# Differential SP4 expression and HSP60 abundance in buccal swabs from patients with schizophrenia

**Authors:** Christen M. Crosta, Brandon J. Vaglio, Joshua Stuckey, Atul K. Bhattiprolu, Johanne Solis, Jared Lamp, Andrew Umstead, Irving E. Vega, Steven M. Silverstein, Bonnie L. Firestein

PMC · DOI: 10.1126/sciadv.aeb0460 · Science Advances · 2026-03-04

## TL;DR

The paper explores using buccal cell biomarkers to identify and treat schizophrenia subgroups.

## Contribution

The study identifies Sp4 mRNA and HSP60 as potential biomarkers in buccal cells for schizophrenia subgroups.

## Key findings

- Sp4 mRNA levels are significantly different between schizophrenia patients and controls.
- HSP60 protein is elevated in schizophrenia samples.
- Elevated Sp4 and HSP60 correlate with symptom severity and memory issues in a subset of patients.

## Abstract

Schizophrenia (SCZ) is heterogenous and polygenic, making it difficult to diagnose and treat. This is expected as diagnostic criteria are solely based on behavioral markers. There is a critical need for easy-to-collect biomarkers that aid in treatment. To identify potential biomarkers, we recruited patients with SCZ and controls. Using buccal cell lysates, we performed real-time quantitative polymerase chain reaction and identified significant differences in Sp4 mRNA between patients and controls. Targeted mass spectrometry identified increased heat shock protein 60 (HSP60) in SCZ samples. To determine the utility of Sp4 mRNA and HSP60 protein as biomarkers, we evaluated their relationship with symptom severity and aberrant cognitive processes. Correlational analyses revealed that elevated Sp4 mRNA and HSP60 protein define a subgroup of patients with SCZ who demonstrate symptomology and poor memory. These data support buccal cell Sp4 mRNA and HSP60 protein as easy-to-collect, candidate SCZ biomarkers for a subset of patients.

Buccal cell biomarkers have the potential for diagnosis and treatment of schizophrenia.

## Linked entities

- **Genes:** SP4 (Sp4 transcription factor) [NCBI Gene 6671]
- **Proteins:** HSPD1 (heat shock protein family D (Hsp60) member 1)
- **Diseases:** schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], SP4 (Sp4 transcription factor) [NCBI Gene 6671] {aka HF1B, SPR-1}, NTF3 (neurotrophin 3) [NCBI Gene 4908] {aka HDNF, NGF-2, NGF2, NT-3, NT3}, GRIN2A (glutamate ionotropic receptor NMDA type subunit 2A) [NCBI Gene 2903] {aka EPND, FESD, GluN2A, LKS, NMDAR2A, NR2A}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, SP3 (Sp3 transcription factor) [NCBI Gene 6670] {aka SPR2}, NOS1AP (nitric oxide synthase 1 adaptor protein) [NCBI Gene 9722] {aka 6330408P19Rik, CAPON, NPHS22}, HSPD1 (heat shock protein family D (Hsp60) member 1) [NCBI Gene 3329] {aka CPN60, GROEL, HLD4, HSP-60, HSP60, HSP65}, RASD1 (ras related dexamethasone induced 1) [NCBI Gene 51655] {aka AGS1, DEXRAS1, MGC:26290}, HSP90B2P (heat shock protein 90 beta family member 2, pseudogene) [NCBI Gene 7190] {aka GRP94P1, GRP94b, HSP, HSPCP2, TRA1P1, TRAP1}
- **Diseases:** flat affect (MESH:D005413), abnormalities (MESH:D000014), symptoms (MESH:D012816), epilepsy (MESH:D004827), hallucinations (MESH:D006212), death (MESH:D003643), delusions (MESH:D063726), brain disorders (MESH:D001927), deficits in recognition discrimination (MESH:D010468), neurocognitive disorders (MESH:D019965), psychosis (MESH:D011618), depression (MESH:D003866), -5 (MESH:D008232), bipolar disorder (MESH:D001714), MS (MESH:D009103), hereditary spastic paraplegias (MESH:D015419), social disability (MESH:D003147), cognitive deficits (MESH:D003072), memory dysfunction (MESH:D008569), myasthenia gravis (MESH:D009157), inflammation (MESH:D007249), neurodegenerative disorders (MESH:D019636), visual integration deficits (MESH:D014786), Mitochondrial dysfunction (MESH:D028361), thought disturbance (MESH:D014832), Parkinson's disease (MESH:D010300), impaired delayed (MESH:D060825), Alzheimer's disease (MESH:D000544), Mental Disorders (MESH:D001523), paranoia (MESH:D010259), cancers (MESH:D009369), Huntington's disease (MESH:D006816), SCZ (MESH:D012559), anxiety (MESH:D001007), esophageal squamous cell carcinoma (MESH:D000077277), neurological diseases (MESH:D020271), autoimmune diseases (MESH:D001327), SCID-5 (MESH:D020914), learning and memory deficits (MESH:D007859), Negative and cognitive symptoms (MESH:D019954), oral cancers (MESH:D009062), seizures (MESH:D012640), tMS (MESH:C536030), SCID (MESH:D053632), oral squamous cell carcinoma (MESH:D000077195), disorganization (MESH:D012562)
- **Chemicals:** AM7020 (-), ethyl acetate (MESH:C007650), olanzapine (MESH:D000077152), AMBIC (MESH:C027043), quetiapine (MESH:D000069348), glucose (MESH:D005947), ice (MESH:D007053), haloperidol (MESH:D006220), methionine (MESH:D008715), CPT (MESH:C000708228), FA (MESH:C030544), acetonitrile (MESH:C032159), Peptides (MESH:D010455), Lithium (MESH:D008094), TRIzol (MESH:C411644), ACN (MESH:C084683), AX (MESH:D000658), risperidone (MESH:D018967)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12959401/full.md

## References

113 references — full list in the complete paper: https://tomesphere.com/paper/PMC12959401/full.md

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Source: https://tomesphere.com/paper/PMC12959401