# MIR4435-2HG: a key player in the novel lncRNA prognostic signatures causes early metastasis after tumor resection and poor prognosis for esophageal squamous cell carcinoma

## TL;DR

This study identifies MIR4435-2HG, a long non-coding RNA, as a biomarker linked to early metastasis and poor outcomes in esophageal cancer.

## Contribution

The study introduces MIR4435-2HG as a novel lncRNA biomarker for esophageal squamous cell carcinoma prognosis and metastasis.

## Key findings

- MIR4435-2HG is significantly upregulated in tumor tissues with poor prognosis.
- High MIR4435-2HG expression correlates with advanced tumor stage and shorter survival.
- MIR4435-2HG promotes tumor growth and metastasis via the PI3K-Akt pathway.

## Abstract

Esophageal squamous cell carcinoma (ESCC) is a major histopathological type of esophageal cancer. Tumor metastasis is a critical factor that dramatically worsens the prognosis, leading to a decline in survival rates. Understanding the molecular mechanisms underlying metastasis and identifying reliable biomarkers to predict metastasis susceptibility are essential for improving patient outcomes. This study aims to explore the role of lncRNA MIR4435-2HG in ESCC metastasis susceptibility and its potential as a prognostic biomarker.

We conducted a genome-wide analysis of gene expression in ESCC tissues from four patients with similar clinical characteristics but divergent prognoses to identify differentially expressed lncRNAs and mRNAs. We focused on the lncRNA MIR4435-2HG, examining its expression levels in correlation with clinical outcomes and its role in the PI3K-Akt pathway through in vitro experiments and bioinformatics analysis.

Differential expression analysis identified 2000 prognosis-related lncRNAs, with MIR4435-2HG showing significant upregulation in tumor tissues of patients with poor prognosis. High expression levels of MIR4435-2HG were associated with advanced tumor stage and short-term survival. The key lncRNA-miRNA-mRNA axes in the prognostic sub-network offer insights into the interactions most relevant to cancer prognosis. The results of in vitro experiments and enrichment analysis suggested that MIR4435-2HG promotes tumor proliferation and metastasis by activating the PI3K-Akt pathway.

MIR4435-2HG may represent a potential biomarker associated with metastasis and poor prognosis. Its possible involvement in the PI3K-Akt pathway warrants further validation and investigation in larger clinical cohorts.

The online version contains supplementary material available at 10.1186/s12885-025-15299-y.