# Comprehensive pan-cancer analysis and experimental validation reveal FCHSD1 as a potential biomarker for diagnosis, immune infiltration, and prognosis

**Authors:** Ming Liu, Guixin Ding, Gonglin Tang, Shangjing Liu, Qiancheng Mao, Xidong Wang, Qingsong Zou, Jitao Wu

PMC · DOI: 10.3389/fonc.2025.1547067 · 2025-06-04

## TL;DR

This study shows that FCHSD1 is a promising biomarker for cancer diagnosis, immune infiltration, and prognosis across multiple cancer types.

## Contribution

The study is the first to comprehensively analyze FCHSD1's role in pan-cancer and its association with immune infiltration and prognosis.

## Key findings

- FCHSD1 expression is elevated in tumor tissues and linked to worse outcomes in cancers like CHOL and KIRC.
- High FCHSD1 expression correlates with increased immune cell infiltration in various cancers.
- FCHSD1 knockdown reduces cancer cell proliferation and migration in vitro.

## Abstract

FCHSD1 is a member of the F-BAR family containing one amino terminal F-BAR domain and two SH3 domains. At present, there are no relevant pan-cancer comprehensive studies on the predictive potential and immune infiltration of FCHSD1 for cancer.

FCHSD1 expression profiles were analyzed through the use of various tools, including TIMER, GEPIA, R packages, and the UALCAN database. The genetic alteration status of FCHSD1 in human pan-cancer was studied using the cBioPortal website. The effect of FCHSD1 on immune infiltration was examined using the TIMER and TISIDB databases. We confirmed the association between FCHSD1 expression and patient prognosis using survival analysis from GEPIA and R packages. The drug database was utilized to analyze the sensitivity of FCHSD1 to drugs. The FCHSD1 interactive genes were obtained through the STRING and GeneMANIA platforms, respectively, and analyzed by GO and KEGG. The expression and function of FCHSD1 in renal cancer cells and tissues have also been biologically validated in vitro.

FCHSD1 expression was found to be elevated in tumor tissues compared to adjacent tissues. The expression of FCHSD1 varied across different clinical stages, pathological stages, immune types, and molecular subtypes. Higher expression of FCHSD1 predicts worse outcomes for several cancer types, such as CHOL and KIRC. High FCHSD1 expression was positively correlated with immune cell infiltration in different cancer types. Additionally, the FCHSD1 co-expression gene network may be involved in endocytosis. In vitro experiments revealed that the expression of FCHSD1 in renal cancer cells and tissues was higher than that in normal cells and adjacent non-cancerous tissues. Functional assays revealed that FCHSD1 knockdown significantly suppressed proliferation and migration in ACHN and 769P cells.

FCHSD1 has the potential to serve as a prognostic and immunological marker for pan-cancer, and may also be a crucial target for future immunotherapy.

## Linked entities

- **Genes:** FCHSD1 (FCH and double SH3 domains 1) [NCBI Gene 89848]

## Full-text entities

- **Genes:** FCHSD1 (FCH and double SH3 domains 1) [NCBI Gene 89848] {aka NWK2}
- **Diseases:** cancer (MESH:D009369), pan (MESH:C537931), renal cancer (MESH:D007680)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** ACHN — Homo sapiens (Human), Papillary renal cell carcinoma, Cancer cell line (CVCL_1067), 769P — Homo sapiens (Human), Renal cell carcinoma, Cancer cell line (CVCL_1050)

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12173925/full.md

---
Source: https://tomesphere.com/paper/PMC12173925