대장암과 선종 병변에서 mTOR 신호 단백질의 면역조직화학 염색성 평가 Evaluation of the Immunohistochemical Staining Pattern of the mTOR Signaling Proteins in Colorectal Cancers and Adenoma Lesions원문보기
mTOR신호전달 단백질의 변화는 다양한 종류의 암에서 관찰 되었다. 따라서 이들 단백질은 최근에 암 치료제에 대한 새롭고 흥미로운 표적이 되고 있다. 우리는 대장암과 선종 환자의 mTOR 세포신호의 활성도를 조사하였다. 면역조직화학적 방법으로 대장암과 선종의 세포신호 단백질 성분인 mTOR, p70-S6K, S6, 4EBP1 발현을 분석하였다. 이번 연구는 모두 100개의 예를 악성(Colorectal Adenocarcinoma, CRAC) 40건, 고등급 선종(Adenoma with High grade intraepithelial neoplasms, HIN) 30건, 저등급 선종(Adenoma with Low-grade intraepithelial neoplasms, LIN) 30건으로 분류하여 진행하였다. p-mTOR의 발현률은 LIN 7%, HIN 30%, CRAC 75%였고 p-S6의 발현률 또한 LIN 10%, HIN 27%, CRAC 55%였다. p-mTOR, p-S6의 발현과 선종-선암 연속성은 중요한 상관관계 있다는 것이 발견되었다. 그리고 흥미롭게도 p-S6 발현률은 진행암보다 초기암에서 더 높았다.
mTOR 신호전달 단백질의 변화는 다양한 종류의 암에서 관찰 되었다. 따라서 이들 단백질은 최근에 암 치료제에 대한 새롭고 흥미로운 표적이 되고 있다. 우리는 대장암과 선종 환자의 mTOR 세포신호의 활성도를 조사하였다. 면역조직화학적 방법으로 대장암과 선종의 세포신호 단백질 성분인 mTOR, p70-S6K, S6, 4EBP1 발현을 분석하였다. 이번 연구는 모두 100개의 예를 악성(Colorectal Adenocarcinoma, CRAC) 40건, 고등급 선종(Adenoma with High grade intraepithelial neoplasms, HIN) 30건, 저등급 선종(Adenoma with Low-grade intraepithelial neoplasms, LIN) 30건으로 분류하여 진행하였다. p-mTOR의 발현률은 LIN 7%, HIN 30%, CRAC 75%였고 p-S6의 발현률 또한 LIN 10%, HIN 27%, CRAC 55%였다. p-mTOR, p-S6의 발현과 선종-선암 연속성은 중요한 상관관계 있다는 것이 발견되었다. 그리고 흥미롭게도 p-S6 발현률은 진행암보다 초기암에서 더 높았다.
Changes in the mammalian target of the rapamycin (mTOR) signaling proteins have been observed in many types of cancer. Accordingly, these proteins have recently become an exciting new target for molecular therapeutics. This study examined the expression of an activated mTOR signaling protein in pati...
Changes in the mammalian target of the rapamycin (mTOR) signaling proteins have been observed in many types of cancer. Accordingly, these proteins have recently become an exciting new target for molecular therapeutics. This study examined the expression of an activated mTOR signaling protein in patients with colorectal adenocarcinoma (CRAC) and colorectal adenoma lesion. Immunohistochemical analysis was performed on human CRAC and adenoma for the mTOR signaling components, including mTOR, phosphorylation, and activation of S6 kinase (p70-S6K), S6 ribosomal protein (S6), and eukaryotic initiation factor 4E-binding protein (4EBP1). A total of 100 cases with colorectal adenocarcinoma (CARC; N=40), adenoma with high-grade intraepithelial neoplasms (HIN; N=30), and adenoma with low-grade intraepithelial neoplasms (LIN; N=30) were enrolled in this study. p-mTOR expression was observed in 30 cases of the CRAC tissues (75%), 9 cases of adenoma with HIN (30%), and 2 cases of adenoma with LIN (7%). In addition, p-S6 expression was observed in 22 cases of CRAC tissues (55%), 8 cases of adenoma with HIN (27%), and 3 cases of adenoma with LIN (10%). A significant correlation was observed among the p-mTOR, p-S6 expression, and the adenoma-carcinoma sequence. Interestingly, the p-S6 protein was activated more in early CRAC than in advanced CRAC.
Changes in the mammalian target of the rapamycin (mTOR) signaling proteins have been observed in many types of cancer. Accordingly, these proteins have recently become an exciting new target for molecular therapeutics. This study examined the expression of an activated mTOR signaling protein in patients with colorectal adenocarcinoma (CRAC) and colorectal adenoma lesion. Immunohistochemical analysis was performed on human CRAC and adenoma for the mTOR signaling components, including mTOR, phosphorylation, and activation of S6 kinase (p70-S6K), S6 ribosomal protein (S6), and eukaryotic initiation factor 4E-binding protein (4EBP1). A total of 100 cases with colorectal adenocarcinoma (CARC; N=40), adenoma with high-grade intraepithelial neoplasms (HIN; N=30), and adenoma with low-grade intraepithelial neoplasms (LIN; N=30) were enrolled in this study. p-mTOR expression was observed in 30 cases of the CRAC tissues (75%), 9 cases of adenoma with HIN (30%), and 2 cases of adenoma with LIN (7%). In addition, p-S6 expression was observed in 22 cases of CRAC tissues (55%), 8 cases of adenoma with HIN (27%), and 3 cases of adenoma with LIN (10%). A significant correlation was observed among the p-mTOR, p-S6 expression, and the adenoma-carcinoma sequence. Interestingly, the p-S6 protein was activated more in early CRAC than in advanced CRAC.
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제안 방법
We investigated the correlation between the CRAC parameters and the p-mTOR or p-S6 expression by using Fisher's exact test (Table 5). The CRAC parameters included age, gender, depth, and lymph node metastasis. A relationship was found between depth and p-S6 expression (p＜0.
However, cell signal change was not analyzed in previous studies. Thus, this study aimed to evaluate the expression of cell signaling proteins, namely, p-mTOR, p70-S6K, p-S6, and p-4EBP1, in colorectal cancer tissues and the corresponding benign adenoma lesion in the colon.
대상 데이터
This study retrospectively examined surgical pathology data of SC Hospital in Changwon city from January 2011 to March 2012. FFPE (formalin fixed paraffin embedded) colon tissue samples, which were found to be adenoma with low-grade intraepithelial neoplasms (LIN; N=30), adenoma with high-grade intraepithelial neoplasms (HIN; N=30), and colorectal adenocarcinoma (CRAC; N=40), were selected.
This study retrospectively examined surgical pathology data of SC Hospital in Changwon city from January 2011 to March 2012. FFPE (formalin fixed paraffin embedded) colon tissue samples, which were found to be adenoma with low-grade intraepithelial neoplasms (LIN; N=30), adenoma with high-grade intraepithelial neoplasms (HIN; N=30), and colorectal adenocarcinoma (CRAC; N=40), were selected.
데이터처리
Correlations between markers were calculated using the Pearson’s correlation coefficient along with tests for significance.
The comparison between p-mTOR or p-S6 activity and the clinical parameter was made by the Fisher’s exact test.
We investigated the correlation between the CRAC parameters and the p-mTOR or p-S6 expression by using Fisher's exact test (Table 5).
We then analyzed the relationship between p-mTOR and p-S6 or p-4EBP1 activities using the Pearson’s correlation coefficient test in adenomas to CRACs (Table 4).
성능/효과
All 100 cases of colorectal lesions were classified by pathologic stage and examined by histological type, tumor size, gender, and age. The polyp or tumor mean size and age were the greatest in the group of advanced CRAC.
In this study, we showed for the first time that the p-mTOR expression was much higher in CRAC (75%) than in either paired HIN (30%) or LIN (7%). Also the p-S6 expression rate was similar to that.
For the last time, we utilized the clinical significance of p-mTOR and p-S6 expressions in CRACs. This study obtained a unique result: p-S6 expression was significantly related to a small invasion depth. That is, the S6 proteins had low activity in the progress toward CRAC.
후속연구
Several studies have shown a slightly different result from the increase in p-4EBP1, which frees eIF4E to promote protein translation in cancer [18,19]. Future research is needed to confirm our findings and to identify the 4EBP1 activation mechanism and the potential pathogenic role in CRAC.
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