- 學位論文
復發口腔癌患者之TNF-α與sTNF-RI & II的變化
Expression of TNF-α and its soluble receptors in recurrent oral cancer patients
摘要
近幾年來的各項研究指出，細胞激素對於腫瘤有許多的作用，特別是α型腫瘤壞死因子（TNF-α）。α型腫瘤壞死因子（TNF-α）有兩種接受器，第一型（TNF-RI，p55）與第二型（TNF-RII，p75），分別透過不同的訊號傳遞途徑，表現出的功能也不同，進而影響各種免疫功能、正常生理或病理反應。2004年蘇的研究讓我們曉得sTNF-RII和TNF-α / sTNF-RII比值的表現與口腔癌有密切關係，我們更進一步想要使用縱向臨床研究(longitudinal clinical study)來得知病人的復發有無與細胞激素的相關性。 目的：我們希望藉由監控血液的TNF-α、sTNF-RI、sTNF-RII來提早得知罹患口腔癌患者的復發有無及預後情形。 方法：我們將24位第一次得到口腔癌患者分別於『術前』、『術後一週』、『術後一月』、『術後三月』、『術後六月』五個時間點與5位口腔黏膜健康的對照組中，抽取周邊靜脈血液分離出單核細胞培養，並以酵素免疫法測定單核細胞分泌之TNF-α、soluble TNF-α receptor I、soluble TNF-α receptor II三種cytokine，並將口腔癌病人分為『未復發』、『復發』兩組來討論相關性。 結果：由『未復發』、『復發』兩組來討論，觀察到『復發』這組在術後一個月的sTNF-α Receptor II分泌濃度高於『未復發』組，且達顯著差異（552.9±106.5>308.1±63.4, p<0.05）；在TNF-α/sTNF-RII比值方面，術前抽血發現『復發』組患者比值顯著低於『未復發』組的患者（0.5±0.1<1.9±0.5, p<0.01），另外由sTNF-RII/sTNF-RI比值來看，『復發』這組分別在術後一週、術後六個月的sTNF-RII/sTNF-RI比值顯著高於『未復發』組（18.5±5.3 > 7.4±1.3 , p < 0.01）（13.1±2.9 > 5.4±0.8 , p < 0.01）。另外由『疾病組』與『對照組』兩組來看，TNF-α的分泌濃度：以Wilcoxon/Kruskal-Wallis Tests無母數分析，觀察到『疾病組』TNF-α分泌濃度高於『對照組』，且達顯著差異（287.8±60.6 > 14.7±6.3, p < 0.01）；另外觀察sTNF-α Receptor I與sTNF-α Receptor II的分泌濃度，『疾病組』與『對照組』在統計上未達顯著差異。 結論：這個研究發現口腔癌患者在手術去除病灶後發現復發的情況時，其sTNF-RII濃度於術後一個月高於未復發的患者；在sTNF-RII/sTNF-RI比值方面，復發患者於術後一週與術後六個月高於未復發的患者；此外我們觀察到TNF-α分泌濃度在疾病組顯著高於對照組。由我們研究結果發現，口腔癌患者之術後一個月的sTNF-RII濃度或利用術前TNF-α/sTNF-RII的比值以及術後一週與術後六個月sTNF-RII/sTNF-RI比值的表現，或許可以用來作為臨床上診斷和預測口腔癌是否復發的參考數據。
並列摘要
Backgroud and objectives: Cytokines, especially TNF-α and its TNF-Rs, have a lot of effect upon tumor development. Recent researches have shown that the measurement of TNF-α and its sTNF-Rs may aid in the evaluation of immune status of cancer patients. According to Su’s previous study, we found that the expression of sTNF-RII and the ratio of TNF-α/sTNF-RII may be used as supplementary information to diagnose high risk and/or suspected OSCC patients. This longitudinal study tried to predict the recurrence of oral cancer by the expression of TNF-?? and sTNF-Rs. Method: The present study collected PBMC samples from 24 subjects with oral squamous cell carcinoma (OSCC) or verrucous carcinoma at different time points before and after treatment, including pre-operation (pre-OP), one week after operation (post-OP 1 week), one month after operation (post-OP 1 month), three months after operation (post-OP 3 months), six months after operation (post-OP 6 months). Five healthy subjects without any oral mucosal disease were used as normal controls. Oral cancer patients were further subdivided into two groups: recurrence (REC) and non-recurrence (NREC) groups. We used enzyme-linked immunosorbent assay (ELISA) to quantify the expression of TNF-α and its sTNF-Rs. Result: We found that the average concentration of sTNF-RII in the recurrence group was significant higher than that in the non-recurrence group at one month after operation. (552.9±106.5>308.1±63.4, p< 0.05) The ratio of sTNF-RII/sTNF-RI in the recurrence group was significant lower than that in the non-recurrence group prior to the operation (0.5±0.1<1.9±0.5, p<0.01) Moreover, the ratio of sTNF-RII/sTNF-RI in the recurrence group was significant higher than that in the non-recurrence group one week and six months after the operation. (18.5±5.3 > 7.4±1.3, p <0.01) (13.1±2.9 > 5.4±0.8, p<0.01) Furthermore, the average TNF-α concentration in the disease group was significant higher than that in the control group (287.8±60.6 > 14.7±6.3, p<0.01), but there was no significant difference in the mean concentrations of sTNF-Rs between the disease and control groups. Conclusion: We conclude that the serum sTNF-RII concentration one month after the operation, the ratio of TNF-α/sTNF-RII prior to the operation and the ratio of sTNF-RII/sTNF-RI one week and six months after the operation may be used to predict the recurrence of oral cancer in those oral cancer patients receiving operation.