微小核酸-29C/類二型賴氨酸氧化酶於肺腺癌之診斷治療意義

肺腺癌的早期精準診斷以及其抗藥性的生成一直是臨床上的挑戰。近年來發現 到微核酸 29C 以及類二型賴氨酸氧化酶分別扮演的抑癌以及促癌角色。然而,微核 酸 29C/ 類二型賴氨酸氧化酶軸線的臨床意義以及生物功能尚未釐清。本研究應用 多體學策略探討微核酸 29C/ 類二型賴氨酸氧化酶軸線是否可作為肺腺癌預測模組以 及作為治療標的的潛力。自 cBioPortal 伺服器擷取 7,561 件肺腺癌檢體中,微核酸 29C 的突變光譜展現隨機分布,擴增率僅 3%,且基因套數變化不影響病人存活時 間。相比之下,低表達微核酸 29C 與短存活時間顯著相關,且與類二型賴氨酸氧化 酶呈現負相關。高表達類二型賴氨酸氧化酶與短存活時間顯著相關,並且與 CD8 陽 性 T 細胞呈現負相關,而與癌相關纖維母細胞呈現正相關,顯示出抑制免疫的腫瘤 微環境特徵。此外,微核酸 29C 與臨床分期呈現負向關聯性。TargetScan 生資工具 預測出微核酸 29C 的 3’ 端可標靶類二型賴氨酸氧化酶的兩處 3’ 端未轉譯區,核苷 酸位序 555-561 以及 757-763,表明微核酸 29C 有抑制類二型賴氨酸氧化酶的潛力。 總結本研究發現低表達微核酸 29C 連同高表達類二型賴氨酸氧化酶可預測肺腺癌不 良預後。微核酸 29C/ 類二型賴氨酸氧化酶軸線指出一肺腺癌新生物路徑以及治療 標的。  The early, precise diagnosis and drug resistance of lung adenocarcinoma (LUAD) remains a challenging issue. The tumor suppression role of microRNA- 29C (MIR29C) and the tumor promotion role of lysyl oxidase-like 2 (LOXL2) have recently been observed. However, the clinical implication and biological function of MIR29C/lysyl oxidase-like 2 (LOXL2) axis remains unclear. In this study, we utilized the multi-omic approach to investigate whether the MIR29C/LOXL2 axis can serve as a prediction panel and determine its potential as therapeutic targets. Using the cBioPortal server, the mutation landscape of MIR29C in LUAD samples showed that the mutation spectrum presented a random distribution and the amplification rate was as low as 3%, while LOXL2 presented as 6%. The copy number alteration of MIR29C had no effect on the overall survival (OS) rate, whereas that of LOXL2 was associated with poor OS. In contrast, the low expression of MIR29C was significantly associated with shorter OS. MIR29C negatively correlated with LOXL2 mRNA level. High expression of LOXL2 was significantly associated with shorter OS, and connected with lower infiltration levels of CD8+T cells and higher infiltrate levels of cancer associated fibroblast, representing hallmarks of an immunosuppressive tumor microenvironment. In addition, MIR29C showed a negative association with advanced stages. Using TargetScan Release 7.2, MIR29C-3p was predicted to target LOXL2 3’UTR at position 555-561 and position 757-763, suggesting its inhibitory potential on LOXL2 expression. In summary, this study revealed that low expression of MIR29C and high expression of LOXL2 predict poor outcomes for LUAD patients. The MIR29C/LOXL2 axis may point out a new biological pathway that could be a potential therapeutic target for LUAD.