KLF15 Transcription Activated Tachykinin Precursor 1 to Induce Perineural Invasion in Head and Neck Squamous Cell Carcinoma

Objective: In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC). Methods: The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR. Results: A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC. Conclusion: This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells. conclusion: This study highlights TAC1 as a PNI biomarker in HNSCC, and shed light on guiding molecular diagnosis of PNI in HNSCC.