| 摘要: | 肺癌因早期診斷困難及高轉移能力，常年位居國人癌症死因之首。晚期非小細胞肺癌（NSCLC）經化學療法往往收效甚微，第一線使用免疫檢查點抑制劑（ICIs）合併化學療法成為新的治療趨勢。然而部份患者對免疫治療的反應不佳，投入大筆醫藥費換來的卻是更短的壽命以及免疫毒性導致的災難。因此找到更準確的免疫療法療效指標，精準定義適合使用的患者尤為重要。在現行的NCCN治療指引中，PD-L1在腫瘤組織中所佔的比例（TPS）已被做為主要的療效指標，然而臨床觀察卻發現此項指標不夠準確。其他研究發現腫瘤本身的突變負荷量（TMB）、腫瘤基因的微衛星不穩定性（MSI）、基因錯誤配對修復系統的功能（MMR）、腫瘤微環境（TME）中浸潤的免疫細胞（TILs）皆與免疫治療療效具有相關性。我們過去的研究中發現在肺癌細胞上有高表現的CD109，能透過活化Hippo訊息傳遞路徑誘導肺腺癌的上皮細胞間質轉化（EMT）並促進腫瘤轉移。另外在子宮頸癌CD109調控腫瘤生長和侵襲以及PD-L1表現量的能力已被證實。本篇研究進而透過癌症基因組圖譜（TCGA）等多個資料庫分析以及肺癌組織的免疫組織化學染色（IHC），證實CD109在肺癌細胞中與上述多項免疫療效指標如PD-L1表現量、腫瘤突變負荷量、腫瘤內浸潤淋巴球等具有正相關，並有望成為肺癌免疫療法療效的新興生物標記。
Lung cancer is the leading cause of cancer death in Taiwan as it is hard for early diagnosis and shows a high capacity for metastasis. Chemotherapy for advanced non-small cell lung cancer (NSCLC) often achieves little effect. Therefore, the first-line treatment of ICIs combined with chemotherapy has become a new trend. However, some patients have poor response to immunotherapy, and more medical cost investment may result in shorter lifespan and immunotoxicities. Therefore, it is important to find more accurate therapeutic biomarkers to precisely define patients who are suitable for immunotherapy. In the current NCCN guideline, PD-L1 level has been used as the main therapeutic biomarker. However, it is not accurate enough. Other studies have found that tumor mutation burden (TMB), microsatellite instability (MSI) of tumor genes, function of mismatch repair system (MMR), and immune cells infiltrated in the tumor microenvironment (TME) are all related to the efficacy of immunotherapy. Our previous study found that high expression of CD109 in lung cancer cells can induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis through the activation of the Hippo signaling pathway in lung adenocarcinoma. Moreover, in cervical squamous cell carcinoma, CD109 has been shown to regulate tumor growth, invasion, and PD-L1 expression level. This study confirm that CD109 in lung cancer cells is positively correlated with many of the above immunotherapeutic efficacy indicators, such as PD-L1 tumor proportion score (TPS), tumor mutation burden, and tumor-infiltrating lymphocytes, through analyses of multiple databases including The Cancer Genome Atlas (TCGA) and IHC staining of lung cancer tissues, and it is expected to become a novel biomarker for the efficacy of lung cancer immunotherapy. |
