| 摘要: | 肺癌是台灣及全球常見癌症之一，因早期症狀不明顯，導致死亡率居高不下，其中非小細胞肺癌（non-small cell lung cancer, NSCLC）占約85%。空氣污染物如PM2.5被證實為重要致癌因子，提升早期診斷技術有助於改善預後。
外泌體(exosomes)是細胞分泌的雙層膜囊泡，內含蛋白質、脂質、DNA與RNA，能傳遞生物訊號影響其他細胞。癌細胞產生的外泌體與正常細胞不同，常攜帶具腫瘤特異性的分子，能反映病理狀態，是潛力極高的癌症診斷標記。外泌體可自血液、尿液等體液取得，具非侵入性、穩定性高與能克服腫瘤異質性等優勢。越來越多研究指出，外泌體中長鏈非編碼RNA（long non-coding RNAs, lncRNAs）在肺癌早期偵測中扮演重要角色。
南高雄工業區PM2.5嚴重污染，肺癌發病率為全國平均17倍。本研究從文獻中篩選19種與NSCLC相關的外泌體lncRNAs，分析南高雄NSCLC患者血漿樣本，透過qRT-PCR篩檢生物標記，並於A549細胞進行PM2.5暴露實驗，探討PM2.5對lncRNAs表現的影響。
結果顯示，早期肺癌患者血漿外泌體中HAGLR表現顯著下降，具診斷潛力；另有五種lncRNAs（AGAP2-AS1、LINC00662、UFC1、SOX2-OT、GAS5）與HAGLR的表現量比值，在患者中顯著上調（P<0.05）。細胞實驗亦發現PM2.5處理後，FOXD3-AS1與LINC00662表現下降，GAS5上升，顯示空污可調控外泌體lncRNAs的表現。
本研究篩選出六種具潛力的lncRNAs標記，有望成為NSCLC早期診斷工具，提供非侵入性檢測方式，並揭示空氣污染可能透過外泌體分子改變促進肺癌發生，為機制研究與臨床應用提供新方向。
;Lung cancer is one of the most common cancers in both Taiwan and worldwide. Due to the lack of obvious symptoms in the early stages, its mortality rate remains high. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Air pollutants such as PM2.5 have been confirmed as significant carcinogenic factors, and improving early diagnostic techniques is crucial for better prognosis.
Exosomes are double-membrane vesicles secreted by cells, containing proteins, lipids, DNA, and RNA, which mediate intercellular communication. Exosomes derived from cancer cells differ from those of normal cells, often carrying tumor-specific molecules that reflect the pathological state of their origin, making them promising biomarkers for cancer diagnosis. Exosomes can be obtained non-invasively from body fluids such as blood and urine, offering advantages including high stability and the ability to overcome tumor heterogeneity. Increasing evidence suggests that long non-coding RNAs (lncRNAs) within exosomes play important roles in the early detection of lung cancer.
In southern Kaohsiung, a heavily industrialized area with severe PM2.5 pollution, the incidence of lung cancer is 17 times higher than the national average. This study selected 19 NSCLC-associated exosomal lncRNAs based on literature review and analyzed plasma samples from NSCLC patients in southern Kaohsiung using qRT-PCR to identify potential diagnostic biomarkers. Additionally, A549 cells were exposed to PM2.5 to investigate its effects on lncRNA expression.
Results showed that HAGLR expression in plasma exosomes was significantly downregulated in early-stage lung cancer patients, indicating its diagnostic potential. Furthermore, the expression ratios of HAGLR to five other lncRNAs (AGAP2-AS1, LINC00662, UFC1, SOX2-OT, and GAS5) were significantly elevated in patients (P < 0.05). In vitro experiments revealed that PM2.5 exposure reduced the expression of FOXD3-AS1 and LINC00662, while increasing GAS5 expression, suggesting that air pollution can modulate exosomal lncRNA expression.
This study identified six potential lncRNA biomarkers that may serve as non-invasive tools for early NSCLC diagnosis and provides evidence that air pollution may contribute to lung cancer development through exosome-mediated molecular changes, offering new insights for both mechanistic research and clinical applications. |
