EBV微RNA-BART20-5p在NK細胞淋巴癌中直接抑制T-bet並間接抑制p53

Abstract

目的： NK/T細胞鼻淋巴癌源自於鼻黏膜，會透過局部的侵入擴散到相鄰的組織，或是遠端轉移到區域性淋巴結。本研究目的主要探討NK/T細胞鼻淋巴癌一旦具侵入性後對預後的影響，以及淋巴癌中細胞毒殺標誌表現與侵入的關聯。 方法與結果： 此研究選擇了64位NK/T細胞鼻淋巴癌病人，利用組織病理學方法去評估侵入之程度及組織免疫染色去看細胞毒殺細胞的標誌的表現，包含了看：ETS-1，T細胞中的T-bet，信息傳遞及活化轉錄因子STAT-1，CD56，granzyme B。其中有17位病人被歸類為無侵入性的第一期（又稱為Ia 或是黏膜型），有21位病人被歸類為侵入性的第一期（又稱為Ib），16位病人被歸類為第二期，10位病人被歸類為第三/四期。第Ia期的病人較Ib期及二、三/四期的病人五年內有較好的存活率（分別是85％，38％，33％，20％）。研究結果發現在第Ia期的病人中ETS-1的表現為24％（4/17），而第Ib及二、三/四期的病人ETS-1的表現為65％（28/43）；而T-bet在Ia期病人表現為29％（5/17），在Ib及二、三/四期病人表現為67％（30/45）。 結論： NK/T細胞鼻淋巴癌為典型的侵襲性淋巴癌，但是黏膜型的侵襲性較低。由實驗中發現，ETS-1及T-bet表現量的減少也與侵襲性低有相關，之後我們也會做其他相關的研究來進一步證實。

Aims: Nasal NK/T-cell lymphoma (NNKTCL) arises from the nasal mucosa, and spreads to adjacent tissues via local invasion or to regional lymph nodes and distant sites via metastasis. We studied the impact of invasion on the prognosis of NNKTCL, and correlated invasion with the expression of cytotoxic markers of lymphoma cells. Methods and Results: Histopathologic evaluations of invasion and immunostains for cytotoxic markers, including EST-1, T-bet, STAT-1, CD56, and granzyme B, were performed in 64 NNKTCLs. There were 17 stage-I cases without invasion (stage Ia or intramucosal), 21 stage-I cases with invasion (stage Ib), 16 stage-II cases, and 10 stage-III/IV cases. Stage-Ia NNKTCLs had a better 5-year overall survival rate than that of stage-Ib, II, or III/IV NNKTCLs (85%, 38%, 33%, and 20%, respectively, p<0.001 by logrank test). Loss of ETS-1 was found in 24% (4/17) stage-Ia NNKTCLs and in 65% (28/43) stage-Ib/II/III/IV NNKTCLs (p=0.04, Fischer’s test); loss of T-bet was found in 29% (5/17) stage-Ia NNKTCLs and in 67% (30/45) stage-Ib/II/III/IV NNKTCLs (p=0.02, Fischer’s test). Conclusions: NNKTCL is classically an aggressive lymphoma, but the intramucosal variant is less aggressive. Loss of ETS-1 or T-bet correlated weakly with invasion, a finding that requires further confirmation.