# Unraveling the role of coagulation-related genes in esophageal squamous cell carcinoma: development of a prognostic model and exploration of potential clinical significance

**Authors:** Langlang Deng, Chen Fang, Weiran Zhang, Zheng Zhu, Yu Gu, Pinchao Gu, Xiaoyan Tan, Jiamin Yuan, Yu Feng, Haitao Ma

PMC · DOI: 10.3389/fonc.2025.1573279 · Frontiers in Oncology · 2025-10-07

## TL;DR

This study explores how coagulation-related genes affect esophageal cancer and develops a model to predict patient outcomes.

## Contribution

The study identifies seven coagulation-related genes and a prognostic model for ESCC, with RINT1 as a potential therapeutic target.

## Key findings

- A prognostic model based on seven coagulation-related genes effectively stratifies ESCC patients by risk.
- RINT1 shows differential expression in ESCC and may serve as a prognostic biomarker and therapeutic target.
- High- and low-risk groups differ in immune function, drug sensitivity, and disease pathways.

## Abstract

Esophageal squamous cell carcinoma (ESCC), the most common form of esophageal cancer, is associated with high incidence and mortality rates, representing a major public health challenge. Although previous research has suggested a link between coagulation dysfunction and cancer progression, the precise role of coagulation-related genes in ESCC remains poorly understood.

To investigate this, we integrated various multi-omics datasets, including mRNA expression data from TCGA and GEO, single-cell RNA sequencing data, as well as DNA mutation and methylation profiles. By applying machine learning algorithms, we identified coagulation-related genes in ESCC and developed a predictive model with clinical relevance. Further analyses were performed to assess the biological functions, prognostic significance, clinical implications, immune interactions, and drug sensitivity associated with these genes.

In this study, we identified seven coagulation feature genes—RAP1B, SRC, CFHR4, PLA2G4A, ORAI1, RINT1, and SPTB—in ESCC. A prognostic model based on these genes effectively stratified patients and demonstrated robust predictive value for clinical outcomes. Further analysis revealed distinct differences in immune function, drug sensitivity, and disease-related pathways between high- and low-risk groups. Among these genes, RINT1 emerged as a key factor, with pan-cancer analysis highlighting its potential relevance across multiple tumor types. We used immunohistochemistry, qRT-PCR, and Western blot to validate its differential expression in ESCC, highlighting its potential as a therapeutic target.

Our findings emphasize the significance of coagulation-related genes in ESCC progression and their involvement in critical biological and immune processes. The proposed prognostic model provides a valuable tool for risk assessment. Additionally, the identification of RINT1 provides new insights as a potential prognostic biomarker and candidate for future therapeutic investigation in ESCC patients.

## Linked entities

- **Genes:** RAP1B (RAP1B, member of RAS oncogene family) [NCBI Gene 5908], SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714], CFHR4 (complement factor H related 4) [NCBI Gene 10877], PLA2G4A (phospholipase A2 group IVA) [NCBI Gene 5321], ORAI1 (ORAI calcium release-activated calcium modulator 1) [NCBI Gene 84876], RINT1 (RAD50 interactor 1) [NCBI Gene 60561], SPTB (spectrin beta, erythrocytic) [NCBI Gene 6710]
- **Diseases:** esophageal squamous cell carcinoma (MONDO:0005580), ESCC (MONDO:0005580)

## Full-text entities

- **Genes:** RAP1B (RAP1B, member of RAS oncogene family) [NCBI Gene 5908] {aka K-REV, RAL1B, THC11}, RINT1 (RAD50 interactor 1) [NCBI Gene 60561] {aka ILFS3, RINT-1}, ORAI1 (ORAI calcium release-activated calcium modulator 1) [NCBI Gene 84876] {aka CRACM1, IMD9, ORAT1, TAM2, TMEM142A}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, CFHR4 (complement factor H related 4) [NCBI Gene 10877] {aka CFHL4, FHR-4, FHR4}, PLA2G4A (phospholipase A2 group IVA) [NCBI Gene 5321] {aka GURDP, PLA2G4, cPLA2, cPLA2-alpha}, SPTB (spectrin beta, erythrocytic) [NCBI Gene 6710] {aka EL3, HS2, HSPTB1, SPH2}
- **Diseases:** esophageal cancer (MESH:D004938), cancer (MESH:D009369), coagulation dysfunction (MESH:D001778), ESCC (MESH:D000077277)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12537425/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12537425/full.md

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Source: https://tomesphere.com/paper/PMC12537425