Association of elevated autoantibody to high expression of GNAS in hepatocellular carcinoma

Keyan Wang; Cuipeng Qiu; Mengtao Xing; Miao Li; Bofei Wang; Hua Ye; Jianxiang Shi; Liping Dai; Xiao Wang; Peng Wang

doi:10.1016/j.heliyon.2023.e22627

Association of elevated autoantibody to high expression of GNAS in hepatocellular carcinoma

Heliyon. 2023 Nov 20;9(12):e22627. doi: 10.1016/j.heliyon.2023.e22627. eCollection 2023 Dec.

Authors

Keyan Wang^{1

2}, Cuipeng Qiu^{2

3}, Mengtao Xing⁴, Miao Li¹, Bofei Wang³, Hua Ye^{2

3}, Jianxiang Shi^{1

2}, Liping Dai^{1

2}, Xiao Wang^{1

2}, Peng Wang^{2

3}

Affiliations

¹ Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China.
² State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.
³ Department of Epidemiology and Health Statistics & Henan Key Laboratory for Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
⁴ Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.

Abstract

Purpose: This study was based on hepatocellular carcinoma (HCC) patients of early-stage to explore the diagnostic capability and possible production causes of anti-GNAS autoantibody.

Methods: We evaluated the frequency of anti-GNAS autoantibody in sera from patients with early-stage HCC by enzyme-linked immunosorbent assay (ELISA) and the expression of GNAS protein in early-stage HCC tissues by immunohistochemistry. Western blotting (WB) and real-time polymerase chain reaction (RT-PCR) were utilized to examine the expressions of GNAS protein and mRNA in cell lines. GEO and International Cancer Genome Consortium (ICGC) databases were inquired to explore mRNA expression and mutation of GNAS in HCC tissues.

Results: The positive rates of anti-GNAS autoantibody in HCC patients at clinical stage I (78.1 %) and clinical stage II (57.1 %) were all significantly higher than that in healthy control (20 %). There was also a significant difference in GNAS protein expression between HCC and its adjacent normal liver tissues. The results from WB and RT-PCR showed a significant difference at the mRNA level but no statistical difference at the protein level between HCC and normal liver cell lines. The difference in mRNA level between HCC and adjacent normal liver tissues was verified to be significant. Furthermore, the ICGC database demonstrated a 10.6 % mutation frequency for GNAS in HCC patients.

Conclusion: The coordination of elevated anti-GNAS autoantibody, high expression of GNAS in the mRNA and protein levels in HCC, and high frequency of GNAS mutation indicates that anti-GNAS autoantibody may be used as an early indicator of HCC.

Keywords: Autoantibody; Detection; Gene mutation; HCC; Protein expression.