Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 18;16(2):1605-1619.
doi: 10.18632/aging.205446. Epub 2024 Jan 18.

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis

Fang-Ming Wang  1 , Li-Qiang Xu  2 , Zhong-Chao Zhang  3 , Qiang Guo  2 , Zhi-Peng Du  3 , Yue Lei  4 , Xu Han  3 , Chuang-Yan Wu  1 , Feng Zhao  1 , Jiu-Ling Chen  1
Affiliations

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis

Fang-Ming Wang et al. Aging (Albany NY). .

Abstract

Background: Overexpression of solute carrier family 7 member 8 (SLC7A8) has been shown to relate to the survival time and tumor progression in cancer patients. However, the role of SLC7A8 in lung adenocarcinoma (LUAD) is still obscure.

Method: The relationships between SLC7A8 expression in LUAD tissues and clinical values as well as immune infiltration were explored through bioinformatics. The functions and pathways of SLC7A8 in LUAD were investigated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, Western blotting, and other methods.

Results: We found that the expression of SLC7A8 was decreased significantly in LUAD tissues compared with normal tissues, which was related to the dismal survival time and disease progression. Moreover, it carried diagnostic value in LUAD and was a risk factor for dismal prognosis. Receiver operating characteristic curve analysis indicated that the expression level of SLC7A8 carried significant diagnostic value in LUAD. Overexpression of SLC7A8 inhibited the proliferation, invasion, and migration of LUAD cells, likely through a mechanism involving the cell cycle. SLC7A8 expression in LUAD was significantly correlated with the infiltration of immune cells, especially B cells, interstitial dendritic cells, mast cells, CD56 bright cells, natural killer cells, plasmacytoid dendritic cells, T follicular helper cells, T helper 2 and 17 cells, and immune factors.

Conclusion: The downregulation of SLC7A8 was related to a dismal prognosis and immune cell infiltration in LUAD. Increasing the expression of SLC7A8 inhibited the growth and migration of LUAD cells, thereby improving the prognosis of patients.

Keywords: SLC7A8; TCGA; immune infiltration; lung adenocarcinoma; prognosis.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study.

Figures

Figure 1
Figure 1
The expression level of SLC7A8 in LUAD based on TPM data from TCGA and Xena. (A) TPM data of unpaired tissues from TCGA. (B) TPM data of unpaired tissues from Xena. (C) TPM data of paired tissues from TCGA. Abbreviations: LUAD: lung adenocarcinoma; TCGA: The Cancer Genome Atlas; TPM: transcripts per million.
Figure 2
Figure 2
ROC curve analysis indicating the diagnostic value of SLC7A8 in LUAD. (A) TPM data from TCGA. (B) TPM data from Xena. Abbreviation: ROC: receiver operating characteristic.
Figure 3
Figure 3
Expression level of SLC7A8 is associated with the prognosis of LUAD patients. SLC7A8 expression is associated with (A) OS in LUAD patients, (B) DSS in LUAD patients, (C) PFI in LUAD patients. Abbreviations: OS: overall survival; DSS: disease-specific survival; PFI: progression-free interval.
Figure 4
Figure 4
The nomogram shows the correlation between low expression of SLC7A8 and poor prognosis of LUAD.
Figure 5
Figure 5
Overexpression of SLC7A8 suppresses the migration and invasion of LUAD. (A) The expression level of SLC7A8 in BEAS-2B, A549, and H1299 cells. (B) The protein expression levels were determined by Western blotting. (C) The migration and invasion were assessed using Transwell assays. (D) The migration ability was determined using wound healing assays as well.
Figure 6
Figure 6
(A) Cell proliferation in the SLC7A8-overexpressing group was demonstrated using the CCK-8 assays. (B) Cell proliferation in the SLC7A8-overexpressing group was demonstrated using and colony forming assays. Abbreviation: CCK-8: Cell Counting Kit-8.
Figure 7
Figure 7
PPI network of genes strongly co-expressed with SLC7A8. Abbreviation: PPI: protein–protein interaction.
Figure 8
Figure 8
Mechanisms associated with SLC7A8. (A–F) Mechanisms associated with SLC7A8 were explored using GSEA. (G) The expression levels of the cell cycle proteins CDK1 and CCNB1. Abbreviations: GSEA: Gene Set Enrichment Analysis; CDK1: cyclin-dependent kinase-1; CCNB1: cyclin B1.
Figure 9
Figure 9
SLC7A8 expression is correlated with immune infiltrated cells. (A) B cells. (B) iDC. (C) Mast cells. (D) NK CD56 bright cells. (E) NK cells. (F) pDC. (G) TFH. (H) Th2 cells. (I) Th17 cells.
Figure 10
Figure 10
SLC7A8 expression is correlated with immune factors. (A) CD5. (B) CD34. (C) CD36. (D) CD37. (E) CD79B. (F) CDA. (G) CDC7. (H) CCL4. (I) CCL28.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71:209–49. 10.3322/caac.21660 - DOI - PubMed
    1. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014; 14:535–46. 10.1038/nrc3775 - DOI - PMC - PubMed
    1. Zhang L, Zhang Y, Wang C, Yang Y, Ni Y, Wang Z, Song T, Yao M, Liu Z, Chao N, Yang Y, Shao J, Li Z, et al.. Integrated single-cell RNA sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer. Signal Transduct Target Ther. 2022; 7:9. 10.1038/s41392-021-00824-9 - DOI - PMC - PubMed
    1. He L, Chen J, Xu F, Li J, Li J. Prognostic Implication of a Metabolism-Associated Gene Signature in Lung Adenocarcinoma. Mol Ther Oncolytics. 2020; 19:265–77. 10.1016/j.omto.2020.09.011 - DOI - PMC - PubMed
    1. Breitenecker K, Homolya M, Luca AC, Lang V, Trenk C, Petroczi G, Mohrherr J, Horvath J, Moritsch S, Haas L, Kurnaeva M, Eferl R, Stoiber D, et al.. Down-regulation of A20 promotes immune escape of lung adenocarcinomas. Sci Transl Med. 2021; 13:eabc3911. 10.1126/scitranslmed.abc3911 - DOI - PMC - PubMed

Publication types

Substances