Bin-Alee Fardeela, Arayataweegool Areeya, Buranapraditkun Supranee, Mahattanasakul Patnarin, Tangjaturonrasme Napadon, Mutirangura Apiwat, Kitkumthorn Nakarin
Chulalongkorn University, Faculty of Medicine, Department of Anatomy, Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Bangkok, Thailand.
Chulalongkorn University, Faculty of Medicine, Program of Medical Science, Bangkok, Thailand.
J Appl Oral Sci. 2020 Sep 7;28:e20200124. doi: 10.1590/1678-7757-2020-0124.
To evaluate apoptotic levels of peripheral blood mononuclear cells (PBMCs) and apoptotic regulatory proteins (Bax and Bcl-2) in lymphocyte subsets of oral cancer (OC) patients and healthy controls (HC).
The percentage of apoptotic cells and lymphocyte counts were measured in the first cohort using PBMCs obtained from 23 OC patients and 6 HC. In the second cohort, (OC, 33; HC, 13), the mean fluorescence intensity (MFI) of Bax and Bcl-2 in CD19+ B, CD4+ T, CD8+ T, and CD16+56+ natural killer (NK) cells was determined via flow cytometry.
The percentage of apoptotic cells was higher in the PBMCs of OC patients than in HC patients, particularly in patients with stage IV cancer (p<0.05). However, lymphocyte counts were significantly lower in stage IV patients (p<0.05). NK CD19+ B and CD16+56+ cell counts were significantly lower in OC patients compared with HC patients (p<0.001 and p<0.01, respectively), but CD4+ T cells were interestingly significantly higher in OC patients (p<0.001). While Bax MFI was slightly higher, Bcl-2 MFI was significantly lower for all four lymphocyte subsets in OC samples, particularly in stage IV patients, when compared with HC. Consequently, Bax/Bcl-2 ratios showed an upward trend from HC to OC patients, particularly those in stage IV. We found similar trends in Bax and Bcl-2 MFI for tumor stage, tumor size, and lymph node involvement.
The increased lymphocyte apoptosis in stage IV OC patients may be related to higher Bax levels and lower Bcl-2 levels. The Bax/Bcl-2 ratio in lymphocytes may be useful to determine the prognosis of OC patients, and could be considered a mean for supportive treatment in the future.
评估口腔癌(OC)患者和健康对照(HC)外周血单个核细胞(PBMC)的凋亡水平以及淋巴细胞亚群中凋亡调节蛋白(Bax和Bcl-2)的情况。
在第一个队列中,使用从23例OC患者和6例HC获取的PBMC测量凋亡细胞百分比和淋巴细胞计数。在第二个队列中(OC患者33例,HC患者13例),通过流式细胞术测定CD19+B、CD4+T、CD8+T和CD16+56+自然杀伤(NK)细胞中Bax和Bcl-2的平均荧光强度(MFI)。
OC患者PBMC中的凋亡细胞百分比高于HC患者,尤其是IV期癌症患者(p<0.05)。然而,IV期患者的淋巴细胞计数显著更低(p<0.05)。与HC患者相比,OC患者的NK、CD19+B和CD16+56+细胞计数显著更低(分别为p<0.001和p<0.01),但有趣的是,OC患者的CD4+T细胞显著更高(p<0.001)。与HC相比,OC样本中所有四个淋巴细胞亚群的Bax MFI略高,而Bcl-2 MFI显著更低,尤其是IV期患者。因此,从HC到OC患者,尤其是IV期患者,Bax/Bcl-2比值呈上升趋势。我们在肿瘤分期、肿瘤大小和淋巴结受累方面的Bax和Bcl-2 MFI中发现了类似趋势。
IV期OC患者淋巴细胞凋亡增加可能与Bax水平升高和Bcl-2水平降低有关。淋巴细胞中的Bax/Bcl-2比值可能有助于确定OC患者的预后,并可能在未来被视为支持性治疗的一种手段。