scholarly journals Integrated Bioinformatic Analysis of the Expression and Prognosis of Caveolae-Related Genes in Human Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao Tian ◽  
Xiaofeng Liu ◽  
Jing Hu ◽  
Huan Zhang ◽  
Baichuan Wang ◽  
...  

Caveolae-related genes, including CAVs that encodes caveolins and CAVINs that encodes caveolae-associated proteins cavins, have been identified for playing significant roles in a variety of biological processes including cholesterol transport and signal transduction, but evidences related to tumorigenesis and cancer progression are not abundant to correlate with clinical characteristics and prognosis of patients with cancer. In this study, we investigated the expression of these genes at transcriptional and translational levels in patients with breast cancer using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal databases, and immunohistochemistry of the patients in our hospital. Prognosis of patients with breast cancer based on the expressions of CAVs and CAVINs was summarized using Kaplan-Meier Plotter with their correlation to different subtyping. The relevant molecular pathways of these genes were further analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and Gene Set Enrichment Analysis (GSEA). Results elucidated that expression levels of CAV1, CAV2, CAVIN1, CAVIN2, and CAVIN3 were significantly lower in breast cancer tissues than in normal samples, while the expression level of CAVIN2 was correlated with advanced tumor stage. Furthermore, investigations on survival of patients with breast cancer indicated outstanding associations between prognosis and CAVIN2 levels, especially for the patients with estrogen receptor positive (ER+) breast cancer. In conclusion, our investigation indicated CAVIN2 is a potential therapeutic target for patients with ER+ breast cancer, which may relate to functions of cancer cell surface receptors and adhesion molecules.

2021 ◽  
Vol 10 ◽  
Author(s):  
Wenhua Xu ◽  
Wenna Yang ◽  
Chunfeng Wu ◽  
Xiaocong Ma ◽  
Haoyu Li ◽  
...  

Enolase 1 (ENO1) is an oxidative stress protein expressed in endothelial cells. This study aimed to investigate the correlation of ENO1 with prognosis, tumor stage, and levels of tumor-infiltrating immune cells in multiple cancers. ENO1 expression and its influence on tumor stage and clinical prognosis were analyzed by UCSC Xena browser, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and GTEx Portal. The ENO1 mutation analysis was performed by cBio Portal, and demonstrated ENO1 mutation (1.8%) did not impact on tumor prognosis. The relationship between ENO1 expression and tumor immunity was analyzed by Tumor Immune Estimation Resource (TIMER) and GEPIA. The potential functions of ENO1 in pathways were investigated by Gene Set Enrichment Analysis. ENO1 expression was significantly different in tumor and corresponding normal tissues. ENO1 expression in multiple tumor tissues correlated with prognosis and stage. ENO1 showed correlation with immune infiltrates including B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells, and tumor purity. ENO1 was proved to be involved in DNA replication, cell cycle, apoptosis, glycolysis process, and other processes. These findings indicate that ENO1 is a potential prognostic biomarker that correlates with cancer progression immune infiltration.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-Yin Chen ◽  
Chien-Feng Li ◽  
Ching-Hua Yeh ◽  
Ming-Shi Chang ◽  
Chung-Hsi Hsing

Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL-) 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored bothin vitroandin vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.


2017 ◽  
Author(s):  
Lucy Ireland ◽  
Almudena Santos ◽  
Fiona Campbell ◽  
Carlos Figueiredo ◽  
Lesley Ellies ◽  
...  

ABSTRACTBreast cancer remains the leading cause of cancer death in women due to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumours. 75% of breast cancer patients show activation of Insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in a pre-clinical breast cancer model compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation.


2018 ◽  
Author(s):  
Bo Tang ◽  
Jilin Wu ◽  
Michael X. Zhu ◽  
Xuemei Sun ◽  
Jingjing Liu ◽  
...  

AbstractAlthough VPAC1 and its ligand vasoactive intestinal peptide (VIP) are important in gastrointestinal physiology, their involvements in progression of gastrointestinal tumor have not been explored. Here, we found that higher expression of VIP/VPAC1 was observed in gastric cancer compared to the adjacent normal tissues. The increased expression of VIP/VPAC1 in gastric cancer correlated positively with invasion, tumor stage, lymph node, distant metastases, and poor survival. Moreover, high expression of VIP and VPAC1, advanced tumor stage and distant metastasis were independent prognostic factors. VPAC1 activation by VIP markedly induced TRPV4-mediated Ca2+ entry, and eventually promoted gastric cancer progression in a Ca2+ signaling-dependent manner. Inhibition of VPAC1 and its signaling pathway could block the progressive responses. VPAC1/TRPV4/Ca2+ signaling in turn enhanced the expression and secretion of VIP in gastric cancer cells, enforcing a positive feedback regulation mechanism. Taken together, our study demonstrate that VPAC1 is significantly overexpressed in gastric cancer and VPAC1/TRPV4/Ca2+ signaling axis could enforce a positive feedback regulation in gastric cancer progression. VIP/VPAC1 may serve as potential prognostic markers and therapeutic targets for gastric cancer.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ben Ma ◽  
Tian Liao ◽  
Duo Wen ◽  
Chuanpeng Dong ◽  
Li Zhou ◽  
...  

Abstract A number of long non-coding RNAs (lncRNAs) have been found to play critical roles in oncogenesis and tumor progression. We aimed to investigate whether lncRNAs could act as prognostic biomarkers for papillary thyroid cancer (PTC) that may assist us in evaluating disease status and prognosis for patients. We found 220 lncRNAs with expression alteration from the annotated 2773 lncRNAs approved by the HUGO gene nomenclature committee in The Cancer Genome Atlas (TCGA) dataset, of which FAM41C, CTBP1-AS2, LINC00271, HAR1A, LINC00310 and HAS2-AS1 were associated with recurrence. After adjusting classical clinicopathogical factors and BRAF V600E mutation, LINC00271 was found to be an independent risk factor for extrathyroidal extension, lymph node metastasis, advanced tumor stage III/IV and recurrence in multivariate analyses. Additionally, LINC00271 expression was significantly downregulated in PTCs versus adjacent normal tissues (P < 0.001). The Gene Set Enrichment Analysis (GSEA) revealed that genes associated with cell adhesion molecules, cell cycle, P53 signaling pathway and JAK/STAT signaling pathway were remarkably enriched in lower-LINC00271 versus higher-LINC00271 tumors. In conclusion, LINC00271 was identified as a possible suppressor gene in PTC in our study, and it may serve as a potential predictor of poor prognoses in PTC.


Breast Cancer ◽  
2021 ◽  
Author(s):  
Patrick Lebok ◽  
Hannah Bönte ◽  
Martina Kluth ◽  
Christina Möller-Koop ◽  
Isabell Witzel ◽  
...  

Abstract Background Deletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration. Methods We made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysis Results Heterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade (p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity (p = 0.0182), high Ki67 proliferation index (p < 0.0001), amplifications of HER2 (p = 0.0159), CCND1 (p = 0.0069), and cMYC (p = 0.0411), as well as deletions of PTEN (p = 0.0003), 8p21 (p < 0.0001), and 9p21 (p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases. Conclusion Our data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.


2021 ◽  
pp. 1212-1219
Author(s):  
Melinda Mushonga ◽  
Anna Mary Nyakabau ◽  
Ntokozo Ndlovu ◽  
Hari Subramaniam Iyer ◽  
Jennifer Ruth Bellon ◽  
...  

PURPOSE In sub-Saharan Africa, radiotherapy (RT) utilization and delivery patterns have not been extensively studied in patients with metastatic breast cancer. METHODS A retrospective cohort study of female patients with metastatic breast cancer seen at Parirenyatwa Radiotherapy Centre in Zimbabwe from 2014 to 2018 was conducted. Demographics, pathology, staging, and treatment data were abstracted through chart review. Fisher's exact test and chi-squared test of independence were used to compare proportions, and independent two-sample t-tests were used to compare means. RESULTS Of 351 patients with breast cancer, 152 (43%) had metastatic disease, median age 51 years (interquartile range: 43-61 years). Of those with metastatic disease, 30 patients (20%) received radiation to various metastatic sites: 16 spine; three nonspine bone metastases; six whole brain; and five chest wall or supraclavicular. Patients who received radiation were younger (46 v 52 years; P = .019), but did not differ significantly by performance status than those who did not. The most common dose prescription was 30 Gy in 10 fractions (33%). Five (17%) patients had treatment interruption and two (7%) had treatment noncompletion. Province of origin and clinical tumor stage were significant predictors of RT receipt ( P = .002; and P = .018, respectively). CONCLUSION A minority of patients with metastatic breast cancer received RT (20%), and these were likely to be younger, with advanced tumor stage, and resided in provinces where RT is available. Conventional courses were generally prescribed. There is a need to strongly consider palliative RT as an option for patients with metastatic breast cancer and use of hypofractionated courses (e.g. 8 Gy in one fraction) may support this goal.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10128
Author(s):  
Mengxue Wang ◽  
Meng Dai ◽  
Yu-shen Wu ◽  
Ziying Yi ◽  
Yunhai Li ◽  
...  

Background Immunoglobulin superfamily member 10 (IGSF10) is a member of the immunoglobulin superfamily that is expressed at high levels in both the gallbladder and ovary. Currently, the role and possible mechanism of IGSF10 in breast cancer remain unclear. Method By applying real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), the expression of IGSF10 in breast cancer cells and tissues was detected. We collected the clinical information from 700 patients with breast cancer in The Cancer Genome Atlas (TCGA), and analyzed the relationship between IGSF10 expression and the clinicopathological features and survival outcomes of these patients. The potential mechanisms and pathways associated with IGSF10 in breast cancer were explored by performing a gene set enrichment analysis (GSEA). Results According to TCGA data, qRT-PCR and IHC experiments, levels of the IGSF10 mRNA and protein were significantly decreased in breast cancer tissues. IGSF10 expression was significantly correlated with age, tumor size, and tumor stage. Moreover, shorter overall survival (OS) and relapse-free survival (RFS) correlated with lower IGSF10 expression, according to the survival analysis. The multivariate analysis identified that IGSF10 as an independent prognostic factor for the OS (hazard ratio (HR) = 1.793, 95% confidence interval (CI) [1.141–2.815], P = 0.011) and RFS (HR = 2.298, 95% CI [1.317–4.010], P = 0.003) of patients with breast cancer. Based on the GSEA, IGSF10 was involved in DNA repair, cell cycle, and glycolysis. IGSF10 was also associated with the PI3K/Akt/mTOR and mTORC1 signaling pathways. Conclusions This study revealed a clear relationship between IGSF10 expression and the tumorigenesis of breast cancer for the first time. Therefore, further studies are needed to understand the mechanism of IGSF10 in breast cancer.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Ke-Yun Zhu ◽  
Yao Tian ◽  
Ying-Xi Li ◽  
Qing-Xiang Meng ◽  
Jie Ge ◽  
...  

Abstract Background Krüppel‐like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited. Methods We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro. Results The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis. Conclusions KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaomin Li ◽  
Junhe Gou ◽  
Hongjiang Li ◽  
Xiaoqin Yang

Abstract Chromobox (CBX) family proteins control chromatin structure and gene expression. However, the functions of CBXs in cancer progression, especially breast cancer, are inadequately studied. We assessed the significance of eight CBX proteins in breast cancer. We performed immunohistochemistry and bioinformatic analysis of data from Oncomine, GEPIA Dataset, bcGenExMiner, Kaplan–Meier Plotter, and cBioPortal. We compared mRNA and protein expression levels of eight CBX proteins between breast tumor and normal tissue. The expression difference of CBX7 was the greatest, and CBX7 was downregulated in breast cancer tissues compared with normal breast tissues. The expression of CBX2 was strongly associated with tumor stage. We further analyzed the association between the eight CBX proteins and the following clinicopathological features: menopause age, estrogen receptor (ER), progesterone receptor (PR) and HER-2 receptor status, nodal status, P53 status, triple-negative status, and the Scarff–Bloom–Richardson grade (SBR) and Nottingham prognostic index (NPI). Survival analysis in the Kaplan–Meier Plotter database showed that the eight CBX proteins were significantly associated with prognosis. Moreover, CBX genes in breast cancer patients had a high net alteration frequency of 57%. There were significant co-expression correlations between the following CBX protein pairs: CBX4 positively with CBX8, CBX6 positively with CBX7, and CBX2 negatively with CBX7. We also analyzed the Gene Ontology enrichment of the CBX proteins, including biological processes, cellular components, and molecular functions. CBX 1/2/3/5/8 may be oncogenes for breast cancer, whereas CBX 6 and 7 may be tumor suppressors for breast cancer. All eight CBX proteins may be predictive for prognosis. Clinical trials are needed to confirm the significance of the eight CBX proteins in breast cancer.


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