Revealing the oncogenic role of elevated GNL3L expression in esophageal squamous cell carcinoma: insights into the STAT3 pathway

Shaobin Yu; Peipei Zhang; Shaojun Xu; Zhang Xiang; Ankit Madan; Guy D Eslick; Farshid Dayyani; Shuchen Chen

doi:10.21037/jtd-24-473

Revealing the oncogenic role of elevated GNL3L expression in esophageal squamous cell carcinoma: insights into the STAT3 pathway

J Thorac Dis. 2024 Apr 30;16(4):2580-2590. doi: 10.21037/jtd-24-473. Epub 2024 Apr 29.

Authors

Shaobin Yu^#¹, Peipei Zhang^#¹, Shaojun Xu^#¹, Zhang Xiang², Ankit Madan³, Guy D Eslick⁴, Farshid Dayyani⁵, Shuchen Chen^{1

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Affiliations

¹ Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
² Department of Pathology, Pingtan Branch of Fujian Medical University Union Hospital, Fuzhou, China.
³ Department of Internal Medicine, Medstar Southern Maryland Hospital Center, Clinton, MD, USA.
⁴ The Australian Paediatric Surveillance Unit (APSU), The University of Sydney, The Children's Hospital, Westmead, New South Wales, Australia.
⁵ Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA, USA.
⁶ Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China.
⁷ Key Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Science, Fujian Medical University, Fuzhou, China.
⁸ Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.

^# Contributed equally.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) patients carries a poor prognosis, with limited effective therapeutic targets. This study aimed to clarify the clinical significance of guanine nucleotide-binding protein like 3-like (GNL3L) protein expression in ESCC and its role in malignant progression.

Methods: GNL3L expression and associated cancer-promoting pathways in ESCC were interrogated via bioinformatics analysis through use of The Cancer Genome Atlas (TCGA) database. Subsequent verification of GNL3L protein expression in ESCC, coupled with clinical data, was conducted through immunohistochemistry and followed by a comprehensive prognostic analysis. We further investigated potential signaling pathways facilitating ESCC progression, employing a combination of bioinformatics analysis and immunohistochemical (IHC) experiments.

Results: Bioinformatics analysis unveiled a significant elevation in GNL3L expression, particularly in gastrointestinal tumors and ESCC. Immunohistochemistry confirmed elevated GNL3L expression in ESCC tissues. Regression analysis established a correlation between elevated GNL3L expression and advanced tumor node metastasis (TNM) stage, with high expression associated with poor prognosis in patients with ESCC. Our integrated approach of bioinformatics and IHC analysis indicated a potential role of the signal transducers and activators of transcription 3 (STAT3) signaling pathway in ESCC progression.

Conclusions: High GNL3L expression significantly contributes to the malignant progression of ESCC. This study further elucidates the mechanisms driving ESCC progression and offers possible insights for more effective diagnosis and treatment strategies.

Keywords: Guanine nucleotide-binding protein like 3-like (GNL3L); clinical significance; esophageal squamous cell carcinoma (ESCC); malignant progression; signal transducers and activators of transcription 3 (STAT3).