臺灣博碩士論文加值系統

國外的論文指出EGFR的表現量與和intron 1上的CA重覆片段多型性 (CA SSR1) 在口腔癌中可以作為病人的預後標記，也知道EGFR單一核甘酸多型性 (SNP) -191、-216與CA SSR1會影響EGFR蛋白質表現量，或許這些多型性標記更可以作為有用的臨床預後因子。並且KRAS上codon 12、13的突變會影響大腸癌、非小細胞肺癌病人使用EGFR標靶藥物的療效，即若KRAS有突變存在，會使病人的預後以及用藥的反應都呈現較差的情況，故本實驗欲探討國人這些分子標記的情況，並進一步分析是否可作為口腔癌風險預測因子或臨床預後標記。樣本取自於台中榮民總醫院口腔外科的50對口腔癌病人成對的腫瘤檢體以及來自員生醫院的84個健康個體的血液檢體作為對照組，實驗以ABI 3100進行定序反應以及Gene Scan實驗分析，以確認EGFR SNP -191、-216與CA SSR1的情況以及KRAS基因上是否有突變情況或SNP存在。整體而言，個體若EGFR SNP-216呈現G/T形式會伴隨CA SSR1帶有較少的重覆數 (p < 0.001)，並且OSCC的病人在CA SSR1有明顯的等位基因失衡 (allelic imbalance, AI) 的情況，其基因型也有差異存在，其中病人帶有較高的CA SSR1異結合型比例，而另一方面在KRAS中找到兩個SNP的存在 (rs1137282、rs712)，而在病人與正常對照組中，也發現其比例的不同。以統計分析發現CA SSR1為異結合型的情況，罹患口腔癌的風險為同結合型的2.34倍 (p = 0.04)，且發現rs712若帶有G/T或T/T形式的個體為G/G形式的0.28倍 (p = 0.002)，並且rs712若帶有G/G及CA SSR1為異結合型的風險為rs712帶有G/T或T/T及CA SSR1為同結合型的14.63倍 (p = 0.01)，因此，KRAS的SNP rs712及EGFR的CA SSR1可能可以分別或結合為罹患OSCC的風險因子。另外發現CA SSR1為同結合型的病人預後比起異結合性的病人要來的差 (p = 0.001)，且等位基因失衡的情況也可以作為區分病人預後情況的指標 (p = 0.001)，故發現CA SSR1的變異可以做為台灣地區OSCC病人很有用的預後標記。

It has been reported that the expression of EGFR and EGFR CA SSR1 repeat numbers in tumors can be useful prognosis factors in several cancer types. In addition, two SNPs (-216G/T and -191C/A) in the EGFR promoter may be associated with altered promoter activity and expression of EGFR, implying that the SNPs might be prognosis factors as well. The patients of colon cancer and lung cancer with mutations on KRAS codon 12 and 13 always come with poor prognosis while treating with Gefitnib or Erlotinib. The objective of the present study was to analyze if EGFR polymorphism, KRAS polymorphism and mutations can be useful prognosis factors or risk factors in OSCC in Taiwanese population. Fifty OSCC tissues were collected by surgical excision. The healthy blood samples were collected form 84 individuals. The sequencing and genotyping of EGFR and KRAS were performed with ABI Prism 3100. The results suggested that both the status of CA SSR1 and SNP rs712 might be useful risk factors for OSCC in Taiwan. OSCC patients, who were homozygous for CA SSR1, revealed poor prognosis than those who were heterozygous (p = 0.001). Besides, patients with allelic imbalance of CA SSR1 came with significant lower overall survival rates than those without by the Kaplan–Meier method (p = 0.001), suggesting that the status of CA SSR1 had potential to be useful prognosis factor in of OSCC.

Abstract (Chinese) ………………………………………………… i
Abstract………………………………………………………………… ii

Part 1:
(The Status of EGFR CA SSR1 is a Potential Prognostic Factor for Patients with Oral Squamous Cell Carcinoma)01
Abstract ……………………………………………………………… 02
Chapter 1. Introduction ………………………………………… 03
Chapter 2. Materials and Methods …………………………… 07
Chapter 3. Results ………………………………………………… 11
Chapter 4. Discussion ………………………………………………16
Chapter 5. Reference ……………………………………………… 20
Chapter 6. Tables …………………………………………………… 27
Chapter 7. Figures ………………………………………………… 32

Part 2:
Page#
(A Single Nucleotide Polymorphism of KRAS Might Decrease the Risk of Oral Squamous Cell Carcinoma) ………………… 38
Abstract ………………………………………………………………… 39
Chapter 1. Introduction …………………………………………… 40
Chapter 2. Materials and Methods ……………………………… 44
Chapter 3. Results …………………………………………………… 47
Chapter 4. Discussion ……………………………………………… 50
Chapter 5. Reference ……………………………………………… 54
Chapter 6. Tables …………………………………………………… 62
Chapter 7. Figures ………………………………………………… 68

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