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
. 2025 Feb 25;14(1):14-22.
doi: 10.62347/XVFP6530. eCollection 2025.

The prognostic significance of FMR1 expression and its immunomodulatory implications in esophageal carcinoma

Qingqin Tang  1 , Yanqiu Zhang  2 , Yuting Liang  1 , Jun Qiu  1 , Sheng Zhang  1 , Jieyu Jin  1 , Jun Cao  1 , Longwei Qiao  3 , Bin Feng  1
Affiliations

The prognostic significance of FMR1 expression and its immunomodulatory implications in esophageal carcinoma

Qingqin Tang et al. Am J Clin Exp Immunol. .

Abstract

Background: Esophageal carcinoma (ESCA) is deemed a highly lethal malignancy with a grim prognosis and stands as the fourth leading cause of cancer-related mortality. Recent research has revealed the potential crucial role of fragile X mental retardation 1 (FMR1) protein in tumor development and progression. However, the correlation between FMR1 and immune regulation in ESCA remains unclear. In this study, we aimed to assess the clinicopathological and prognostic significance of FMR1 expression, and its relationship with immune cell infiltration, immune biomarkers and the pathway involved in ESCA.

Methods: The Cancer Genome Atlas (TCGA) pan-cancer data and the Gene Expression Omnibus (GEO) database were used to analyze the expression of FMR1. The correlation between FMR1 and cancer stage, time-dependent survival curve and receiver operating characteristic (ROC) curve were performed using R package. Immune cell infiltration was assessed using the samples found in TCGA. Functional enrichment analyses were performed to investigate the potential signaling pathway and biological functions.

Results: FMR1 was upregulated in 7 tumors and downregulated in 4 tumors. Overexpression of FMR1 considerably associated with cancer stage and poor prognosis in ESCA. The ROC area was 0.745 and 0.830 for 3-year and 5-year respectively. FMR1 exhibited a positive correlation with common lymphoid progenitor and T cell CD4+ Th2, and a negative correlation with B cell memory, B cell plasma, endothelial cell, monocyte, neutrophil, T cell CD4+ Th1, and T cell CD4+ effector memory in ESCA. The enrichment analysis revealed FMR1 was primarily associated with cell development and predominantly enriched in immune-related pathways.

Conclusion: FMR1 may act as a prognostic biomarker for ESCA and participate in immune regulation in ESCA.

Keywords: Esophageal carcinoma; immune cell infiltration; immune regulation; prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors state that they conducted the research without any commercial or financial relationships that could be considered a potential conflict of interest.

Figures

Figure 1
Figure 1
Pan-cancer analysis of FMR1 expression in primary tumor and normal tissues from TCGA data (A) or TCGA and GTEx data (B). FMR1 expression in ESCA and normal tissues from TCGA data (C) or TCGA and GTEx data (D). (E) FMR1 expression in paired cancer tissues of ESCA from TCGA data. (F) Promoter methylation level of FMR1 in ESCA and normal samples from TCGA data. (G) ROC curve of FMR1 for ESCA diagnosis.
Figure 2
Figure 2
FMR1 expression in normal and cancer tissues of ESCA with different tumor stage (A) or different pathologic stage (B) or different histologic grade (C).
Figure 3
Figure 3
Association between FMR1 expression and tumor prognosis, including (A) overall survival, (B) progress free survival, (C) disease specific survival of ESCA patients in TCGA. (D) The area of ROC for 3-year and 5-year in ESCA patients.
Figure 4
Figure 4
The top genes of most positively associated with FMR1 in different cancers.
Figure 5
Figure 5
Function and pathway enrichment analysis of FMR1 in ESCA. A, B. Connection analysis between FMR1 and other genes in ESCA. C. Significant Gene Ontology terms of the top 449 genes most positively associated with FMR1, including biological processes (BP), molecular function (MF), and cell component (CC). D. Significant KEGG pathways of the top 449 genes most positively associated with FMR1. E. Significant GSEA results of the top 449 genes most positively associated with FMR1.
See this image and copyright information in PMC

References

    1. Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, Laversanne M, Ferlay J, Arnold M. The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and Projections to 2040: new estimates from GLOBOCAN 2020. Gastroenterology. 2022;163:649–658. e2. - PubMed
    1. Waters JK, Reznik SI. Update on management of squamous cell esophageal cancer. Curr Oncol Rep. 2022;24:375–385. - PubMed
    1. Lam AK. Introduction: esophageal squamous cell carcinoma-current status and future advances. Methods Mol Biol. 2020;2129:1–6. - PubMed
    1. Niu C, Liu Y, Wang J, Liu Y, Zhang S, Zhang Y, Zhang L, Zhao D, Liu F, Chao L, Wang X, Zhang C, Song G, Zhang Z, Li Y, Yan Z, Wen Y, Ge Y, Zang Z, Feng W, Zhang H, Tao L, Nakyeyune R, Shen Y, Shao Y, Guo X, Miles T, Yang A, Liu F, Wang G. Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study. BMC Cancer. 2021;21:1034. - PMC - PubMed
    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;71:209–249. - PubMed

LinkOut - more resources