The SOX4–PTBP2 Axis Promotes Proliferation, Invasion and Lymphatic Metastasis in Laryngeal Squamous Cell Carcinoma

Background Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor in otorhinolaryngology, with a high incidence rate and a tendency of lymph node metastasis. This study aims to systematically evaluate the expression of the transcription factor SOX4 in LSCC and its clinical relevance, clarify its impact on the biological behavior of tumors and potential molecular mechanisms, and provide a theoretical basis for diagnosis and treatment. Method Bioinformatics analysis was conducted based on the GEO dataset (GSE201777) to evaluate the expression of SOX4 and its clinical relevance; The expression of SOX4 in LSCC clinical tissues and cell lines was verified by qRT-PCR. SOX4 knockdown and overexpression cell models were constructed. Proliferation was evaluated by MTS and colony formation assays, migration and invasion were evaluated by scratch and Transwell assays, and apoptosis was detected by flow cytometry and TUNEL. The downstream effector molecules of SOX4 were screened by transcriptome sequencing and verified by functional recovery experiments. The association between SOX4 and tumor immune infiltration as well as drug sensitivity was explored by combining bioinformatics analysis. Ultimately, the effects of SOX4 on tumor growth and lymph node metastasis in vivo were evaluated in a xenograft mouse model. Result Bioinformatics and experimental data consistently showed that SOX4 was upregulated in LSCC and positively correlated with disease progression and lymph node metastasis. In vitro experiments have shown that knockdown of SOX4 significantly inhibits the proliferation, migration and invasion of LSCC cells, while overexpression of SOX4 promotes a malignant phenotype. Transcriptome and functional verification determined that PTBP2 is a downstream effector molecule of SOX4. The restored expression of PTBP2 can partially alleviate the inhibitory effect caused by SOX4 knockdown. Bioinformatics analysis further suggests that the SOX4/PTBP2 axis is associated with the tumor immune microenvironment and the sensitivity to several anti-cancer drugs. In vivo studies have shown that knockdown of SOX4 or administration of erlotinib significantly inhibited tumor growth and reduced the rate of lymph node metastasis. Conclusion SOX4 promotes the growth and lymph node metastasis of LSCC by regulating PTBP2. The SOX4-PTBP2 axis may become a potential diagnostic and therapeutic target for LSCC.