# Integrating Single-Cell and RNA Sequencing to Predict Glioma Prognosis Through Lactylation

**Authors:** Ruyi Shen, Yinan Chen, Yan Li, Zhijie Lin

PMC · DOI: 10.3390/ijms27041649 · 2026-02-08

## TL;DR

This study uses single-cell and RNA sequencing to identify a lactylation-related gene signature that predicts glioma prognosis and informs personalized treatment.

## Contribution

The study introduces a novel lactylation-related gene signature validated at single-cell resolution for glioma prognosis and treatment guidance.

## Key findings

- A lactylation-related risk model was developed and validated for predicting glioma patient survival.
- Risk groups showed distinct immune profiles and drug sensitivity patterns, aiding personalized treatment.
- The model integrates clinical variables and demonstrates potential for clinical application.

## Abstract

Gliomas are the most prevalent primary malignant neoplasms of the central nervous system, distinguished by their high recurrence rates and poor prognosis. Aerobic glycolysis in tumors generates excess lactate, which promotes lactylation, a post-translational modification (PTM). Although accumulating evidence implicates lactylation in glioma initiation and progression, previous lactylation-focused prognostic studies lacked single-cell resolution and broad validation, limiting their generalizability and clinical relevance. Single-cell and bulk RNA sequencing (RNA-seq) data were integrated to identify lactylation-enriched tumor cell populations and derive candidate genes. A risk model was developed using univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO), and its predictive performance was validated in independent cohorts from the China Glioma Genome Atlas (CGGA). To improve clinical applicability, a nomogram integrating the risk score incorporating key clinical variables was constructed and externally validated. The risk groups showed distinct immune microenvironment profiles and differential drug sensitivity patterns. In this study, we established and validated a lactylation-related gene signature, with the derived risk score serving as a reliable prognostic biomarker for glioma. Furthermore, the model not only predicts overall survival (OS) but also exhibits the potential to inform drug selection and stratify patients for more precise and personalized therapeutic interventions.

## Linked entities

- **Diseases:** glioma (MONDO:0021042)

## Full-text entities

- **Genes:** LDHB (lactate dehydrogenase B) [NCBI Gene 3945] {aka HEL-S-281, LDH-B, LDH-H, LDHBD, TRG-5}, TPX2 (TPX2 microtubule nucleation factor) [NCBI Gene 22974] {aka C20orf1, C20orf2, DIL-2, DIL2, FLS353, GD:C20orf1}, MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, PTTG1 (PTTG1 regulator of sister chromatid separation, securin) [NCBI Gene 9232] {aka EAP1, ECRAR, HPTTG, PTTG, TUTR1}, MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255], SDS (serine dehydratase) [NCBI Gene 10993] {aka SDH, hSDH}, AURKA (aurora kinase A) [NCBI Gene 6790] {aka AIK, ARK1, AURA, BTAK, PPP1R47, STK15}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, HMGN5 (high mobility group nucleosome binding domain 5) [NCBI Gene 79366] {aka NBP-45, NSBP1}, GPX7 (glutathione peroxidase 7) [NCBI Gene 2882] {aka CL683, GPX6, GPx-7, GSHPx-7, NPGPx}, NPY4R (neuropeptide Y receptor Y4) [NCBI Gene 5540] {aka NPY4-R, PP1, PPYR1, Y4}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, SMC4 (structural maintenance of chromosomes 4) [NCBI Gene 10051] {aka CAP-C, CAPC, SMC-4, SMC4L1}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, SHD (Src homology 2 domain containing transforming protein D) [NCBI Gene 56961], PDCD1LG2 (programmed cell death 1 ligand 2) [NCBI Gene 80380] {aka B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2}, C19orf53 (chromosome 19 open reading frame 53) [NCBI Gene 28974] {aka HSPC023, Hero11, L10K, LYDG10}, KIF4A (kinesin family member 4A) [NCBI Gene 24137] {aka KIF4, KIF4G1, MRX100, TMDI, XLID100}
- **Diseases:** papillary thyroid carcinoma (MESH:D000077273), gastric cancer (MESH:D013274), lung adenocarcinoma (MESH:D000077192), paragangliomas (MESH:D010235), Hypoxia (MESH:D000860), sarcoma (MESH:D012509), melanoma (MESH:D008545), Glioma (MESH:D005910), disease (MESH:D004194), injury to (MESH:D014947), MSI (MESH:D053842), Tumor (MESH:D009369), Dysfunction (MESH:D006331), breast cancer (MESH:D001943), cognitive deficits (MESH:D003072), GBM (MESH:D005909), NPC (MESH:D002292), pheochromocytomas (MESH:D010673), OS (MESH:D011475), colorectal cancer (MESH:D015179), gastrointestinal stromal tumors (MESH:D046152), hepatic metastasis (MESH:D009362), cytotoxic (MESH:D064420), Tumors of the Central Nervous System (MESH:D016543), Tumor Immune Dysfunction (MESH:D007154)
- **Chemicals:** Trametinib (MESH:C560077), TCA (MESH:D014233), Lactate (MESH:D019344), Olaparib (MESH:C531550), glucose (MESH:D005947), GSVA (-), Temozolomide (MESH:D000077204)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940179/full.md

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Source: https://tomesphere.com/paper/PMC12940179