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標題Title: Prognostic significance of multiple molecular markers for patients with stage II colorectal cancer undergoing curative resection
作者Authors: 溫義輝,Lin SR..等
上傳單位Department: 生物科技系
上傳時間Date: 2009-11-20
上傳者Author: 溫義輝
審核單位Department: 生物科技系
審核老師Teacher: 溫義輝
檔案類型Categories: 論文Thesis
關鍵詞Keyword: colorectal cancer, prognosis
摘要Abstract: Objective: The aim of this study was to determine whether our
constructed high-sensitivity colorimetric membrane-array method
could detect circulating tumor cells (CTCs) in the peripheral blood
of stage II colorectal cancer (CRC) patients and so identify a
subgroup of patients who are at high risk for relapse.
Summary Background Data: Adjuvant chemotherapy is not routinely
recommended in patients diagnosed with UICC stage II CRC.
However, up to 30% of patients with stage II disease relapse within
5 years of surgery from recurrent or metastatic disease. The identification
of reliable prognostic factors for high-risk stage II CRC
patients is imperative.
Methods: Membrane-arrays consisting of a panel of mRNA markers
that included human telomerase reverse transcription (hTERT),
cytokeratin-19 (CK-19), cytokeratin-20 (CK-20), and carcinoembryonic
antigen (CEA) mRNA were used to detect CTCs in the
peripheral blood of 194 stage II CRC patients who underwent
potentially curative (R0) resection between January 2002 and December
2005. Digoxigenin (DIG)-labeled cDNA were amplified by
RT-PCR from the peripheral blood samples, which were then
hybridized to the membrane-array. All patients were followed up
regularly, and their outcomes were investigated completely.
Results: Overall, 53 of 194 (27.3%) stage II patients were detected
with the expression of all 4 mRNA markers using the membranearray
method. After a median follow up of 40 months, 56 of 194
(28.9%) developed recurrence/metastases postoperatively. Univariately,
postoperative relapse was significantly correlated with the
depth of invasion (P  0.001), the presence of vascular invasion (P 
0.001), the presence of perineural invasion (P  0.048), the expression
of all 4 mRNA markers (P  0.001), and the number of
examined lymph nodes (P  0.031). Meanwhile, using a multivariate
logistic regression analysis, T4 depth of tumor invasion (P 
0.013), the presence of vascular invasion (P  0.032), and the
expression of all 4 mRNA markers (P  0.001) were demonstrated
to be independent predictors for postoperative relapse. Combination
of the depth of tumor invasion, vascular invasion, and all 4 mRNA
markers as predictors of postoperative relapse showed that patients
with any 1 positive predictor had a hazard ratio of about
27-fold to develop postoperative relapse (P  0.001; 95% CI 
11.42– 64.40). The interval between the detection of all 4 positive
molecular markers and subsequently developed postoperative
relapse ranged from 4 to 10 months (median: 7 months). Furthermore,
the expression of all 4 mRNA markers in all stage II CRC
patients, or either stage II colon or rectal cancer patients were
strongly correlated with poorer relapse-free survival rates by
survival analyses (all P  0.001).
Conclusions: The pilot study suggests that the constructed membrane-
array method for the detection of CTCs is a potential auxiliary
tool to conventional clinicopathological variables for the prediction
of postoperative relapse in stage II CRC patients who have undergone
curative resection.

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