scholarly journals Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4902
Author(s):  
Hoang Dang Khoa Ta ◽  
Wei-Jan Wang ◽  
Nam Nhut Phan ◽  
Nu Thuy An Ton ◽  
Gangga Anuraga ◽  
...  

In recent decades, breast cancer (BRCA) has become one of the most common diseases worldwide. Understanding crucial genes and their signaling pathways remain an enormous challenge in evaluating the prognosis and possible therapeutics. The “Like-Smith” (LSM) family is known as protein-coding genes, and its member play pivotal roles in the progression of several malignancies, although their roles in BRCA are less clear. To discover biological processes associated with LSM family genes in BRCA development, high-throughput techniques were applied to clarify expression levels of LSMs in The Cancer Genome Atlas (TCGA)-BRCA dataset, which was integrated with the cBioPortal database. Furthermore, we investigated prognostic values of LSM family genes in BCRA patients using the Kaplan–Meier database. Among genes of this family, LSM4 expression levels were highly associated with poor prognostic outcomes with a hazard ratio of 1.35 (95% confidence interval 1.21–1.51, p for trend = 3.4 × 10−7). MetaCore and GlueGo analyses were also conducted to examine transcript expression signatures of LSM family members and their coexpressed genes, together with their associated signaling pathways, such as “Cell cycle role of APC in cell cycle regulation” and “Immune response IL-15 signaling via MAPK and PI3K cascade” in BRCA. Results showed that LSM family members, specifically LSM4, were significantly correlated with oncogenesis in BRCA patients. In summary, our results suggested that LSM4 could be a prospective prognosticator of BRCA.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7522 ◽  
Author(s):  
Xiang Song ◽  
Chao Zhang ◽  
Zhaoyun Liu ◽  
Qi Liu ◽  
Kewen He ◽  
...  

Triple-negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Previous studies have demonstrated that some abnormal expression of non-coding RNAs including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely related to tumor cell proliferation, apoptosis, invasion, migration and drug sensitivity. However, the role of non-coding RNAs in the pathogenesis of TNBC is still unclear. In order to characterize the molecular mechanism of non-coding RNAs in TNBC, we downloaded RNA data and miRNA data from the cancer genome atlas database. We successfully identified 686 message RNAs (mRNAs), 26 miRNAs and 50 lncRNAs as key molecules for high risk of TNBC. Then, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with TNBC and constructed a competitive endogenous RNA (ceRNA) network of TNBC. Our series of analyses has shown that five molecules (TERT, TRIML2, PHBP4, mir-1-3p, mir-133a-3p) were significantly associated with the prognosis of TNBC, and there is a prognostic ceRNA sub-network between those molecules. We mapped the Kaplan–Meier curve of RNA on the sub-network and also suggested that the expression level of the selected RNA is related to the survival rate of breast cancer. Reverse transcription-quantitative polymerase chain reaction showed that the expression level of TRIML2 in TNBC cells was higher than normal. In general, our findings have implications for predicting metastasis, predicting prognosis and discovering new therapeutic targets for TNBC.


Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 726
Author(s):  
Hoang Dang Khoa Ta ◽  
Wan-Chun Tang ◽  
Nam Nhut Phan ◽  
Gangga Anuraga ◽  
Sz-Ying Hou ◽  
...  

Breast cancer (BRCA) is one of the most complex diseases and involves several biological processes. Members of the L-antigen (LAGE) family participate in the development of various cancers, but their expressions and prognostic values in breast cancer remain to be clarified. High-throughput methods for exploring disease progression mechanisms might play a pivotal role in the improvement of novel therapeutics. Therefore, gene expression profiles and clinical data of LAGE family members were acquired from the cBioportal database, followed by verification using the Oncomine and The Cancer Genome Atlas (TCGA) databases. In addition, the Kaplan-Meier method was applied to explore correlations between expressions of LAGE family members and prognoses of breast cancer patients. MetaCore, GlueGo, and GluePedia were used to comprehensively study the transcript expression signatures of LAGEs and their co-expressed genes together with LAGE-related signal transduction pathways in BRCA. The result indicated that higher LAGE3 messenger (m)RNA expressions were observed in BRCA tissues than in normal tissues, and they were also associated with the stage of BRCA patients. Kaplan-Meier plots showed that overexpression of LAGE1, LAGE2A, LAGE2B, and LAGE3 were highly correlated to poor survival in most types of breast cancer. Significant associations of LAGE family genes were correlated with the cell cycle, focal adhesion, and extracellular matrix (ECM) receptor interactions as indicated by functional enrichment analyses. Collectively, LAGE family members’ gene expression levels were related to adverse clinicopathological factors and prognoses of BRCA patients; therefore, LAGEs have the potential to serve as prognosticators of BRCA patients.


Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1436
Author(s):  
Jung-Yu Kan ◽  
Sin-Hua Moi ◽  
Wen-Chun Hung ◽  
Ming-Feng Hou ◽  
Fang-Ming Chen ◽  
...  

Hypersialylation caused by the overexpression of sialyltransferases (STs) is a common feature in cancer that is associated with several characteristics of tumorigenesis. Thus, identifying cancer-associated STs is critical for cancer therapy. However, ST screening has been frequently conducted in cell line models. In this study, we conducted a comprehensive analysis of STs in the clinical database and identified the STs related with the survival of breast cancer patients. RNA sequencing (RNA-Seq) data of 496 patients were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA). Of the eight mapped STs, ST3GAL5, and ST8SIA1 met the acceptable area under the curve (AUC) criteria for overall survival (OS). Using Kaplan–Meier methods, we determined that high expression of ST8SIA1 was associated with poor 10-year OS in all patients, triple-negative breast cancer (TNBC), and non-TNBC patients, and poor disease-free survival (DFS) rates particularly in TNBC. ST8SIA1 also had superior AUC values in terms of OS/DFS. High ST8SIA1 levels showed a higher risk for poor OS in different groups of patients and a higher risk for poor DFS particularly in TNBC. In summary, we conducted a comprehensive analysis of STs from the clinical database and identified ST8SIA1 as a crucial survival-related ST, which might be a potential therapeutic target for breast cancer and TNBC patients.


Epigenomics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1251-1266
Author(s):  
Siheng Lin ◽  
Rui Zhou ◽  
Dongqiang Zeng ◽  
Jiani Wu ◽  
Jianhua Wu ◽  
...  

Aim: To develop novel diagnostic tools that can predict the prognosis of gastric cancer. Material & methods: Using RNA expression data from The Cancer Genome Atlas and Gene Expression Omnibus, we established protein-coding RNAs-noncoding RNAs-tumor microenvironment type (PNM) scores, which contain signatures of tumor protein coding genes (P), tumor noncoding genes (N) and immune/stroma cells in tumor microenvironment (M) to predict the prognosis of gastric cancer. Results & conclusion: Based on PNM scores, gastric cancer patients were divided into three subgroups and Kaplan–Meier survival curves revealed significant differences among the subgroups (p < 0.001). Our study showed that the PNM scores could be used as a robust predicting tool for the prognosis of gastric cancer.


2021 ◽  
pp. 1-12
Author(s):  
Xixun Zhang

Breast cancer (BC) is an aggressive cancer with a high percentage recurrence and metastasis. As one of the most common distant metastasis organ in BC, lung metastasis has a worse prognosis than that of liver and bone. Therefore, it’s important to explore some potential prognostic markers associated with the lung metastasis in BC for preventive treatment. In this study, transcriptomic data and clinical information of BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Co-expression modules constructed by weighted gene co-expression network analysis (WGCNA) found the royal blue module was significantly associated with lung metastasis in BC. Then, co-expression genes of this module were analyzed for functional enrichment. Furthermore, the prognostic value of these genes was assessed by GEPIA Database and Kaplan-Meier Plotter. Results showed that the hub genes, LMNB and CDC20, were up-regulated in BC and had a worse survival of the patients. Therefore, we speculate that these two genes play crucial roles in the process of lung metastasis in BC, which can be used as potential prognostic markers in lung metastasis of BC. Collectively, our study identified two potential key genes in the lung metastasis of BC, which might be applied as the prognostic markers of the precise treatment in breast cancer with lung metastasis.


2021 ◽  
Author(s):  
Mingjie Li ◽  
Qianyun Wang ◽  
Qinqin Zheng ◽  
Lin Wu ◽  
Bin Zhao ◽  
...  

Aim: We aimed to evaluate the diagnostic and prognostic values of P4HAs in breast cancer (BC) patients. Materials & methods: Kaplan–Meier plotter was used to evaluate the prognostic values of P4HAs and correlations between their expression and clinical characteristics were assessed based on The Cancer Genome Atlas and the Human Protein Atlas. Results: The current study showed that P4HAs were highly expressed in BC patients with clinical stage I compared with nontumor control and elevated P4HAs were correlated with poor survival outcomes. Subtypes analysis revealed that P4HA1 and P4HA2 were most expressed in HER2+ subtypes patients. Univariate analysis displayed that elevated P4HA1 and P4HA3 correlated with unfavorable recurrence-free survival in mutated TP53 patients. Conclusion: This study indicated the diagnostic and prognostic roles of P4HAs members and broadened the biomarker fields of early diagnosis and prognostic monitoring of BC patients.


Author(s):  
Minhyeong Lee

This study aimed to rank cancers based on the strength of the relationship between the comprehensive mRNA expression levels of the most harmful or protective genes and patient survival. Using The Cancer Genome Atlas dataset that includes the RNA sequencing and c linical data, we investigated not only gene specific prognostic availability, but also comprehensive prognostic availability of prognostic genes filtered by the Cox coefficient values, and ranked cancers using a specially designed prognostic indicator. Usi ng Kaplan Meier plots, we found that cancers vary in the strength of the influence of their prognostic genes, and can be ranked based on this finding. There is a high probability that the treatment developed by using methods that reduce or increase the exp ression levels of biomarkers, for cancers that ranked at the bottom will not be efficient. The results of this study could be used as scientific evidence for the same.


Author(s):  
Shamim Mushtaq

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.


Epigenomics ◽  
2020 ◽  
Author(s):  
Qijie Zhao ◽  
Jinan Guo ◽  
Yueshui Zhao ◽  
Jing Shen ◽  
Parham Jabbarzadeh Kaboli ◽  
...  

Background: PD-L1 and PD-L2 are ligands of PD-1. Their overexpression has been reported in different cancers. However, the underlying mechanism of PD-L1 and PD-L2 dysregulation and their related signaling pathways are still unclear in gastrointestinal cancers. Materials & methods: The expression of PD-L1 and PD-L2 were studied in The Cancer Genome Atlas and Genotype-Tissue Expression databases. The gene and protein alteration of PD-L1 and PD-L2 were analyzed in cBioportal. The direct transcription factor regulating PD-L1/ PD-L2 was determined with ChIP-seq data. The association of PD-L1/PD-L2 expression with clinicopathological parameters, survival, immune infiltration and tumor mutation burden were investigated with data from The Cancer Genome Atlas. Potential targets and pathways of PD-L1 and PD-L2 were determined by protein enrichment, WebGestalt and gene ontology. Results: Comprehensive analysis revealed that PD-L1 and PD-L2 were significantly upregulated in most types of gastrointestinal cancers and their expressions were positively correlated. SP1 was a key transcription factor regulating the expression of PD-L1. Conclusion: Higher PD-L1 or PD-L2 expression was significantly associated with poor overall survival, higher tumor mutation burden and more immune and stromal cell populations. Finally, HIF-1, ERBB and mTOR signaling pathways were most significantly affected by PD-L1 and PD-L2 dysregulation. Altogether, this study provided comprehensive analysis of the dysregulation of PD-L1 and PD-L2, its underlying mechanism and downstream pathways, which add to the knowledge of manipulating PD-L1/PD-L2 for cancer immunotherapy.


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