Evidence map›Paper›PMID 42147807›Full record

ArticleHuman mutation2026

Secretory Lysosome-Related Gene Signature Defines the Immune Microenvironment and Identifies RGS2 as a Prometastatic Factor in Hepatocellular Carcinoma.

Zhipeng Ye, BuLang Tang, Yuanjian Zhang, Hanhan Chen, Jie Li, Zhitao Ye, Xuejian Liu, Jiaxi Li, Di Li

Abstract read
In one paragraph

Article in Human mutation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Zhipeng YeHepatology Unit, Departments of Infectious Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China, gzfezx.com.ORCID https://orcid.org/0009-0005-4152-055X
BuLang TangThe Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, gzhmc.edu.cn.ORCID https://orcid.org/0009-0004-0936-9477
Yuanjian ZhangHepatology Unit, Departments of Infectious Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China, gzfezx.com.ORCID https://orcid.org/0000-0002-0280-0269
Hanhan ChenGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China, gzhmc.edu.cn.ORCID https://orcid.org/0009-0003-2547-400X
Jie LiGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China, gzhmc.edu.cn.ORCID https://orcid.org/0009-0009-3684-5885
Zhitao YeGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China, gzhmc.edu.cn.ORCID https://orcid.org/0009-0004-7103-8214
Xuejian LiuDepartment of Radiology, Xinjiang 474 Hospital, Urumqi, China.ORCID https://orcid.org/0009-0001-8218-7141
Jiaxi LiDepartment of Clinical Laboratory, Xintang Hospital, Guangzhou, China.ORCID https://orcid.org/0009-0000-0291-0313
Di LiDepartment of Ultrasonography, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China, gzfezx.com.ORCID https://orcid.org/0009-0003-6808-3172

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Hepatocellular carcinoma (HCC) is a highly aggressive tumour with significant heterogeneity and a poor response to immunotherapy. Secretory lysosomes (SLs) control immunological responses and cellular homeostasis; however, the significance of secretory lysosome-related genes (SLRGs) in HCC prognosis and treatment is unclear. This work sought to create a predictive signature based on immune lysosome-related genes (immLysorgs) and to evaluate RGS2's functional role in HCC progression. Methods: We identified 13 immLysorgs in MSigDB and evaluated genomic and clinical data from the TCGA-LIHC and GSE76427 cohorts. Molecular subtypes were identified using nonnegative matrix factorization and consensus clustering. A predictive model (immLysoS) was built using LASSO and multivariate Cox regression with four genes: GZMH, KLRB1, RGS2, and SLC6A1. Model performance was validated across multiple cohorts. The involvement of RGS2 in HCC was examined using functional studies such as CCK-8, colony formation, migration assays, and a xenograft model. Results: Two subtypes (C1/C2) and two genotypes (A/B) were found, with the C2 and A groups exhibiting increased survival and immune infiltration. The immLysoS signature efficiently divided patients into risk categories, with low-risk individuals having much higher overall and progression-free survival. High immLysoS scores were associated with advanced disease, higher grade, and more TP53 and CTNNB1 mutations. Low-risk patients responded better to PD-L1 inhibitors with sorafenib. RGS2 knockdown drastically reduced HCC cell proliferation, migration, and tumor development both in vitro and in vivo. Discussion: The immLysoS signature is an effective tool for risk assessment and therapy advice in HCC, as it links SL-related genes to immunological characteristics and therapeutic response. RGS2 emerges as a possible oncogenic driver and therapeutic target, necessitating additional research into its processes in the HCC microenvironment.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsLysosomesRGS ProteinsTumor MicroenvironmentAnimalsBiomarkers, TumorCell Line, TumorCell MovementGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMicePrognosisBiomarkers, TumorRGS2 protein, humanRGS Proteinshepatocellular carcinomaimmunotherapyprognostic signatureRGS2risk stratificationsecretory lysosomestumor immune microenvironment

Identifiers

PMID42147807
PMCPMC13179717

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.