Identification of SRSF2 as a potential immunodiagnostic biomarker for osteosarcoma: A study based on focused protein microarray

doi:10.5306/wjco.v17.i5.119275

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World Journal of Clinical Oncology

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2218-4333

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Clin Oncol. May 24, 2026; 17(5): 119275
Published online May 24, 2026. doi: 10.5306/wjco.v17.i5.119275

Identification of SRSF2 as a potential immunodiagnostic biomarker for osteosarcoma: A study based on focused protein microarray

Yan Ma, Lei Wan, Yong-Yong Zhang, Ya-Ge Luo, Ning Yang, Fei-Fei Pu, Malik Ihsan Ullah Khan, Man Liu, Jin-Shan Liu, Ji-Tian Li

Yan Ma, Yong-Yong Zhang, Ya-Ge Luo, Ning Yang, Man Liu, Ji-Tian Li, Henan Provincial Health Commission Key Laboratory of Bone Metabolism and Analysis, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China

Lei Wan, Department of Osteology, The Second Affiliated Hospital of Luohe Medical College, Luohe 462300, Henan Province, China

Fei-Fei Pu, Department of Orthopedics, Wuhan No. 1 Hospital, Wuhan 430022, Hubei Province, China

Malik Ihsan Ullah Khan, Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore 54792, Punjab, Pakistan

Malik Ihsan Ullah Khan, School of Food Science and Engineering, Hainan University, Haikou 570228, Hainan Province, China

Jin-Shan Liu, Department of Orthopedic, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao 028000, Inner Mongolia Autonomous Region, China

Ji-Tian Li, Graduate School, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China

Ji-Tian Li, Clinical Medical Center of Tissue Engineering and Regeneration, The Third Affiliated Hospital of Henan Medical University, Henan Medical University, Xinxiang 453000, Henan Province, China

Co-first authors: Yan Ma and Lei Wan.

Co-corresponding authors: Jin-Shan Liu and Ji-Tian Li.

Author contributions: Ma Y and Wan L wrote the manuscript and they contributed equally to this manuscript and are co-first authors; Ma Y and Zhang YY performed the experiments; Wan L and Luo YG collected and interpreted the data; Yang N and Pu FF responsible for review and revision; Khan MIU, Liu M, Liu JS, and Li JT designed and coordinated the study; Liu JS and Li JT contributed equally to this manuscript and are co-corresponding authors. All authors have read and approved the final manuscript.

Supported by China Association of Chinese Medicine Young Talent Support Program, No. 2021-QNCRC2-A06; the Traditional Chinese Medicine Research in Henan Province, No. 2023ZY2136; Research Project of China Information Association of Traditional Chinese Medicine, No. CACMS-KY-2023030; and Henan Province Collaborative Research Project on Traditional Chinese Medicine Science and Technology Special Program, No. 2025 LHZX5043.

Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province). The patients/participants provided their written informed consent to participate in this study.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Corresponding author: Ji-Tian Li, MD, PhD, Professor, Henan Provincial Health Commission Key Laboratory of Bone Metabolism and Analysis, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Henan University of Chinese Medicine, No. 100 Yongping Road, Zhengzhou 450046, Henan Province, China. jitianlee@hotmail.com

Received: January 26, 2026
Revised: February 11, 2026
Accepted: March 26, 2026
Published online: May 24, 2026
Processing time: 116 Days and 21.9 Hours

Abstract

BACKGROUND

Osteosarcoma (OS) is a primary solid tumor of bone. Due to the insidious onset and malignancy of OS, it is necessary to diagnose OS earlier.

AIM

To search for an optimal diagnostic biomarker, such as autoantibody against tumor associated antigen (TAA), for early diagnosis of OS.

METHODS

Differential expression of biomarkers in sera from 28 patients with OS and 49 normal human sera were screened by a focused protein microarray with 154 human recombinant proteins. Enzyme-linked immunosorbent assay (ELISA) was applied to validate the three potential biomarkers from 49 OS patients matched with 49 normal controls and 39 osteochondroma. The diagnostic value of each TAA for OS was analyzed by receiver operating characteristic curve. Western blotting and immunohistochemistry were used to verify the results of ELISA.

RESULTS

Based on the protein microarray, three differentially expressed TAAs [G-protein subunit alpha 11, serine/arginine-rich splicing factor 2 (SRSF2), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha] were screened out, whose content was higher than in normal human sera. According to the results of ELISA, anti-SRSF2 autoantibody showed higher expression in OS than in normal controls, with sensitivity, specificity, and area under the curve of 16.33%, 95.92%, and 0.648, respectively. The ELISA results were confirmed by western blotting and immunohistochemistry.

CONCLUSION

Autoantibody is potential serological biomarker in detecting OS. Expression of anti-SRSF2 autoantibody has the potential to distinguish OS from the normal individuals.

Keywords: Osteosarcoma; Tumor associated antigen; Protein microarray; Detection; SRSF2; Biomarker

Core Tip: Osteosarcoma (OS) is, a common malignant tumor, with no specific serological biomarker for early diagnosis. In this study, we focused on identifying novel autoantibodies against tumor associated antigens using the focused protein microarray based on cancer-driving genes for detecting OS. Three tumor associated antigens were identified through the focused protein microarray. Expression of these three autoantibodies was further detected by enzyme-linked immunosorbent assay, which was further validated by western blotting and immunohistochemistry. Serine/arginine-rich splicing factor 2 was identified as a potential serological biomarker for OS, and a possible supplementary screening approach.