Wang Lingcheng, Song Yinghua, Men Xuelin
Department of Respiratory Medicine, Jinan No.4 People's Hospital, 50 Shifan Road, Jinan, Shandong Province, 250031, China.
Tumour Biol. 2014 Mar;35(3):2319-25. doi: 10.1007/s13277-013-1307-9. Epub 2013 Oct 19.
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) has been recently documented in various malignancies, but its role in non-small cell lung cancer (NSCLC) remains uncertain. In the current study, we investigated the level of TNFAIP8 in NSCLC tissues, adjacent noncancerous lung tissues, healthy lung tissues, CD4+ T cells, and CD8+ T cells by real-time reverse transcription PCR (RT-PCR) and Western blot analysis. Results revealed that the mRNA level of TNFAIP8 was significantly increased in cancer tissue than in healthy lung tissue from donors (p < 0.001). Interestingly, adjacent noncancerous lung tissues also showed higher mRNA level of TNFAIP8 than healthy lung tissue from donors (p < 0.01). Similarly, protein level of TNFAIP8 was elevated in NSCLC tissues and adjacent noncancerous lung tissues. We further analyzed TNFAIP8 expression in CD4+ T cells and CD8+ T cells. Data demonstrated that both mRNA level and protein level were significantly decreased in tumor-infiltrating CD4+ and CD8+ T cells than in peripheral CD4+ and CD8+ T cells. Moreover, patients with advanced stages presented lower protein expression of TNFAIP8 in tumor-infiltrating CD8+ T cells than patients with primary stages (p < 0.05). These results provide evidence that TNFAIP8 plays critical roles in NSCLC and may be used as a therapeutic target for the disease.
肿瘤坏死因子α诱导蛋白8(TNFAIP8)最近在多种恶性肿瘤中被报道,但它在非小细胞肺癌(NSCLC)中的作用仍不明确。在本研究中,我们通过实时逆转录PCR(RT-PCR)和蛋白质印迹分析,研究了TNFAIP8在NSCLC组织、癌旁非癌肺组织、健康肺组织、CD4⁺ T细胞和CD8⁺ T细胞中的水平。结果显示,与供体的健康肺组织相比,癌组织中TNFAIP8的mRNA水平显著升高(p < 0.001)。有趣的是,癌旁非癌肺组织中TNFAIP8的mRNA水平也高于供体的健康肺组织(p < 0.01)。同样,NSCLC组织和癌旁非癌肺组织中TNFAIP8的蛋白水平也升高。我们进一步分析了TNFAIP8在CD4⁺ T细胞和CD8⁺ T细胞中的表达。数据表明,肿瘤浸润的CD4⁺和CD8⁺ T细胞中的mRNA水平和蛋白水平均显著低于外周CD4⁺和CD8⁺ T细胞。此外,晚期患者肿瘤浸润CD8⁺ T细胞中TNFAIP8的蛋白表达低于早期患者(p < 0.05)。这些结果提供了证据,表明TNFAIP8在NSCLC中起关键作用,可能用作该疾病的治疗靶点。