation. MiR-99b is known as a regulator of mechanistic target of rapamycin (mTOR) signaling and was reported as both onco-miR that promote cell proliferation and tumor suppressor-miR...
INTRODUCTION: Abundance of tumor infiltrating lymphocytes (TILs) is well known to be associated with achievement of pathologic complete response (pCR) after neoadjuvant chemotherapy and is a surrogate of better survival in triple negative breast cancer (TNBC). However, the association remains unclear in ER-positive/HER2-negative, which is the most...
Introduction: Highly proliferative cancers are known to respond better to neoadjuvant chemotherapy (NAC), and pathological complete response (pCR) is a surrogate for survival benefit in breast cancer. Ki67 is the most commonly used cell proliferation marker; however, conventional immunostaining is subjected to variability by the assessor and the in...
Outcomes in pancreatic ductal adenocarcinoma (PDAC) are known to be worse in tumors with high integrin β1 expression, but targeted monotherapy against this integrin has not been effective. Seven other beta integrins are expressed in mammalian biology and they are known to have overlapping and compensatory signaling in biological systems. However, t...
The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of t...
Background
Pancreatic cancer (PC) has an extremely high mortality rate, where obstructive jaundice due to cholestasis is a classic symptom. Conjugated bile acids (CBAs) such as taurocholic acid (TCA) have been reported to activate both the ERK1/2 and AKT signaling pathways via S1P receptor 2 (S1PR2) and promote growth of cholangiocarcinoma. Thus, w...
Bile acids are metabolized by the gut microbiome and are involved in fat absorption. Contrary to their carcinogenic role in gastrointestinal cancers, bile acids have been reported to inhibit cancer cell proliferation in breast cancer. The microbiome of breast cancer tissues may also influence cancer proliferation. We hypothesized that bile acid met...
Background
BRCAness is a characteristic feature of homologous recombination deficiency (HRD) mimicking BRCA gene mutation in breast cancer. We hypothesized that a measure to quantify BRCAness that causes synthetic lethality in BRCA mutated tumors will identify responders to PARP inhibitors.
Methods
A total of 6753 breast cancer patients from 3 lar...
Although miR-99b is a known suppressive microRNA (miRNA) in several cancers, its role in breast cancer has not been elucidated. In this study, we examined the clinical relevance of miR-99b expression in breast cancer. We analyzed miRNA and mRNA expression and their relationships with clinical parameters in 1,961 breast cancer samples from two indep...
Background: Although miR-99b is a known suppressive microRNA in several cancer types, its role in breast cancer is not elucidated. In this study, we examine the clinical relevance of miR-99b expression in breast cancer.
Methods: We analyzed microRNA and messenger RNA expressions and their relationships with clinical parameters for 1,961 breast canc...
Purpose:
Platelet-derived growth factor B (PDGFB) is known to play essential roles in angiogenesis and lymphangiogenesis during development, and tumor growth and vessel stabilization in experimental models. However, whether these findings could be translated to breast cancer patients remains unclear. We hypothesized that PDGFB gene expression is a...
Although the value of tumor-infiltrating lymphocytes is well known, the clinical relevance of an increased immune response, specifically in breast cancer, has not been investigated across large cohorts of patients using computational algorithms. Our hypothesis stated that an enhanced immune response is associated with an improvement in outcomes. To...
Despite low mutational burden, immune checkpoint inhibitors have demonstrated promising results in a significant minority of hepatocellular carcinoma (HCC) patients with advanced disease. We hypothesized that HCC patients with higher levels of CD8+ T cell infiltration reflect an immune-inflamed cohort which has improved oncologic outcomes. 355 HCC...
Purpose
Reactive oxygen species (ROS) are oxygen-containing molecules that have high reactivity and play roles in protection or harm the cancer cells. We aimed to clarify the clinical relevance of ROS in breast cancer (BC) tumor microenvironment (TME). We hypothesized that it is associated with worse BC patient outcomes.
Methods
ROS score was gene...
BACKGROUND: Bile acids are generated and secreted by hepatocytes and are involved in intestinal circulation. Recently it has been reported that specific bile acids are accumulated in the breast cancer tumor microenvironment (TME), leading to a favorable prognosis for patients and reducing the aggressiveness and metastatic potential of the cancer. W...
Background: Bleeding is one of the most commonly observed clinical signs of gastrointestinal cancer. Coagulation regulates inflammation and angiogenesis in cancer, and is associated with tumor development and metastasis. To date, there has been no measures to quantify the state of intra-tumoral coagulation. We hypothesized that intra-tumoral coagul...
Background: Within the tumor microenvironment, regulatory T cells (Tregs) are potent facilitators of immune tolerance, and in most solid tumors a higher proportion of Tregs compared to cytotoxic T cells predicts a worse outcome. However, the role of Tregs in colorectal cancer (CRC) is more controversial, possibly due in part to the effect of the gu...
Aberrant expression of certain cancer-promoting genes is the associative factor of metastasis and cancer-related death. Autophagy is a highly conserved catabolic process that can be regulated by starvation or stress. Among several cellular stresses, hypoxia and nutrient stress can strongly activate autophagy-related genes. Autophagy plays dual role...
Dysregulated miRNAs play key roles in multiple biological processes and cancer. miR-150-5p, a cancer-related miRNA, has been reported to be aberrantly expressed in various cancers. We found that triple-negative and HER2+ breast cancer patients have elevated expression of miR150 in the TCGA and METABRIC patient cohort. Both cohorts showed significan...
INTRODUCTION: Homologous recombination deficiency (HRD) is involved in breast cancer carcinogenesis, however, activation of DNA repair in cancer cells may promote its survival and progression. RAD51 plays an essential role in homologous recombination with BRCA2. Recently, RAD51 has been highlighted to play a role in resistance to DNA-damaging chemo...
Background: Protein homeostasis as regulated by the Endoplasmic Reticulum (ER) is a recognized process involved in cancer progression. ER stress activates the Unfolded Protein Response (UPR) and has been implicated in a variety of cancers. Due to the exposure of chronic stressors, cancer cells learn to adapt to prolonged ER stress by creating pro-s...
Background:
Tumor dormancy is a crucial mechanism responsible for the late recurrence of breast cancer. Thus, we investigated the clinical relevance of the expression of NR2F1, a known dormancy biomarker.
Methods:
A total of 6758 transcriptomes of bulk tumors from multiple breast cancer patient cohorts and two single-cell sequence cohorts were a...
The sialyltransferase ST6GAL1 that adds α2–6 linked sialic acids to N-glycans of cell surface and secreted glycoproteins is prominently associated with many human cancers. Tumor-native ST6GAL1 promotes tumor cell behaviors such as invasion and resistance to cell stress and chemo- and radio-treatments. Canonically, ST6GAL1 resides in the intracellul...
549
Background: BRCAness is a generic term used to describe characteristic features of homologous recombination deficiency (HRD) mimicking mutations in BRCA genes. Although clinical genetic testing has increased the detection of mutations in BRCA1 and BRCA2, we hypothesized that a measure to quantify BRCAness will identify the responders to PARP in...
e12539
Background: Bile acids are metabolized by the gut microbiome and are involved in fat absorption. Contrary to their carcinogenic role in gastrointestinal cancers, bile acids have been reported to inhibit cancer cell proliferation in breast cancer. We hypothesized that activation of bile acid metabolism is associated with a better prognosis ba...
e12550
Background: It is now well accepted that some cancer cells remain in quiescent state and survive through adjuvant systemic treatments, also known as tumor dormancy, which preserve the potential for late recurrence. NR2F1 is a known biomarker for dormant cancer cells, which suppress cell proliferation in experimental models. Here, we hypothes...
570
Background: MicroRNA (miRNA) epigenetically regulate a large number of cancer-related genes and is known as a key player in cancer biology. MiR-150 promote cancer cell proliferation, migration, and invasion. However, there has been no study that investigated the role of miR-150 in the tumor microenvironment (TME) of breast cancer patients. Meth...
Purpose
Estrogen signals play an important role in the phenotype of estrogen receptor-positive breast cancer. However, comprehensive analyses of the effect of responsiveness to estrogen signals on the tumor microenvironment and survival in large cohorts of primary breast cancer patients have been lacking. We aimed to test the hypothesis that estrog...
Purpose
Although the DNA repair mechanism is important in preventing carcinogenesis, its activation in established cancer cells may support their proliferation and aggravate cancer progression. RAD51 cooperates with BRCA2 and is essential in the homologous recombination of DNA repair. To this end, we hypothesized that RAD51 gene expression is assoc...
Purpose: Reactive oxygen species (ROS) are oxygen-containing molecules that have high reactivity and play roles in protection or harm the cancer cells. We aimed to clarify the clinical relevance of ROS in breast cancer (BC) tumor microenvironment (TME). We hypothesized that it is associated with worse BC patient outcomes.
Methods: ROS score was ge...
Background: Tripartite motif-containing protein 37 (TRIM37) is an oncogenic histone H2A ubiquitin ligase that is overexpressed in a subset of breast cancers. TRIM37 was suggested to be associated with chemotherapy resistance and metastasis of triple-negative breast cancer (TNBC) in in vivo and in vitro studies. Breast cancer with TRIM37 amplificati...
Background: Reactive oxygen species (ROS) in tumor microenvironment are known to promote many aspects of cancer progression. On the other hand, excessive accumulation of ROS can induce cancer cell apoptosis. To our knowledge, clinical relevance of ROS response signaling in breast cancer has never been studied in multiple large patient cohorts. Here...
In experimental settings, maternal embryonic leucine zipper kinase (MELK), an apical member of the snf1/AMPK serine-threonine kinases family, is highly expressed in several malignancies, and plays a role in cell cycle and proliferation in cell culture settings. However, there is no clear insight on the underlying mechanism or association of MELK ex...
Germline mutations in the loci of BRCA1 or BRCA2 genes with loss of heterozygosity or additional somatic truncation at the WT allele in breast cancer result in characteristic clinicopathological features of homologous recombination deficiency, also known as “BRCAness.”. Although clinical genetic testing for mutations of BRCA1 and BRCA2 has increase...
Epidermal growth factor receptor (EGFR) is one of the receptors that belongs to the epidermal growth factor family of receptor tyrosine kinases (ErbBs). Several malignancies including breast cancer that express EGFR have poor prognosis. Our study examined the EGFR expression among 5176 breast cancer patients from multiple independent breast cancer...
Background: The Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) cytidine deaminases subfamily has been a focus of attention as a cause of characteristic somatic mutations in breast cancer. APOBEC3A and APOBEC3B are known to be the key mutation drivers in breast cancer, while the other APOBEC3 family members have been implic...
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) causes a point mutation from cytidine to uracil in DNA and/or RNA. The role of APOBEC3A and APOBEC3B in breast cancer has been well described, whereas that of APOBEC3F remains unknown. To investigate the clinical relevance of APOBEC3F expression, we analyzed a total of 300...
Lymphangiogenesis, the generation of new lymphatic vessels from existing ones, results from the dynamic interactions of lymphatic endothelial cells and the tumor microenvironment (TME). It is well known that lymphangiogenesis occurs during the initial stage of metastasis in various types of malignant tumors. However, it is currently not used as a b...
Regulatory T cells (Tregs) are a subset of CD4+ T lymphocytes known to dampen the host immune response against cancer cells. Within the tumor microenvironment, Tregs are potent facilitators of immune tolerance, and a higher proportion of Tregs compared to cytotoxic T cells predicts a worse outcome in most solid tumors. We studied the association be...
Background: Unfavorable vasculogenesis, such as lymphangiogenesis and hemoangiogenesis are known to be pivotal of cancer progression. Our group reported that S1P pathway link chronic inflammation, such as obesity, and cancer progression by inducing lymphangiogenesis and hemoangiogenesis in breast cancer. During the past decade, complex cytokine net...
MicroRNA (miRNA) are known as a key player in tumor growth, and is shown to epigenetically regulate a large number of protein-coding genes, including tumor-related genes. MiR-150, a hematopoietic cell-specific miRNA, has been suggested to have various effects on cell proliferation, differentiation, apoptosis, migration, and invasion. However, there...
Metaplastic breast cancer (MBC) constitutes a rare but unique histologic entity with poor prognosis. We hypothesized that MBC possesses unique genetic profile and tumor immune microenvironment. MBC cases were identified from a total of 10827 breast cancer entries in the Cancer Genome Atlas Data Set (TCGA) and the AACR-GENIE (Genomics Evidence Neopl...
Purpose: Although DNA repair mechanism is a key to prevent carcinogenesis, its activation in established cancer cells may support their proliferation and aggravate cancer progression. RAD51 cooperates with BRCA2 and is essential in the homologous recombination of DNA repair. To this end, we hypothesized that RAD51 gene expression is associated with...
A 52-year-old woman with a strong family history of breast cancer was diagnosed as having triple-negative breast cancer (TNBC) in her right breast. Neoadjuvant chemotherapy (NAC; four cycles of epirubicin/cyclophosphamide/5-fluorouracil) was performed, followed by breast-conserving surgery and axillary lymph node dissection. Histopathological analy...