# A Multi-Gene Signature Associated with 1-Year Survival in Patients with Stage I Liver Cancer: Integration of Preclinical and TCGA Data

**Authors:** Ritam Adhikari, Bhaskar V. S. Kallakury, Chiranjeev Dash, Rabindra Roy

PMC · DOI: 10.3390/cimb48020136 · 2026-01-27

## TL;DR

A new five-gene panel was developed to predict 1-year survival in early-stage liver cancer patients using rat and human data.

## Contribution

A novel five-gene biomarker panel for 1-year survival prediction in Stage I liver cancer patients was developed and validated.

## Key findings

- A rat model and TCGA data were combined to identify a five-gene panel linked to 1-year survival in Stage I liver cancer.
- The panel was validated using REMARK guidelines and shows potential for further external validation.
- No existing Stage-I-specific prognostic tools currently exist, highlighting the novelty of this panel.

## Abstract

Approximately 50% of individuals diagnosed with Stage I liver cancer live beyond four years; however, a small subset of Stage I patients die within the first year. A prognostic biomarker panel that can identify high-risk Stage I patients may be extremely valuable. In this study, we used the Long–Evans Cinnamon (LEC) rat model of Wilson’s Disease and hepatocellular carcinoma (HCC), along with data from The Cancer Genome Atlas (TCGA) human database, to create a novel biomarker panel. We generated and analyzed a rat microarray gene expression profile by comparing liver tumor tissues with adjacent normal tissues from the same animals, covering approximately 30,000 genes. The microarray results were translated into a five-gene panel associated with 1-year survival in Stage I liver cancer patients based on TCGA data, in combination with machine learning and bioinformatics approaches. The panel was internally validated following the “REporting recommendations for Tumor MARKer prognostic studies (REMARK)” guidelines. With no existing Stage-I-specific prognostic tools, a biomarker panel associated with 1-year survival in patients with Stage I liver cancer is a potential candidate for rigorous external validation.

## Linked entities

- **Diseases:** Wilson’s Disease (MONDO:0010200), hepatocellular carcinoma (MONDO:0007256), liver cancer (MONDO:0002691)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** GK (glycerol kinase) [NCBI Gene 2710] {aka GK1, GKD}, CD24 (CD24 molecule) [NCBI Gene 100133941] {aka CD24A}, USP54 (ubiquitin specific peptidase 54) [NCBI Gene 159195] {aka C10orf29, bA137L10.3, bA137L10.4}, Usp54 (ubiquitin specific peptidase 54) [NCBI Gene 408223], PAQR9 (progestin and adipoQ receptor family member 9) [NCBI Gene 344838] {aka BLNC1}, ITGB4 (integrin subunit beta 4) [NCBI Gene 3691] {aka CD104, GP150, JEB5A, JEB5B}, Mgp (matrix Gla protein) [NCBI Gene 25333] {aka Mglap}, Paqr9 (progestin and adipoQ receptor family member 9) [NCBI Gene 315904], Atp7b (ATPase copper transporting beta) [NCBI Gene 24218] {aka Hts, PINA, Wd}, ANXA2 (annexin A2) [NCBI Gene 302] {aka ANX2, ANX2L4, CAL1H, HEL-S-270, LIP2, LPC2}, AOC1 (amine oxidase copper containing 1) [NCBI Gene 26] {aka ABP, ABP1, DAO, DAO1, KAO, KDAO}, FXYD3 (FXYD domain containing ion transport regulator 3) [NCBI Gene 5349] {aka MAT8, PLML}
- **Diseases:** hepatitis virus infections (MESH:D006525), LEC (MESH:C536380), death (MESH:D003643), esophageal carcinoma (MESH:D004938), HCC (MESH:D006528), chronic (MESH:D002908), liver tumor (MESH:D008113), copper (MESH:C535468), breast cancer (MESH:D001943), HPA (MESH:C483996), liver injury (MESH:D017093), hepatitis (MESH:D056486), Cancer (MESH:D009369), lung cancer (MESH:D008175), iron overload (MESH:D019190), fibrosis (MESH:D005355), injury to (MESH:D014947), disease (MESH:D004194), MASLD (MESH:D008107), chronic hepatitis (MESH:D006521), hepatic inflammation (MESH:D007249), genetic disorders (MESH:D030342), WD (MESH:D006527), LUAD (MESH:D000077192), I (MESH:D006969)
- **Chemicals:** H&amp;E (MESH:D006371), LEC (-), hematoxylin (MESH:D006416), alcohol (MESH:D000438), H (MESH:D006859), eosin (MESH:D004801), paraffin (MESH:D010232), copper (MESH:D003300), E (MESH:D004540)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** LEC — Mus musculus (Mouse), Transformed cell line (CVCL_0P24)

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939873/full.md

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Source: https://tomesphere.com/paper/PMC12939873