Abnormal expression and potential clinical value of oncogenic Krüppel-like factor-5 in lung squamous cell carcinoma

doi:10.5306/wjco.v16.i10.111213

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World Journal of Clinical Oncology

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World J Clin Oncol. Oct 24, 2025; 16(10): 111213
Published online Oct 24, 2025. doi: 10.5306/wjco.v16.i10.111213

Abnormal expression and potential clinical value of oncogenic Krüppel-like factor-5 in lung squamous cell carcinoma

Yang Shi, Wen-Li Sai, Jin-Liang Chen, Li-Wei Qiu, Min Yao, Jun Zhao, Deng-Fu Yao

Yang Shi, Wen-Li Sai, Li-Wei Qiu, Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China

Yang Shi, Department of Thoracic Surgery, Affiliated Yancheng Hospital of Nantong University, Yancheng 226014, Jiangsu Province, China

Jin-Liang Chen, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China

Min Yao, Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China

Jun Zhao, Department of Thoracic Surgery, The First Affiliated Hospital of Suzhou University, Suzhou 215008, Jiangsu Province, China

Co-first authors: Yang Shi and Wen-Li Sai.

Co-corresponding authors: Jun Zhao and Deng-Fu Yao.

Author contributions: Shi Y, Sai WL, and Chen JL conceptualized and designed the research; Qiu LW and Yao M screened patients and acquired clinical data; Sai WL and Chen JL collected blood specimen and performed laboratory analysis; Shi Y and Chen JL collected blood specimen and performed laboratory analysis; Yao DF and Zhao J supervised the study and revised the manuscript; Shi Y, Yao M, Sai WL, Chen JL and Qiu LW constructed the layout of the figures. All the authors read and approved the final manuscript. Shi Y proposed, designed and conducted serum KLF-5 analysis, performed data analysis and prepared the first draft of the manuscript. Chen JL was responsible for patient screening, enrollment, collection of clinical data and blood specimens. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Both Yao DF and Zhao J have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Chen JL applied for and obtained the funds for this research project. Yao DF conceptualized, designed, and supervised the whole process of the project. He searched the literature, revised and submitted the early version of the manuscript with the focus on the association between LUSC and KLF5. Yao DF was instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search, preparation and submission of the current version of the manuscript with a new focus on KLF5 as the predictors of LUSC and on potential underlying mechanisms. This collaboration between Zhao J and Yao DF is crucial for the publication of this manuscript and other manuscripts still in preparation.

Supported by Jiangsu Commission of Health of China, No. M2020096.

Institutional review board statement: The research was carried out in accordance with the most recent version of the Helsinki Declaration and was approved by the Independent Interdisciplinary Ethics Committee for the Affiliated Hospital of Nantong University (No. 2020-L151). Each participant provided informed consent for their involvement in the study and for the publication of anonymized results, after the procedures had been thoroughly explained.

Institutional animal care and use committee statement: Ethical approval for the was provided by the Animal Care and Use Committee of Nantong University (No. S20220221-009), China.

Conflict-of-interest statement: All authors declare that there are no competing interests.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: Databases presented in this study were obtained from online repositories. Data were retrieved from the TCGA (https://www.cancer.gov/tcga), GEPIA (http://GEPIA.cancer-pku.cn), KEGG (https://www.KEGG.jp), GO (http://geneontology.org) and BIOCARTA (https://cn.bing.com/dict/biocarta). The original contributions presented in the study are included in the article, and further inquiries can be directed to the corresponding authors.

Corresponding author: Deng-Fu Yao, MD, PhD, Postdoc, Professor, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong 226001, Jiangsu Province, China. yaodf@ahnmc.com

Received: June 26, 2025
Revised: August 4, 2025
Accepted: September 25, 2025
Published online: October 24, 2025
Processing time: 121 Days and 3.6 Hours

Abstract

BACKGROUND

Krüppel-like factor-5 (KLF5) is a zinc-finger transcription factor related to tumor progression. However, the relationship between KLF5 and lung cancer remains to be identified.

AIM

To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma (LUSC).

METHODS

Lung KLF5 mRNA data were extracted from bioinformatics databases. Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry, Western blot, Enzyme-Linked Immunosorbent Assay or quantitative polymerase chain reaction. Furthermore, KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo, respectively.

RESULTS

A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC (P < 0.001) but lower KLF5 mRNA expression in lung adenocarcinoma. Upregulated KLF5 in the lung or sera of patients with lung cancer (P < 0.001) were confirmed that related to poor differentiation, lymph node or distant metastasis. Furthermore, the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%, which was significantly greater (P < 0.001) than that in cases with benign lung diseases (13.3%) or healthy controls. Functionally, silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation, decreased cell migration, increased the ratio of G2 phase cells in vitro, and inhibited the growth of nude mouse xenografts in vivo.

CONCLUSION

KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.

Keywords: Targeted therapy; Xenograft growth; Biological behaviors; Diagnostic biomarker; Lung adenocarcinoma; Lung squamous-cell carcinoma; Lung cancer; Oncogenic Krüppel-like factor-5

Core Tip: Krüppel-like factor-5 (KLF5) is upregulated in lung cancer, with stronger expression in lung squamous-cell carcinoma (LUSC) than in lung adenocarcinoma. Upregulated KLF5 expression was associated with the proliferation, migration and cell cycle of lung cancer cells, which is likely a favorable diagnostic biomarker of LUSC and could be a new molecular target for lung cancer. Furthermore, KLF5 might exert its oncogenic regulatory effects on the growth of lung cancer by increasing metastasis or progression by activating related signaling pathways.