scholarly journals Prognostic Value and Related Regulatory Networks of MRPL15 in Non-Small-Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yangyang Zeng ◽  
Yingying Shi ◽  
Lu Xu ◽  
Yulan Zeng ◽  
Xiao Cui ◽  
...  

BackgroundMitochondrial ribosomal protein L15 (MRPL15), a member of mitochondrial ribosomal proteins whose abnormal expression is related to tumorigenesis. However, the prognostic value and regulatory mechanisms of MRPL15 in non-small-cell lung cancer (NSCLC) remain unclear.MethodsGEPIA, ONCOMINE, Gene Expression Omnibus (GEO), UALCAN, Kaplan–Meier plotter, PrognoScan, LinkedOmics and GeneMANIA database were utilized to explore the expression and prognostic value of MRPL15 in NSCLC. Additionally, immune infiltration patterns were evaluated via ESTIMATE algorithm and TISIDB database. Furthermore, the expression and prognostic value of MRPL15 in lung cancer were validated via immunohistochemistry (IHC) assays.ResultsIn NSCLC, multiple cohorts including GEPIA, ONCOMINE and 8 GEO series (GSE8569, GSE101929, GSE33532, GSE27262, GSE21933, GSE19804, GSE19188, GSE18842) described that MRPL15 was up-regulated. Moreover, MRPL15 was notably linked to gender, clinical stage, lymph node status and the TP53 mutation status. And patients with high MRPL15 expression showed poor overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and relapse-free survival (RFS) in NSCLC. Then, functional network analysis suggested that MRPL15 participated in metabolism-related pathways, DNA replication and cell cycle signaling via pathways involving several kinases, miRNAs and transcription factors. Additionally, it was found that MRPL15 expression was negatively related to immune infiltration, including immune scores, stromal scores and several tumor-infiltrating lymphocytes (TILs). Furthermore, IHC results further confirmed the high MRPL15 expression and its prognostic potential in lung cancer.ConclusionsThese findings demonstrate that high MRPL15 expression indicates poor prognosis in NSCLC and reveal potential regulatory networks as well as the negative relationship with immune infiltration. Thus, MRPL15 may be an attractive predictor and therapeutic strategy for NSCLC.

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoshan Su ◽  
Ning Liu ◽  
Weijing Wu ◽  
Zhixing Zhu ◽  
Yuan Xu ◽  
...  

Abstract Background Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated. Methods We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR. Results The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC. Conclusions The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.


2021 ◽  
Author(s):  
Xiaoshan Su ◽  
Ning Liu ◽  
Weijing Wu ◽  
ZHIXING ZHU ◽  
Yuan Xu ◽  
...  

Abstract Background: Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated. Methods: We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR. Results: The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis status. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC. Conclusions: The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.


2021 ◽  
Author(s):  
Yong Zhou ◽  
Yongfei Fan ◽  
Ming Lou ◽  
Xiaoshuang Liu ◽  
Yifeng Mao ◽  
...  

Abstract Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. Non-SMC condensin I complex subunit G (NCAPG) plays a significant role in tumor development. This study aimed to analyse the prognostic value and immunotherapy of NCAPG in non-small cell lung cancer. We set up a tissue microarray (containing 140 NSCLC and 10 normal lung tissues) and performed immunohistochemistry to assess NCAPG expression in the tissues of 140 patients. The receiver operating characteristic curves showed the diagnostic value of NCAPG. The prognostic value of NCAPG in NSCLC was assessed using the univariate and multivariate Cox proportional hazards regression models and Kaplan–Meier plots. We analyzed the association between NCAPG and immune infiltration in NSCLC. In addition, NCAPG expression and the degree of immune infiltration were evaluated based on data from TIMER and cumulative survival probability, and gene set enrichment analysis (GSEA) of NACPG was performed. Based on the database analysis and immunohistochemistry, the NCAPG expression was upregulated in patients with lung cancer compared with para cancer controls (p < 0.001). Multifactorial analysis and Kaplan–Meier plots revealed that upregulation of NCAPG expression was an independent factor in the prognosis of NSCLC. Data from CIBERSORT showed a negative correlation between NCAPG and the expression of memory CD4T cells, CD8T cells, dendritic cells, macrophages, mast cells, and NK cells (p < 0.001). GSEA revealed that cell cycle, adhesion and proliferation were significantly enriched in samples with a high NCAPG expression. NCAPG is a novel biomarker of prognosis and is associated with immune cell infiltration in the tumor microenvironment. Thus, it can be a potential target in NSCLC treatment.


Lung Cancer ◽  
2004 ◽  
Vol 46 (1) ◽  
pp. 125-126
Author(s):  
Stefano Margaritora ◽  
Alfredo Cesario ◽  
Domenico Galetta ◽  
Venanzio Porziella ◽  
Silvia Sterzi ◽  
...  

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