PMID- 36003381
OWN - NLM
STAT- MEDLINE
DCOM- 20220826
LR  - 20220901
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - A novel tumor mutational burden-based risk model predicts prognosis and 
      correlates with immune infiltration in ovarian cancer.
PG  - 943389
LID - 10.3389/fimmu.2022.943389 [doi]
LID - 943389
AB  - Tumor mutational burden (TMB) has been reported to determine the response to 
      immunotherapy, thus affecting the patient's prognosis in many cancers. However, 
      it is unclear whether TMB or TMB-related signature could be used as prognostic 
      indicators for ovarian cancer (OC), as its potential association with immune 
      infiltration remains poorly understood. Therefore, this study aimed to develop a 
      novel TMB-related risk model (TMBrisk) to predict the prognosis of OC patients on 
      the basis of exploring TMB-related genes, and to explore the potential 
      association between TMB/TMBrisk and immune infiltration. The mutational 
      landscape, TMB scores, and correlations between TMB and clinical characteristics 
      and immune infiltration were investigated in The Cancer Genome Atlas (TCGA)-OV 
      cohort. Differentially expressed gene (DEG) analyses and weighted gene 
      co-expression network analysis (WGCNA) were performed to derive TMB-related 
      genes. TMBrisk was constructed by Cox regression and further validated in Gene 
      Expression Omnibus (GEO) datasets. The mRNA and protein expression levels and 
      biological functions of TMBrisk hub genes were verified through Gene Expression 
      Profiling Interactive Analysis (GEPIA), GSCA Lite, the Human Protein Atlas (HPA) 
      database, and RT-qPCR. TMBrisk-related biological phenotypes were analyzed in 
      function enrichment and tumor immune infiltration signature. Potential 
      therapeutic regimens were inferred utilizing the Genomics of Drug Sensitivity in 
      Cancer (GDSC) database and connectivity map (CMap). According to our results, 
      higher TMB was associated with better survival and higher CD8+ T cell, regulatory 
      T cell, and NK cell infiltration. TMBrisk was developed based on CBWD1, ST7L, 
      RFX5-AS1, C3orf38, LRFN1, LEMD1, and HMGB1. High TMBrisk was identified as a poor 
      factor for prognosis in TCGA and GEO datasets; the high-TMBrisk group comprised 
      more higher-grade (G2 and G3) and advanced clinical stage (stage III/IV) tumors. 
      Meanwhile, higher TMBrisk was associated with an immunosuppressive phenotype, 
      with less infiltration of a majority of immunocytes and less expression of 
      several genes of the human leukocyte antigen (HLA) family. Moreover, a nomogram 
      containing TMBrisk showed a strong predictive ability demonstrated by 
      time-dependent ROC analysis. Overall, this novel TMB-related risk model (TMBrisk) 
      could predict prognosis, evaluate immune infiltration, and discover new 
      therapeutic regimens in OC, which is very promising in clinical promotion.
CI  - Copyright (c) 2022 Wang, Liu, Yang, Wang, Zhang, Peng, Wang and Hong.
FAU - Wang, Haoyu
AU  - Wang H
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Liu, Jingchun
AU  - Liu J
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Yang, Jiang
AU  - Yang J
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Wang, Zhi
AU  - Wang Z
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Zhang, Zihui
AU  - Zhang Z
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Peng, Jiaxin
AU  - Peng J
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Hong, Li
AU  - Hong L
AD  - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, 
      Wuhan, China.
LA  - eng
SI  - figshare/10.6084/m9.figshare.19729651.v2
PT  - Journal Article
DEP - 20220808
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ST7L protein, human)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - *Biomarkers, Tumor/genetics/metabolism
MH  - CD8-Positive T-Lymphocytes
MH  - Carcinoma, Ovarian Epithelial/genetics/pathology
MH  - Female
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating
MH  - *Ovarian Neoplasms/genetics/pathology
MH  - Prognosis
MH  - Tumor Suppressor Proteins
PMC - PMC9393426
OTO - NOTNLM
OT  - gene signature
OT  - immune infiltration
OT  - immunotherapy
OT  - ovarian cancer
OT  - risk model
OT  - tumor mutational burden (TMB)
OT  - weighted gene correlation network analysis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/26 06:00
MHDA- 2022/08/27 06:00
PMCR- 2022/01/01
CRDT- 2022/08/25 02:20
PHST- 2022/05/13 00:00 [received]
PHST- 2022/07/18 00:00 [accepted]
PHST- 2022/08/25 02:20 [entrez]
PHST- 2022/08/26 06:00 [pubmed]
PHST- 2022/08/27 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.943389 [doi]
PST - epublish
SO  - Front Immunol. 2022 Aug 8;13:943389. doi: 10.3389/fimmu.2022.943389. eCollection 
      2022.