| 摘要: | 頭頸部鱗狀上皮細胞癌(以下稱為 HNSCC) 在全球都是重要的健康問題之一。手術、放射、以及化學治療目前是HNSCC 患者的標準治療。病患的存活必須仰賴: 1)足夠(大)的手術切緣、病理報告指引的放射治療，2)系統性治療(標靶、免疫療法)的「生物標記」，以及3)全人癌症照護(顧及靈性須求、身體照護、心理支持，與社會支援)。HNSCC癌症存活分析在傳統上，是利用組織中基因表現量的差異(DEGs)，以臨床資訊搭配蛋白質體的數據，來找尋生物標記。而採用HNSCC全基因表現量、結合存活分析的方法，則首見於2021年發表的「pvalueTex」。本文介紹質譜法分析HNSCC，以及pvalueTex的處理流程，包括數據檢索、前製處理、特徵選擇、「無段式」閾值分析、Kaplan--Meier存活分析，和Cox比例風險模型。
我們依此發現，HNSCC的獨立預後因子為: 生物標記（TMSB4X、CAMK2N1、CALML5 和FCGBP）、腫瘤大小，以及手術切緣狀態。由總存活期 (OS) 、無復發存活期(RFS)較差的的患者檢體中，可以發現大量表現的TMSB4X蛋白。實驗中發現，若抑制HNSCC細胞株中的TMSB4X，其細胞增殖速率會減少，且降低小鼠的頸部淋巴結轉移，證明TMSB4X與HNSCC的頸部轉移有高度相關。至於CAMK2N1、CALML5和FCGBP基因的表現量，則與患者的總存活期(OS)密切相關。
我們必須推廣全人癌症照護的觀念，強調靈性、精神、情感、身體和社會關係層面，對癌症患者存活的重要影響。全人癌症照護結合有效的生物標記，終將成為真正量身定製的個人化治療。
Head and neck squamous cell carcinoma (HNSCC) represents a significant health concern worldwide. Surgery and chemo-radiotherapy are still the standard of care for HNSCC patients. The breakthrough improvement of those interventions should depend on 1) adequate surgical margin and radiotherapy guided by pathology, 2) predictive biomarkers, which are guiding a systemic therapy, and 3) holistic cancer care. The survival analysis could conclude the manifest of clinical and multiple omics data to find high-impact biomarkers. To discover cancer biomarkers, we use mass spectrometry method to analyze HNSCC. Traditionally, differential gene expression in HNSCC has been exploited to detect biomarkers.
Global gene expression incorporated with survival analysis of HNSCC are employed for the first time in 2021, to the best of our knowledge.
Data retrieval and pre-processing, feature selection, sliding-window cutoff selection, Kaplan—Meier estimate, and Cox proportional hazard regression model are all part of the "pvalueTex" in-house workflow. It could be utilized to find predictive biomarkers of surgical margins and to provide holistic cancer therapy. Four validated biomarkers (TMSB4X, CAMK2N1, CALML5, and FCGBP), clinical tumor size, and surgical margin status all are independent prognosis factors in HNSCC. Overexpression of TMSB4X is associated with a poor prognosis of overall survival (OS) and recurrence-free survival (RFS) of those patients. TMSB4X knockdown in the HNSCC cell line reduced proliferation, invasion, and cervical lymph node metastasis in vitro and in vivo. More- over, CAMK2N1, CALML5, and FCGBP, are also substantially linked with patients’ OS. Holistic cancer care considers the importance of the spirit, emotion, body, and social relationships. Ultimately, holistic cancer therapy will be a comprehensive tailored personalized medication. |
