口腔癌新穎靶點探索的轉錄體整合分析：聚焦於 INHBB

Abstract

口腔癌是全球常見癌症之一，具有高度侵襲性及轉移性，使早期診斷及有效治療成為迫切的研究議題。儘管標靶治療因其高準確性與低副作用逐漸成為癌症治療的重要方向，目前口腔癌治療僅核准少數標靶藥物，且對於靶點蛋白表現不明顯的患者療效有限，因此必須發掘新穎的治療標靶。本研究結合公開單細胞RNA定序資料集分析以及本實驗室先前研究之長期酸化環境對口腔癌細胞影響之成果，透過蛋白質層級的表現量化驗證，探索口腔癌新穎治療標靶及其可能的分子調控機制。研究結果指出，INHBB於口腔癌組織中具有顯著較高的表現比例，且其表現強度與臨床分期高度相關，顯示INHBB具有作為早期診斷及預後評估的潛力，亦透過單細胞RNA定序分析，了解腫瘤微環境中細胞間通訊與高INHBB表達癌細胞之差異表達基因與上游調控因子，並提出假設性腫瘤酸化微環境與INHBB調控模型，為癌症靶點探索提供了新的研究方向。

Oral squamous cell carcinoma (OSCC) ranks among the most prevalent malignancies worldwide and is characterized by pronounced invasiveness and metastatic potential, rendering early diagnosis and effective therapy essential. Although targeted treatments provide high specificity with relatively low toxicity, only a few have been approved for OSCC, and their efficacy is restricted in tumors lacking strong expression of the relevant molecular targets, highlighting the need for novel therapeutic candidates. By integrating single-cell RNA sequencing with prior evidence on the effects of chronic extracellular acidification in OSCC cells and validating findings at the protein level, potential targets and their regulatory mechanisms were interrogated. INHBB was identified as markedly overexpressed in OSCC tissues, with expression intensity strongly correlated with clinical stage, suggesting value as both an early diagnostic biomarker and a prognostic indicator. Single-cell analyses further elucidated cell–cell communication networks, differentially expressed genes, and upstream regulators associated with INHBB-high malignant cells. On this basis, a working hypothesis model is proposed in which an acidified tumor microenvironment modulates INHBB expression, providing a conceptual framework for future target discovery in OSCC.