# Proteomics analysis reveals elevated RAB21 in serum-derived extracellular vesicles from patients with follicular thyroid carcinoma

**Authors:** Kyojiro Kawakami, Naoki Edo, Koji Morita, Toshio Ishikawa, Hiroyuki Onose, Tatsuya Fukumori, Hiroki Tsumoto, Keitaro Umezawa, Masafumi Ito, Yuri Miura

PMC · DOI: 10.3892/ol.2025.15190 · Oncology Letters · 2025-07-16

## TL;DR

This study identifies RAB21 as a potential biomarker in blood vesicles for diagnosing follicular thyroid carcinoma and suggests it could be a treatment target.

## Contribution

The study identifies RAB21 as a novel serum EV biomarker for follicular thyroid carcinoma with potential diagnostic and therapeutic implications.

## Key findings

- RAB21 is significantly elevated in serum-derived extracellular vesicles from follicular thyroid carcinoma patients.
- RAB21 knockdown reduces cell migration and invasion in FTC cell lines, indicating its role in malignancy.
- RAB21 in serum EVs may serve as a candidate biomarker to distinguish FTC from follicular thyroid adenoma.

## Abstract

Follicular thyroid carcinoma (FTC) is a common thyroid malignancy that poses diagnostic challenges because of its cytological similarity to benign follicular thyroid adenoma (FTA). The present study aimed to identify characteristic protein signatures in serum-derived extracellular vesicles (EVs) of FTC and FTA for potential diagnostic and therapeutic applications. Serum EVs from patients with FTC and FTA were purified using the phosphatidylserine affinity method. Proteomics analysis via nano liquid chromatography-tandem mass spectrometry identified 18 significantly differentially expressed proteins between the two patient groups. RAB21, a small GTPase involved in cellular trafficking, was markedly elevated in serum EVs from patients with FTC. Furthermore, cell invasion and migration assays of a human FTC cell line revealed that RAB21 knockdown reduced cell migratory ability, suggesting its role in the malignant phenotype of FTC. The present findings indicated that RAB21 in serum EVs may be a candidate biomarker able to distinguish FTC from FTA, and that RAB21 could be a potential therapeutic target for FTC.

## Linked entities

- **Genes:** RAB21 (RAB21, member RAS oncogene family) [NCBI Gene 23011]
- **Proteins:** RAB21 (RAB21, member RAS oncogene family)
- **Diseases:** follicular thyroid carcinoma (MONDO:0005034), follicular thyroid adenoma (MONDO:0005032)

## Full-text entities

- **Genes:** KRT19 (keratin 19) [NCBI Gene 3880] {aka CK19, K19, K1CS}, ACVRL1 (activin A receptor like type 1) [NCBI Gene 94] {aka ACVRLK1, ALK-1, ALK1, HHT, HHT2, ORW2}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, TIMD4 (T cell immunoglobulin and mucin domain containing 4) [NCBI Gene 91937] {aka SMUCKLER, TIM4}, SAA1 (serum amyloid A1) [NCBI Gene 6288] {aka PIG4, SAA, TP53I4}, TFF3 (trefoil factor 3) [NCBI Gene 7033] {aka ITF, P1B, TFI}, RAB21 (RAB21, member RAS oncogene family) [NCBI Gene 100683312], NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, FLOT2 (flotillin 2) [NCBI Gene 2319] {aka ECS-1, ECS1, ESA, ESA1, M17S1}, TSHR (thyroid stimulating hormone receptor) [NCBI Gene 7253] {aka CHNG1, LGR3, hTSHR-I}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, DICER1 (dicer 1, ribonuclease III) [NCBI Gene 23405] {aka DCR1, Dicer, Dicer1e, GLOW, HERNA, K12H4.8-LIKE}, PLVAP (plasmalemma vesicle associated protein) [NCBI Gene 83483] {aka DIAR10, FELS, PV-1, PV1, gp68}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, KRT13 (keratin 13) [NCBI Gene 3860] {aka CK13, K13, WSN2}, RASA1 (RAS p21 protein activator 1) [NCBI Gene 5921] {aka CM-AVM, CMAVM, CMAVM1, GAP, PKWS, RASA}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, RAB21 (RAB21, member RAS oncogene family) [NCBI Gene 23011], PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, PDCD6IP (programmed cell death 6 interacting protein) [NCBI Gene 10015] {aka AIP1, ALIX, DRIP4, HP95, MCPH29}, FHL1 (four and a half LIM domains 1) [NCBI Gene 2273] {aka FCMSU, FHL-1, FHL1A, FHL1B, FLH1A, KYOT}, TALDO1 (transaldolase 1) [NCBI Gene 6888] {aka TAL, TAL-H, TALDOR, TALH}, CPQ (carboxypeptidase Q) [NCBI Gene 10404] {aka LDP, PGCP}
- **Diseases:** FT-UMP (MESH:C537245), benign tumors (MESH:D009369), FTA (MESH:D000236), FTC (MESH:D018263), head and neck squamous cell carcinoma (MESH:D000077195), glioma (MESH:D005910), metastases (MESH:D009362), PDAC (MESH:D021441), follicular lesions (MESH:D005497), BRCA (MESH:D001943), AN (MESH:D011125), primary thyroid carcinoma (MESH:D013964), PTC (MESH:D000077273)
- **Chemicals:** CO2 (MESH:D002245), streptomycin (MESH:D013307), polyacrylamide (MESH:C016679), water (MESH:D014867), phosphatidylserine (MESH:D010718), PS (MESH:D010758), CaCl2 (MESH:D002122), lipids (MESH:D008055), SDS (MESH:D012967), 2-mercaptoethanol (MESH:D008623), CPC100 (-), crystal violet (MESH:D005840), HCl (MESH:D006851), formalin (MESH:D005557), methionine (MESH:D008715), penicillin (MESH:D010406), Peptides (MESH:D010455), TEAB (MESH:C041737), cysteine (MESH:D003545), iodoacetamide (MESH:D007460), glucose (MESH:D005947), acetonitrile (MESH:C032159), methanol (MESH:D000432), EDTA (MESH:D004492), paraffin (MESH:D010232), FA (MESH:C030544), Lipofectamine (MESH:C086724), dithiothreitol (MESH:D004229), PVDF (MESH:C024865), bromophenol blue (MESH:D001978), glycerol (MESH:D005990)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** FTC-133 — Homo sapiens (Human), Thyroid gland papillary carcinoma, Cancer cell line (CVCL_6308)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12308455/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12308455/full.md

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Source: https://tomesphere.com/paper/PMC12308455