PMID- 38025816
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 2218-6751 (Print)
IS  - 2226-4477 (Electronic)
IS  - 2218-6751 (Linking)
VI  - 12
IP  - 10
DP  - 2023 Oct 31
TI  - SLC22A3 that encodes organic cation transporter-3 is associated with prognosis 
      and immunogenicity of human lung squamous cell carcinoma.
PG  - 1972-1986
LID - 10.21037/tlcr-23-334 [doi]
AB  - BACKGROUND: SLC22A3, the gene which encodes organic cation transporter (OCT)-3, 
      has been linked to the prognosis of several types of cancer. However, its role in 
      lung squamous cell carcinoma (LSCC) has not been addressed elsewhere. METHODS: We 
      analyzed gene expression, DNA methylation, and clinicopathological data from The 
      Cancer Genome Atlas - Lung Squamous Cell Carcinoma (TCGA-LUSC) (n=501), a 
      publicly available database exclusively consisting of LSCC patients. Using a 5 
      FPKM (fragments per kilobase of exon per million mapped fragments) cut-off, we 
      divided LSCC patients into two groups: patients with tumors possessing high and 
      low SLC22A3 expression (SLC22A3-high and SLC22A3-low, respectively). Prognostic 
      significance was determined through Cox analyses and Kaplan-Meier curves for 
      overall survival (OS) and disease-free survival (DFS). Differential methylation 
      position (DMP), differentially gene expression, and pathway analyses were 
      performed. Validation was carried out in GSE74777 (n=107), GSE37745 (n=66), 
      GSE162520 (n=45) and GSE161537 (n=17). RESULTS: SLC22A3-high LSCC patients had 
      lower OS and DFS rates than SLC22A3-low LSCC patients. The different expression 
      levels of SLC22A3 in LSCC were correlated with the methylation status of the 
      SLC22A3 gene. Pathway analysis indicated that SLC22A3 expression levels were 
      positively correlated with immune-related pathways such as inflammatory response 
      and abundance of infiltrating immune cells in the tumor microenvironment (TME). 
      Notably, in the SLC22A3-high group, many genes encoding immunological checkpoint 
      inhibitory molecules were upregulated. In addition, SLC22A3 expression positively 
      correlated with the Hot Oral Tumor (HOT) score, indicating high tumor 
      immunogenicity. CONCLUSIONS: These findings suggest that high expression of 
      SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors.
CI  - 2023 Translational Lung Cancer Research. All rights reserved.
FAU - Nguyen, Thuy-An
AU  - Nguyen TA
AD  - Department of Immunology, Faculty of Medicine, University of Yamanashi, 
      Yamanashi, Japan.
FAU - Le, Minh-Khang
AU  - Le MK
AD  - Department of Human Pathology, University of Yamanashi, Yamanashi, Japan.
FAU - Nguyen, Phuc-Tan
AU  - Nguyen PT
AD  - Department of Immunology, Faculty of Medicine, University of Yamanashi, 
      Yamanashi, Japan.
FAU - Tran, Nguyen Quoc Vuong
AU  - Tran NQV
AD  - Department of Immunology, Faculty of Medicine, University of Yamanashi, 
      Yamanashi, Japan.
FAU - Kondo, Tetsuo
AU  - Kondo T
AD  - Department of Human Pathology, University of Yamanashi, Yamanashi, Japan.
FAU - Nakao, Atsuhito
AU  - Nakao A
AD  - Department of Immunology, Faculty of Medicine, University of Yamanashi, 
      Yamanashi, Japan.
AD  - Yamanashi GLIA Center, University of Yamanashi, Yamanashi, Japan.
AD  - Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20231027
PL  - China
TA  - Transl Lung Cancer Res
JT  - Translational lung cancer research
JID - 101646875
PMC - PMC10654437
OTO - NOTNLM
OT  - Lung squamous cell carcinoma (LSCC)
OT  - SLC22A3
OT  - biomarker
OT  - inflammation
OT  - tumor microenvironment (TME)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-334/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2023/11/29 18:42
MHDA- 2023/11/29 18:43
PMCR- 2023/10/31
CRDT- 2023/11/29 16:37
PHST- 2023/05/24 00:00 [received]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2023/11/29 18:43 [medline]
PHST- 2023/11/29 18:42 [pubmed]
PHST- 2023/11/29 16:37 [entrez]
PHST- 2023/10/31 00:00 [pmc-release]
AID - tlcr-12-10-1972 [pii]
AID - 10.21037/tlcr-23-334 [doi]
PST - ppublish
SO  - Transl Lung Cancer Res. 2023 Oct 31;12(10):1972-1986. doi: 10.21037/tlcr-23-334. 
      Epub 2023 Oct 27.