Discovery and preliminary validation of five early gastric cancer biomarkers, including TAGLN2 and CTSD, based on serum proteomics

doi:10.19401/j.cnki.1007-3639.2025.06.003

Abstract

Abstract:

Background and purpose: Gastric cancer, as one of the most common malignant tumors, requires early diagnosis and treatment to improve patient prognosis. This study, based on serum quantitative proteomics research of early-stage gastric cancer patients and non-gastric cancer patients, aims to identify potential diagnostic biomarkers for early gastric cancer. Methods: Serum samples from primary gastric cancer patients and healthy control individuals were collected from Lanzhou University Second Hospital between June and December 2023, following inclusion and exclusion criteria. A protein spectral library was established using Data-Dependent Acquisition (DDA) mode, and each sample was analyzed using Data-Independent Acquisition (DIA) mode. The STRING database was used to analyze protein-protein interactions of upregulated proteins in gastric cancer serum. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used to analyze the pathways and functional annotations of the corresponding genes. Gene expression levels in gastric cancer and non-gastric cancer tissues were analyzed using GEPIA 2, and overall survival of each gene in gastric cancer was analyzed using Kaplan-Meier Plotter. Differential gene expression in clinical gastric cancer and adjacent tissues was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) This study was approved by the Ethics Committee of Lanzhou University Second Hospital (Ethical No.: 2023A-459) and was exempt from the informed consent. Results: Finally, serum samples from 30 primary gastric cancer patients, 29 healthy control individuals, along with the para-cancerous tissues from 8 patients were collected. A total of 666 intersecting proteins were identified through serum quantitative proteomics. Among them, 16 proteins showed upregulated expression and 22 proteins showed downregulated expression in the gastric cancer group (P<0.05, |FC|≥1.5). STRING database analysis showed that 10 upregulated proteins were involved in interaction networks. KEGG and GO analysis indicated that these genes were closely related to the biological processes of cancer occurrence and development. GEPIA 2 and Kaplan-Meier Plotter analysis showed that 6 genes, B2M, TAGLN2, CTSD, HSP90AB1, SH3BGRL3, and CFL1, which were highly expressed in the gastric cancer group (P<0.05) and associated with poor prognosis. Clinical verification by qRT-PCR confirmed that TAGLN2, CTSD, SH3BGRL3, CFL1 and HSP90AB1 were highly expressed in gastric cancer tissues (P<0.05). Conclusion: TAGLN2, CTSD, SH3BGRL3, CFL1, and HSP90AB1 have the potential to serve as clinical early gastric cancer diagnostic serum biomarkers, which may facilitate early diagnosis and treatment of gastric cancer.

Key words: Proteomics, Gastric cancer, Biomarkers, Early diagnosis

CLC Number:

R735.2

DU Kewei, ZHANG Shangdi, HU Wenfei, GAO Shan, GAN Jianxin, YOU Chongge. Discovery and preliminary validation of five early gastric cancer biomarkers, including TAGLN2 and CTSD, based on serum proteomics[J]. China Oncology, 2025, 35(6): 543-554.

Figures/Tables 7

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Genes	Sequence
B2M(human)	Forward: 5’-TGTCTCGCTCCGTGGCCTTAG-3’
	Reverse: 5’-CTCTGCTGGATGACGTGAGTAAACC-3’
TAGLN2(human)	Forward: 5’-ATGGCACGGTGCTATGTGAG-3’
	Reverse: 5’-CCCACCCAGATTCATCAGCG-3’
CTSD(human)	Forward: 5’-ACGGGCTCCTCCAACCTGTG-3’
	Reverse: 5’-TGGACTTGTCGCTGTTGTACTTGTG-3’
HSP90AB1(human)	Forward: 5’-GAAACCGCCCTGCTATCTTCTGG-3’
	Reverse: 5’-CCTCTGCTGCCACTTCATCTTCATC-3’
SH3BGRL3(human)	Forward: 5’-CTCCCGCGAAATCAAGTCCC-3’
	Reverse: 5’-CCCGTTGACAATCTGGGGTG-3’
CFL1(human)	Forward: 5’-TACGCCACCTTTGTCAAGATG-3’
	Reverse: 5’-CCTTGGAGCTGGCATAAATCAT-3’

Genes	Protein IDs	GCNM average	NC average	P value^*	GCNM-vs-NC Regulation
HSP90AB1	P08238	0.232	0.080	0.002	Up
SH3BGRL3	Q9H299	0.105	0.044	0.004	Up
KIAA1958	Q8N8K9	0.814	0.244	0.005	Up
FLNA	P21333	0.153	0.048	0.006	Up
CTSD	P07339	0.125	0.081	0.011	Up
B2M	P61769	0.682	0.355	0.013	Up
CFL1	P23528	0.354	0.186	0.015	Up
MPO	P05164	0.133	0.079	0.017	Up
IGFBP2	P18065	0.162	0.091	0.018	Up
HPSE	Q9Y251	0.058	0.019	0.020	Up
IGLV1-51	P01701	15.209	6.972	0.021	Up
ANTXR1	Q9H6X2	0.060	0.021	0.023	Up
TAGLN2	P37802	0.324	0.116	0.024	Up
IGHV3-21	A0A0B4J1V1	0.092	0.052	0.025	Up
RAP1B	P61224	0.141	0.049	0.032	Up
GSTO1	P78417	0.117	0.055	0.040	Up
IGKC	P01834	46.167	83.347	0.001	Down
PTPRJ	Q12913	0.101	0.183	0.003	Down
CHST9	Q7L1S5	0.317	1.457	0.004	Down
IGKV2D-30	A0A075B6S6	0.082	0.264	0.005	Down
HNRNPA1	P09651	0.105	0.185	0.006	Down
IGLV4-69	A0A075B6H9	0.300	3.710	0.012	Down
MDH2	P40926	0.044	0.101	0.014	Down
CORO1A	P31146	0.053	0.198	0.014	Down
ABCC5	O15440	0.836	2.019	0.019	Down
CENPU	Q71F23	0.071	0.129	0.020	Down
NME2	P22392	0.059	0.095	0.022	Down
RBBP9	O75884	0.227	0.472	0.027	Down
PARVG	Q9HBI0	0.192	0.381	0.028	Down
PZP	P20742	0.844	1.740	0.028	Down
B4GAT1	O43505	0.011	0.029	0.035	Down
AFDN	P55196	0.062	0.098	0.035	Down
HBA2	P69905	26.864	45.432	0.036	Down
GOT1	P17174	0.028	0.053	0.038	Down
IGHV1-45	A0A0A0MS14	0.466	0.713	0.038	Down
PRDX2	P32119	0.122	0.196	0.042	Down
UBR4	Q5T4S7	0.055	0.091	0.045	Down
TUBA4A	P68366	0.015	0.038	0.046	Down