AccScience Publishing / GPD / Volume 2 / Issue 1 / DOI: 10.36922/gpd.363
Cite this article
Journal Browser
Volume | Year
News and Announcements
View All

Underexpression of SCN7A is associated with poor prognosis in lung adenocarcinoma

Hehui Lv1,2† Hongyuan Song1,2† Zhouping Qin1,2† Rongchun Xing1,2 Yulian Chen1,2*
Show Less
1 First Hospital of Yichang, Hubei, China
2 People’s Hospital of China Three Gorges University, Hubei, China
Submitted: 8 February 2023 | Accepted: 16 March 2023 | Published: 27 March 2023
© 2023 by the Author(s). Licensee AccScience Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Lung cancer is one of the most common malignancies and the leading cause of cancer-related deaths worldwide. Elucidating the mechanism behind the development of lung cancer at a molecular level could reveal new biomarkers and clinical therapeutic targets. A growing body of evidence has shown an association between ion channel-related genes and the progression of various diseases, including cancer. However, the association is not well-understood. In this study, we identified ion channel-related genes differentially expressed between cancer and normal lung tissue cells. Data were extracted from GSE31552, GSE33532, and GSE103512 lung adenocarcinoma (LUAD) datasets, and the prognostic value of the differentially expressed genes between LUAD and normal lung tissue was evaluated using data in The Cancer Genome Atlas. Only sodium voltage-gated channel alpha subunit 7 (SCN7A) was found to be significantly correlated to prognosis. The expression of SCN7A in LUAD was assessed further by immunological analysis. We also constructed a competing endogenous RNA network of SCN7A. Further analyses revealed that the underexpression of SCN7A predicted a poor prognosis in LUAD, with a strong correlation between SCN7A expression and immune cell infiltration as well as immune checkpoint expression. We found that SCN7A is potentially regulated via the OTUD6B-AS1-miR-21-5p-SCN7A axis in LUAD cells and proved that SCN7A inhibits the proliferation and migration of lung cancer cells in vitro. Taken together, SCN7A, as an independent prognostic factor, is a promising diagnostic biomarker for LUAD, and the OTUD6B-AS1-miR-21-5p-SCN7A axis is a potential regulatory network of SCN7A expression.

Lung adenocarcinoma
Gene Expression Omnibus
The Cancer Genome Atlas
Immune infiltration
Competing endogenous RNA

Thai AA, Solomon BJ, Sequist LV, et al., 2021, Lung cancer. Lancet, 398(10299): 535–554.


Siegel RL, Miller KD, Jemal A, 2019, Cancer statistics, 2019. CA Cancer J Clin, 69(1): 7–34.


Knight SB, Crosbie PA, Balata H, et al., 2017, Progress and prospects of early detection in lung cancer. Open Biol, 7(9): 170070.


Nooreldeen R, Bach H, 2021, Current and future development in lung cancer diagnosis. Int J Mol Sci, 22(16): 8661.


Bulk E, Todesca LM, Schwab A, 2021, Ion channels in lung cancer. Rev Physiol Biochem Pharmacol, 181: 57–79.


Farfariello V, Prevarskaya N, Gkika D, 2021, Ion channel profiling in prostate cancer: Toward cell population-specific screening. Rev Physiol Biochem Pharmacol, 181: 39–56.


Fu S, Hirte H, Welch S, et al., 2017, First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors. Invest New Drugs, 35(3): 324–333.


Fairhurst C, Watt I, Martin F, et al., 2015, Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: A population-based study. Sci Rep, 5: 16758.


Martin F, Ufodiama C, Watt I, et al., 2015, Therapeutic value of voltage-gated sodium channel inhibitors in breast, colorectal, and prostate cancer: A systematic review. Front Pharmacol, 6: 273. 


Lin J, Marquardt G, Mullapudi N, et al., 2014, Lung cancer transcriptomes refined with laser capture microdissection. Am J Pathol, 184(11): 2868–2884. 


Meister M, Belousov A, Xu EC, et al., 2014, Intra-tumor heterogeneity of gene expression profiles in early stage non-small cell lung cancer. J Bioinform Res Stud, 1(1): 21.


Brouwer-Visser J, Cheng WY, Bauer-Mehren A, et al., 2018, Regulatory T-cell genes drive altered immune microenvironment in adult solid cancers and allow for immune contextual patient subtyping. Cancer Epidemiol Biomarkers Prev, 27(1): 103–112.


Barrett T, Wilhite SE, Ledoux P, et al., 2013, NCBI GEO: Archive for functional genomics data sets--update. Nucleic Acids Res, 41(Database issue): D991–D995.


Zhou Y, Zhou B, Pache L, et al., 2019, Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun, 10(1): 1523.


Uhlen M, Fagerberg L, Hallström BM, et al., 2015, Proteomics. Tissue-based map of the human proteome. Science, 347(6220): 1260419. 


Gao J, Aksoy BA, Dogrusoz U, et al., 2013, Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal, 6(269): pl1. 


Cerami E, Gao J, Dogrusoz U, et al., 2012, The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov, 2(5): 401–404.


Li T, Fu J, Zeng Z, et al., 2020, TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res, 48(W1): W509–W514.


Cho S, Jang I, Jun Y, et al., 2013, MiRGator v3.0: A microRNA portal for deep sequencing, expression profiling and mRNA targeting. Nucleic Acids Res, 41(Database issue): D252–D257.


Li JH, Liu S, Zhou H, et al., 2014, starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res, 42(Database issue): D92–D97.


Camerino DC, Tricarico D, Desaphy JF, 2007, Ion channel pharmacology. Neurotherapeutics, 4(2): 15.


Petho Z, Najder K, Bulk E, et al., 2019, Mechanosensitive ion channels push cancer progression. Cell Calcium, 80: 79–90.


Anderson KJ, Cormier RT, Scott PM, 2019, Role of ion channels in gastrointestinal cancer. World J Gastroenterol, 25(38): 5732–5772.


Li W, Zhou K, Li M, et al., 2022, Identification of SCN7A as the key gene associated with tumor mutation burden in gastric cancer. BMC Gastroenterol, 22(1): 45.


Yan Y, He W, Chen Y, et al., 2021, Comprehensive analysis to identify the encoded gens of sodium channels as a prognostic biomarker in hepatocellular carcinoma. Front Genet, 12: 802067. 


Dolivo D, Rodrigues A, Sun L, et al., 2021, The Na(x) (SCN7A) channel: An atypical regulator of tissue homeostasis and disease. Cell Mol Life Sci, 78(14): 5469–5488.


Feske S, Wulff H, Skolnik EY, 2015, Ion channels in innate and adaptive immunity. Annu Rev Immunol, 33: 291–353.


Bujak JK, Kosmala D, Szopa IM, et al., 2019, Inflammation, cancer and immunity-implication of TRPV1 channel. Front Oncol, 9: 1087.


Zhao J, Xie P, Galiano RD, et al., 2019, Imiquimod-induced skin inflammation is relieved by knockdown of sodium channel Nax. Exp Dermatol, 28(5): 576–584.


Zhao J, Jia S, Xie P, et al., 2020, Knockdown of sodium channel Na(x) reduces dermatitis symptoms in rabbit skin. Lab Invest, 100(5): 751–761.


Ghafouri-Fard S, Shoorei H, Anamag FT, et al., 2020, The role of non-coding rnas in controlling cell cycle related proteins in cancer cells. Front Oncol, 10: 608975. 


Razavi ZS, Tajiknia V, Majidi S, et al., 2021, Gynecologic cancers and non-coding RNAs: Epigenetic regulators with emerging roles. Crit Rev Oncol Hematol, 157: 103192.


Fabrizio FP, Sparaneo A, Muscarella LA, 2020, NRF2 regulation by noncoding RNAs in cancers: The present knowledge and the way forward. Cancers (Basel), 12(12): 3621. 


Gao S, Ding B, Lou W, 2020, microRNA-dependent modulation of genes contributes to ESR1’s effect on ERalpha positive breast cancer. Front Oncol, 10: 753.


Cai Y, Li Y, Shi C, et al., 2021, LncRNA OTUD6B-AS1 inhibits many cellular processes in colorectal cancer by sponging miR-21-5p and regulating PNRC2. Hum Exp Toxicol, 40(9): 1463–1473.


Wang W, Cheng X, Zhu J, 2021, Long non-coding RNA OTUD6B-AS1 overexpression inhibits the proliferation, invasion and migration of colorectal cancer cells via downregulation of microRNA-3171. Oncol Lett, 21(3): 193.


Wang Z, Xia F, Feng T, et al., 2020, OTUD6B-AS1 inhibits viability, migration, and invasion of thyroid carcinoma by targeting miR-183-5p and miR-21. Front Endocrinol (Lausanne), 11: 136.


Tang J, Li X, Cheng T, et al., 2021, miR-21-5p/SMAD7 axis promotes the progress of lung cancer. Thorac Cancer, 12(17): 2307–2313.


Zhou X, Liu H, Pang Y, et al., 2022, UTMD-mediated delivery of miR-21-5p inhibitor suppresses the development of lung cancer. Tissue Cell, 74: 101719.


Bao L, Zhang Y, Wang J, et al., 2016, Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer. Cell Biol Toxicol, 32(5): 419–435.

Conflict of interest
The authors declare that they have no competing interests.
Back to top
Gene & Protein in Disease, Electronic ISSN: 2811-003X Print ISSN: TBA, Published by AccScience Publishing