PMID- 35685693
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1178-7074 (Print)
IS  - 1178-7074 (Electronic)
IS  - 1178-7074 (Linking)
VI  - 15
DP  - 2022
TI  - Identification of a Necroptosis-Related Prognostic Index and Associated 
      Regulatory Axis in Kidney Renal Clear Cell Carcinoma.
PG  - 5407-5423
LID - 10.2147/IJGM.S367173 [doi]
AB  - BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is one of the most common 
      aggressive malignancies in the genitourinary system with the high degree of 
      immune infiltration. However, the role of necroptosis-related genes in the immune 
      infiltration of KIRC and the impact on overall survival have not been adequately 
      studied. METHODS: Differentially expressed necroptosis-related genes were 
      identified based on The Cancer Genome Atlas (TCGA). Then, we constructed a 
      necroptosis-related prognostic index (NRPI) through Lasso Cox regression 
      analysis. The KIRC patients were divided into NRPI-high and NRPI-low groups by 
      the median. Univariate and multivariate Cox regression analyses were used to 
      determine NRPI as an independent prognostic factor. The role of NRPI was assessed 
      through nomogram, GO/KEGG enrichment analyses, and immune cells infiltration. The 
      efficacy of immunotherapy in KIRC patients was evaluated by TIDE. The 
      immunohistochemistry was performed to verify the difference in protein expression 
      between tumor samples and normal tissues from our hospital. RESULTS: We found 
      that NRPI-high patients had higher mortality. The multivariate Cox regression 
      between the signature and multiple clinicopathological characteristics proved 
      that NRPI could effectively and independently predict the prognosis of KIRC. The 
      protein expression of three necroptosis-related genes constituting NRPI was 
      significantly different between tumor and normal tissues. NRPI was closely 
      related to immunologically relevant pathways and functions. The tumor 
      microenvironment and immune infiltrating cells showed clear distinctions in 
      NRPI-high and NRPI-low patients. The analysis of clinical treatments found that 
      NRPI-low patients responded better to immunotherapy, while NRPI-high patients 
      were more sensitive to targeted therapy. Furthermore, we identified a 
      lncRNAs/miRNA/mRNA regulatory axis for KIRC. CONCLUSION: In general, NRPI was a 
      promising biomarker in predicting the prognosis and responses to treatments in 
      KIRC.
CI  - (c) 2022 Luo and Zhang.
FAU - Luo, Yong
AU  - Luo Y
AUID- ORCID: 0000-0003-3614-4359
AD  - Department of Urology, the Second People's Hospital of Foshan, Affiliated Foshan 
      Hospital of Southern Medical University, Foshan, 528000, People's Republic of 
      China.
FAU - Zhang, Guian
AU  - Zhang G
AD  - School of Medicine, South China University of Technology, Guangzhou, 510006, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20220603
PL  - New Zealand
TA  - Int J Gen Med
JT  - International journal of general medicine
JID - 101515487
PMC - PMC9173730
OTO - NOTNLM
OT  - immune infiltration
OT  - immunotherapy
OT  - kidney renal clear cell carcinoma
OT  - necroptosis
OT  - prognostic index
COIS- The authors report no conflicts of interest in this work.
EDAT- 2022/06/11 06:00
MHDA- 2022/06/11 06:01
PMCR- 2022/06/03
CRDT- 2022/06/10 02:34
PHST- 2022/03/20 00:00 [received]
PHST- 2022/05/20 00:00 [accepted]
PHST- 2022/06/10 02:34 [entrez]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2022/06/11 06:01 [medline]
PHST- 2022/06/03 00:00 [pmc-release]
AID - 367173 [pii]
AID - 10.2147/IJGM.S367173 [doi]
PST - epublish
SO  - Int J Gen Med. 2022 Jun 3;15:5407-5423. doi: 10.2147/IJGM.S367173. eCollection 
      2022.