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

Abstract

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.

FOXM1/lncRNA TYMSOS/miR-214-3p–Mediated High Expression of NCAPG Correlates With Poor Prognosis and Cell Proliferation in Non–Small Cell Lung Carcinoma

“…Tumor-infiltrating lymphocyte plays crucial roles in the prognosis of NSCLC ( Fan et al, 2021 ; Zeng et al, 2021 ). First, we used TIMER online analysis tool to examine the relationship between the immune infiltration and the somatic copy number alterations of NCAPG in LUAD.…”

Identification of Immune-Related Risk Characteristics and Prognostic Value of Immunophenotyping in TNBC

“…MMP9 is a matricellular protein associated with extracellular matrix (ECM) remodelling, promoting tumour progression, and modulating the activity of cell adhesion molecules and cytokines (Joseph et al, 2020;Mondal et al, 2020). MRPL15 is a member of mitochondrial ribosomal proteins whose abnormal expression is related to tumorigenesis in lung cancer, epithelial ovarian cancer and so on (Xu et al, 2021;Zeng et al, 2021). PDK4 is a member of PDK family located in the mitochondrial matrix of cells, inhibiting the entry of pyruvate into the TCA cycle by inhibiting pyruvate dehydrogenase activity.…”

Potential of Mitochondrial Ribosomal Genes as Cancer Biomarkers Demonstrated by Bioinformatics Results

“…Another study has demonstrated that high MRPL15 expression predicts a worse prognosis in non-small cell lung cancer; it revealed potential regulatory networks and demonstrated a negative correlation with immune infiltration (75). MRPL42 is highly expressed in early-stage lung adenocarcinoma (LUAD) tissues and cell lines and is significantly associated with prognosis.…”