# PRKAR1B as an oncogenic biomarker for diagnostic and prognostic stratification of tumor immunity, proliferation, and migration in head and neck squamous cell carcinoma

**Authors:** Peng Zhao, Kang Li, WuFeng Xiu, Zhaokun Liu, Yanxiao Huang, Youfang Jiang, Peng Zhang, Lixiang Peng

PMC · DOI: 10.3389/fimmu.2026.1770459 · Frontiers in Immunology · 2026-02-20

## TL;DR

PRKAR1B is a key biomarker in head and neck cancer, linked to poor outcomes, immune response, and drug sensitivity.

## Contribution

PRKAR1B is identified as a novel independent prognostic and predictive biomarker in HNSC.

## Key findings

- PRKAR1B is highly expressed in HNSC and is associated with poor prognosis.
- PRKAR1B correlates with immune cell infiltration and predicts response to CTLA-4 inhibitors.
- PRKAR1B knockdown reduces HNSC cell proliferation and migration in vitro.

## Abstract

Head and neck squamous cell carcinoma (HNSC) is one of the most prevalent malignancies worldwide. PRKAR1B, a regulatory component of protein kinase A (PKA), has been widely investigated for its potential involvement in tumorigenesis across different diseases. However, its specific role in HNSC remains elusive. In this study, significant differences in PRKAR1B expression were observed across various cancer types. PRKAR1B was highly expressed in HNSC and was strongly associated with poor prognosis in HNSC patients. Moreover, it was identified as an independent prognostic factor significantly associated with clinical parameters. Correlation analysis revealed that PRKAR1B expression was associated with genes such as C7orf50, EIF3B, TBRG4, DDX56, and BRAT1. Additionally, it was associated with TMB and was correlated with the infiltration of immune cells such as M1 macrophages, activated mast cells, and eosinophils. Notably, PRKAR1B was identified as a predictive marker for the efficacy of CTLA-4 inhibitors, with high PRKAR1B expression potentially conferring superior therapeutic responses. Drug sensitivity analysis further suggested that Lapatinib and Erlotinib may be beneficial in HNSC patients with high PRKAR1B expression. Meanwhile, in vitro experiments showed that PRKAR1B knockdown inhibited HNSC cell proliferation and migration. Lastly, PRKAR1B protein expression was upregulated in clinical HNSC samples. Overall, this study thoroughly examined PRKAR1B expression and its prognostic significance in HNSC, investigated related molecular pathways and immune cell interactions, and validated its role via in vitro experiments.

## Linked entities

- **Genes:** PRKAR1B (protein kinase cAMP-dependent type I regulatory subunit beta) [NCBI Gene 5575], CHLSN (cholesin) [NCBI Gene 84310], EIF3B (eukaryotic translation initiation factor 3 subunit B) [NCBI Gene 8662], TBRG4 (transforming growth factor beta regulator 4) [NCBI Gene 9238], DDX56 (DEAD-box helicase 56) [NCBI Gene 54606], BRAT1 (BRCA1 associated ATM activator 1) [NCBI Gene 221927]
- **Chemicals:** Lapatinib (PubChem CID 208908), Erlotinib (PubChem CID 176870)
- **Diseases:** head and neck squamous cell carcinoma (MONDO:0010150)

## Full-text entities

- **Genes:** CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, TNFRSF14 (TNF receptor superfamily member 14) [NCBI Gene 8764] {aka ATAR, CD270, HVEA, HVEM, LIGHTR, TR2}, BRAT1 (BRCA1 associated ATM activator 1) [NCBI Gene 221927] {aka BAAT1, C7orf27, NEDCAS, RMFSL}, CCL8 (C-C motif chemokine ligand 8) [NCBI Gene 6355] {aka HC14, MCP-2, MCP2, SCYA10, SCYA8}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, CD276 (CD276 molecule) [NCBI Gene 80381] {aka 4Ig-B7-H3, B7-H3, B7H3, B7RP-2}, PRKAR1B (protein kinase cAMP-dependent type I regulatory subunit beta) [NCBI Gene 5575] {aka MASNS, PRKAR1}, DDX56 (DEAD-box helicase 56) [NCBI Gene 54606] {aka DDX21, DDX26, NOH61}, EIF3B (eukaryotic translation initiation factor 3 subunit B) [NCBI Gene 8662] {aka EIF3-ETA, EIF3-P110, EIF3-P116, EIF3S9, PRT1}, NPY4R (neuropeptide Y receptor Y4) [NCBI Gene 5540] {aka NPY4-R, PP1, PPYR1, Y4}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, CHLSN (cholesin) [NCBI Gene 84310] {aka C7orf50, YCR016W}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, TBRG4 (transforming growth factor beta regulator 4) [NCBI Gene 9238] {aka CPR2, FASTKD4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}
- **Diseases:** STAD (MESH:D013274), organ dysfunction (MESH:D009102), autoimmune diseases (MESH:D001327), LUAD (MESH:D000077192), CHOL (MESH:D018281), tumorigenesis (MESH:D063646), HNSC (MESH:D000077195), Cervical squamous cell carcinoma (MESH:D002294), COAD (MESH:D003110), adrenal cortical disease (MESH:D018268), neurodegenerative diseases (MESH:D019636), inflammatory (MESH:D007249), melanoma (MESH:D008545), cancers (MESH:D009369), PRAD (MESH:D000230), head and neck tumors (MESH:D006258), READ (MESH:D012004), ACC (MESH:D004476), KICH (MESH:D007674), BRCA (MESH:D001943), candidiasis (MESH:D002177), ovarian cancer (MESH:D010051), liver cancer (MESH:D006528), ESCA (MESH:D004938), PCPG (MESH:D010673), GBM (MESH:D005909), KIRC (MESH:D002292), Staphylococcus aureus infection (MESH:D013203), metastasis (MESH:D009362), larynx (MESH:D007818), THCA (MESH:D013964), hematological diseases (MESH:D006402), breast, ovarian, and other cancers (MESH:D061325), UCEC (MESH:D016889), infection (MESH:D007239), N (MESH:C536108), toxicity (MESH:D064420)
- **Chemicals:** CCK-8 (MESH:D012844), EdU (MESH:C022811), SDS (MESH:D012967), Bleomycin (MESH:D001761), Vinorelbine (MESH:D000077235), Lapatinib (MESH:D000077341), cAMP (MESH:D000242), platinum (MESH:D010984), paraffin (MESH:D010232), proline (MESH:D011392), paclitaxel (MESH:D017239), hydrocortisone (MESH:D006854), Triton X-100 (MESH:D017830), streptomycin (MESH:D013307), polyamines (MESH:D011073), CO2 (MESH:D002245), Erlotinib (MESH:D000069347), paraformaldehyde (MESH:C003043), alcohol (MESH:D000438), PVDF (MESH:C024865), heparin (MESH:D006493), DAPI (MESH:C007293), cisplatin (MESH:D002945), AF488 (-), crystal violet (MESH:D005840), Doxorubicin (MESH:D004317), K (MESH:D011188), penicillin (MESH:D010406), capecitabine (MESH:D000069287), Etoposide (MESH:D005047), cetuximab (MESH:D000068818)
- **Species:** Human papillomavirus (species) [taxon 10566], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** CCK8 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2873), SCC25 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_1682), SCC9 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_7793)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12963008/full.md

## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963008/full.md

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Source: https://tomesphere.com/paper/PMC12963008