Skip to main content

Advertisement

Log in

Identification of Key lncRNAs Associated with Immune Infiltration and Prognosis in Gastric Cancer

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Long non-coding RNAs (lncRNAs), as promising novel biomarkers for cancer treatment and prognosis, can function as tumor suppressors and oncogenes in the occurrence and development of many types of cancer, including gastric cancer (GC). However, little is known about the complex regulatory system of lncRNAs in GC. In this study, we systematically analyzed lncRNA and miRNA transcriptomic profiles of GC based on bioinformatics methods and experimental validation. An lncRNA-miRNA interaction network related to GC was constructed, and the nine crucial lncRNAs were identified. These 9 lncRNAs were found to be associated with the prognosis of GC patients by Cox proportional hazards regression analysis. Among them, the expression of lncRNA SNHG14 can affect the survival of GC patients as a potential prognostic marker. Moreover, it was shown that SNHG14 was involved in immune-related pathways and significantly correlated with immune cell infiltration in GC. Meanwhile, we found that SNHG14 affected immune function in many cancers, such as breast cancer and esophageal carcinoma. Such information revealed that SNHG14 may serve as a potential target for cancer immunotherapy. As well, our study could provide practical and theoretical guiding significance for clinical application of non-coding RNAs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

All data analyzed during the present study are publicly available at TCGA data portal (https://portal.gdc.cancer.gov/).

References

  • Ahadi A (2021) A systematic review of microRNAs as potential biomarkers for diagnosis and prognosis of gastric cancer, Immunogenetics

  • Ashwini J et al (2012) Debora, miRcode: a map of putative microRNA target sites in the long non-coding transcriptome, Bioinformatics

  • Damian S, Gable AL, Nastou KC et al (2020) The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res D1

  • Di W, Weinan X, Xin L et al (2019) Long noncoding RNA SNHG14 facilitates colorectal cancer metastasis through targeting EZH2-regulated EPHA7. Cell Death Dis 10:514

    Article  PubMed  PubMed Central  Google Scholar 

  • Far BF, Vakili K, Fathi M et al (2023) The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: a review. Life Sci 316:121340

    Article  Google Scholar 

  • Gao Y, Wang J, Ren J et al (2020) Long noncoding RNAs in gastric cancer: from molecular dissection to clinical application. World J Gastroenterol 26:3401–3412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Z, Han H, Zhao Y et al (2021) A tumor microenvironment-related mRNA-ncRNA signature for prediction early relapse and chemotherapeutic sensitivity in early-stage lung adenocarcinoma. J Cancer Res Clin Oncol 147:3195–3209

    Article  CAS  PubMed  Google Scholar 

  • Goodall G, Wickramasinghe V (2021) RNA in cancer, Nature reviews. Cancer 21:22–36

    CAS  PubMed  Google Scholar 

  • He C, Liu Y, Li J et al (2022) LncRNA RPSAP52 promotes cell proliferation and inhibits cell apoptosis via modulating miR-665/STAT3 in gastric cancer. Bioengineered 13:8699–8711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hosseini SA, Haddadi MH, Fathizadeh H et al (2023) Long non-coding RNAs and gastric cancer: an update of potential biomarkers and therapeutic applications. Biomed Pharmacotherapy = Biomedecine Pharmacotherapie 163:114407

    Article  CAS  PubMed  Google Scholar 

  • Huang HY, Lin Y, Li J et al (2019) miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database. Nuclc Acids Res

  • Huang D, Zhang K, Zheng W et al (2021) Long noncoding RNA SGO1-AS1 inactivates TGFβ signaling by facilitating TGFB1/2 mRNA decay and inhibits gastric carcinoma metastasis. J Experimental Clin cancer Research: CR 40:342

    Article  PubMed Central  Google Scholar 

  • Ishaque N, Abba M, Hauser C et al (2018) Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer. Nat Commun 9:4782

    Article  PubMed  PubMed Central  Google Scholar 

  • Jager KJ, van Dijk PC, Zoccali C et al (2008) The analysis of survival data: the Kaplan-Meier method. Kidney Int 74:560–565

    Article  PubMed  Google Scholar 

  • Jia Y, Yan Q, Zheng Y et al (2022) Long non-coding RNA NEAT1 mediated RPRD1B stability facilitates fatty acid metabolism and lymph node metastasis via c-Jun/c-Fos/SREBP1 axis in gastric cancer. J Experimental Clin cancer Research: CR 41:287

    Article  CAS  PubMed Central  Google Scholar 

  • Kanda M, Tanaka H, Shimizu D et al (2018) SYT7 acts as a driver of hepatic metastasis formation of gastric cancer cells. Oncogene 37:5355–5366

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann SHE (2019) Immunology’s coming of Age. Front Immunol 10:684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696:291–303

    Article  CAS  PubMed  Google Scholar 

  • Li H, Long C, Xiang J et al (2020a) Dppa2/4 as a trigger of signaling pathways to promote zygote genome activation by binding to CG-rich region. Brief Bioinform

  • Li Y, Jiang T, Zhou W et al (2020b) Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers. Nat Commun 11:1000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Zhang C, Shi Y et al (2021a) Identification of KEY lncRNAs and mRNAs Associated with oral squamous cell carcinoma progression. Curr Bioinform 16:207–215

    Article  CAS  Google Scholar 

  • Li C, Tang Z, Zhang W et al (2021b) GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA. Nucleic Acids Res 49:W242–W246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Du Y, Wang Y (2021c) The value of LncRNA SNHG5 as a marker for the diagnosis and prognosis of gastric cancer. Am J Translational Res 13:5420–5427

    CAS  Google Scholar 

  • Li D, Xu M, Wang Z et al (2022) The EMT-induced lncRNA NR2F1-AS1 positively modulates NR2F1 expression and drives gastric cancer via miR-29a-3p/VAMP7 axis. Cell Death Dis 13:84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang P, Yang W, Chen X et al (2020) Machine learning of single-cell transcriptome highly identifies mRNA signature by comparing F-Score selection with DGE analysis. Mol Therapy - Nucleic Acids 20:155–163

    Article  CAS  Google Scholar 

  • Liang P, Zheng L, Long C et al (2021) HelPredictor models single-cell transcriptome to predict human embryo lineage allocation, 22

  • Liao Z, Zhang H, Su C et al (2021) Long noncoding RNA SNHG14 promotes hepatocellular carcinoma progression by regulating miR-876-5p/SSR2 axis. J Experimental Clin cancer Research: CR 40:36

    Article  CAS  PubMed Central  Google Scholar 

  • Lin Z, Song J, Gao Y et al (2022) Hypoxia-induced HIF-1α/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer. Redox Biol 52:102312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu G, Li H, Ji W et al (2021) Construction of a ceRNA network in glioma and analysis of its clinical significance. BMC Genomics 22:722

    Article  PubMed  PubMed Central  Google Scholar 

  • Love MI, Huber W, Anders S (2014) Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma Z, Shuai Y, Gao X et al (2020) BTEB2-Activated lncRNA TSPEAR-AS2 drives GC progression through suppressing GJA1 expression and upregulating CLDN4 expression, Molecular therapy. Nucleic Acids 22:1129–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piao H, Liu Y, Kang Y et al (2021) Hypoxia associated lncRNA HYPAL promotes proliferation of gastric cancer as ceRNA by sponging mir-431-5p to upregulate CDK14, gastric cancer: official. J Int Gastric Cancer Association Japanese Gastric Cancer Association

  • Rugolo F, Bazan N, Calandria J et al (2021) The expression of ELOVL4, repressed by MYCN, defines neuroblastoma patients with good outcome, Oncogene

  • Slack FJ, Chinnaiyan AM (2019) The role of non-coding RNAs in Oncology. Cell 179:1033–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang W, Wan S, Yang Z et al (2018) Tumor origin detection with tissue-specific miRNA and DNA methylation markers. Bioinf (Oxford England) 34:398–406

    CAS  Google Scholar 

  • Tang Q, Shi X, Xu Y et al (2023) Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning, Biochemical genetics

  • Tian Y, Li L, Lin G et al (2021) lncRNA SNHG14 promotes oncogenesis and immune evasion in diffuse large-B-cell lymphoma by sequestering miR-152-3p. Leuk Lymphoma 62:1574–1584

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Yu F, Chen X et al (2020) The underlying mechanisms of noncoding RNAs in the Chemoresistance of Hepatocellular Carcinoma, Molecular therapy. Nucleic Acids 21:13–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Liang P, Zheng L et al (2021) eHSCPr discriminating the cell identity involved in endothelial to hematopoietic transition, Bioinformatics

  • Wang C, Zhao D, Shu X et al (2022) Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis. J Cancer Res Clin Oncol 148:121–135

    Article  CAS  PubMed  Google Scholar 

  • Wei Z, Chen L, Meng L et al (2020) LncRNA HOTAIR promotes the growth and metastasis of gastric cancer by sponging mir-1277-5p and upregulating COL5A1. Gastric Cancer 23

  • Wu Q, Zhang B, Wang Z et al (2019) Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gastric cancer. Pathol Res Pract 215:1038–1048

    Article  CAS  PubMed  Google Scholar 

  • Xiao T, Jie Z (2019) MiR-21 promotes the Invasion and Metastasis of Gastric Cancer cells by activating epithelial-mesenchymal transition, European surgical research. Europaische Chirurgische Forschung Recherches Chirurgicales Europeennes 60:208–218

    Article  CAS  PubMed  Google Scholar 

  • Xie S, Chang Y, Jin H et al (2020) Non-coding RNAs in gastric cancer. Cancer Lett

  • Xu MD, Wang Y, Weng W et al (2017) A positive Feedback Loop of lncRNA-PVT1 and FOXM1 facilitates gastric Cancer Growth and Invasion. Clin cancer Research: Official J Am Association Cancer Res 23:2071–2080

    Article  CAS  Google Scholar 

  • Yang Q, Wu J, Zhao J et al (2020) The expression profiles of lncRNAs and their Regulatory Network during Smek1/2 knockout mouse neural stem cells differentiation. Curr Bioinform 15:77–88

    Article  CAS  Google Scholar 

  • Yang Z, Li Q, Zheng X et al (2021) Long noncoding RNA small nucleolar host gene: a potential therapeutic target in Urological Cancers. Front Oncol 11:638721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang H, Hu Y, Weng M et al (2022) Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. J Adv Res 37:91–106

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Duan W, Mo Z et al (2020) Upregulation of SNHG14 suppresses cell proliferation and metastasis of colorectal cancer by targeting miR-92b-3p. J Cell Biochem 121:1998–2008

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Dong X, Guo X et al (2023) LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer. Mol Cancer 22:41

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao L, Guo H, Zhou B et al (2016) Long non-coding RNA SNHG5 suppresses gastric cancer progression by trapping MTA2 in the cytosol. Oncogene 35:5770–5780

    Article  CAS  PubMed  Google Scholar 

  • Zhao L, Han T, Li Y et al (2017) The lncRNA SNHG5/miR-32 axis regulates gastric cancer cell proliferation and migration by targeting KLF4, FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 31:893–903

  • Zhao L, Liu Y, Zhang J et al (2019) LncRNA SNHG14/miR-5590-3p/ZEB1 positive feedback loop promoted diffuse large B cell lymphoma progression and immune evasion through regulating PD-1/PD-L1 checkpoint. Cell Death Dis 10:731

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao C, Xu H, Liu C (2023) Identification of Novel Prognostic Long Non-coding RNAs in Lung Adenocarcinoma Using WGCNA Analysis, Biochemical genetics

  • Zhuo W, Liu Y, Li S et al (2019) Long noncoding RNA GMAN, Up-regulated in gastric Cancer tissues, is Associated with metastasis in patients and promotes translation of ephrin A1 by competitively binding GMAN-AS. Gastroenterology 156:676–691e611

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by Natural Science Foundation of Inner Mongolia (No. 2022QN06007); the National Natural Science Foundation of China (No. 81960449, 62171241 and 62061034); the Science Research Foundation of Inner Mongolia People’s Hospital (No. 2021YN18); the Science and Technology Planning Project for Health of Inner Mongolia (No. 202202024); and the Talent Training Plan for the Key Laboratory of Inner Mongolia Science and Technology Department.

Author information

Authors and Affiliations

Authors

Contributions

W.J. and J.J. contributed to the design, bioinformatics analysis, drafting and writing of the manuscript. Y.S. and H.L. participated in data analysis. J.L. devoted the work of negotiation and revising the manuscript. H.Z. and Z.W. performed samples collection and biological experiment. L.Y. and Y.Z. provided full guidance of the study. All authors have read and approved the final manuscript for submission.

Corresponding authors

Correspondence to Yongchun Zuo or Lan Yu.

Ethics declarations

Ethics Approval and Consent to Participate

The tissue samples used in this study have been approved by the Medical Ethics Committee of Inner Mongolia People’s Hospital. All of the patients signed the informed consent for beforehand.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jin, W., Jia, J., Si, Y. et al. Identification of Key lncRNAs Associated with Immune Infiltration and Prognosis in Gastric Cancer. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10801-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10528-024-10801-w

Keywords

Navigation