卵巢癌是常見的婦科癌症之一，其死亡率最高，大多數的卵巢癌患者確診時已經是疾病晚期且大約有70%的病人會因為抗藥性而發生復發，而高復發率就是造成卵巢癌死亡率高的原因。因此，尋求卵巢癌的治療靶點以及診斷生物標誌物是非常需要的。最近有許多研究報告指出CD24在許多癌症中具有高表現包含卵巢癌。而CD24是最近新發現的免疫檢查點，其為高度醣基化且藉由糖磷脂醯肌醇固定在細胞膜上的表面蛋白質，其會藉由跟腫瘤相關巨噬細胞的Siglec-10受體結合來躲避免疫細胞攻擊。但是，CD24在卵巢癌細胞的內在功能尚未完全清楚。因此本實驗的目的是想探討CD24在卵巢癌進展中所扮演的角色及其作用分子機制。在本篇研究中，我們使用患者生存分析工具Kaplan-Meier plotter來分析網路上的公共數據集，結果顯示當CD24高表現時，卵巢癌病人會有較差的生存率以及較短的復發時間。此外，我們也進行細胞方面的功能測試，對於內生性CD24高表現的TOV21G以及SKOV3細胞使用shRNA將CD24表現量降低並進一步分析癌細胞功能，結果顯示降低CD24表現量會減少細胞增生能力且會使細胞對於抗癌藥物順鉑較敏感。更進一步的分子機制實驗表明CD24表現量降低後，會抑制細胞週期從S phase進入G2/M phase來減少細胞增生;且會藉由促進自噬反應誘導的細胞死亡來增加順鉑藥物敏感性。此外，我們使用生物訊息學工具GSEA來分析TCGA數據集，結果顯示在卵巢癌患者中，CD24會與細胞增生及自噬反應相關的訊息傳遞路徑有關係。且在小鼠皮下注射人類卵巢癌細胞的實驗中，我們也發現降低CD24的表現量會減少小鼠腫瘤生長。總而言之，我們的研究結果表明CD24會調節卵巢癌細胞的生長和抗藥性。

Ovarian cancer is one of the most common gynecological cancers with the highest mortality rate. Most patients are diagnosed with advanced disease and almost 70% of them will relapse due to drug resistance. High recurrence rates of ovarian cancer result in high mortality rates. It is urgent to identify therapeutic targets and diagnostic biomarkers for ovarian cancer. Recently studies showed that CD24 was significantly upregulated in various cancers including ovarian cancer. CD24 is a highly glycosylated and a GPI-anchored membrane protein which is a novel discovered immune checkpoint protein that contributed to cancer immune evasion through binding the Siglec-10 receptors on the tumor-associated macrophages. However, the tumor cell-intrinsic functions of CD24 in ovarian cancer remain unclear. Therefore, our objectives are to investigate the role of CD24 in ovarian cancer progression and its molecule mechanism. In this study, Kaplan-Meier plotter analysis of online public dataset showed that higher CD24 expression was associated with poor survival and recurrence of ovarian cancer patients. Moreover, functional assay in ovarian cancer cells showed that silenced of CD24 by shRNAs in which express high levels of endogenous CD24 cells decreased cell growth and increased drug sensitivity to cisplatin in TOV21G and SKOV3 cells. Further mechanism experiments revealed that knockdown of CD24 reduced cell growth by inhibiting the cell cycle progression from S to G2/M phase while increased cisplatin sensitivity by promoting the autophagy-induced cell death. In addition, GEAS analysis of TCGA dataset showed that CD24 was correlated with cell proliferation and autophagy-related signaling pathway in ovarian cancer patients. In a mice xenograft model, knockdown of CD24 reduced cell growth in vivo. In conclusion, our findings suggested that CD24 regulated cell growth and drug resistance in ovarian cancer cells.

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