AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed...AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using x2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables.RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P＜0.05). Moreover, higher vWF plasmalevels were associated with advanced tumor stage (P＜0.05) and the presence of multiple metastases (P = 0.014).Patients with lower vWF plasma levels (≤ 160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis,plasma vWF levels (P＜0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014)were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.展开更多
AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found wi...AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear.METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status.RESULTS: The average copy numbers (±SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3:4.19 (±0.69); CCNL1:5.24 (±0.67); SvC4L1: 2.01 (±0.16); EVI1: 2.02 (±0.12);hTERC: 5.28 (±0.54); SKIL: 2.71 (±0.14); EIF5A2: 1.95(±0.12); ECT2:9.18 (±1.68); PIK3CA: 8.13 (±1.17);EIF4G1:1.07 (±0.05); SST: 3.07 (±0.25); TP63: 2.51(±0.22); TFRC: 2.42 (±0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC andSKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and SST, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis.CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes(SSR3, SMC4L1, ECT2, and SST) were identified. TP63is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.展开更多
基金Supported by a Grant From the Yen Tjing-Ling Medical Foundation
文摘AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using x2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables.RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P＜0.05). Moreover, higher vWF plasmalevels were associated with advanced tumor stage (P＜0.05) and the presence of multiple metastases (P = 0.014).Patients with lower vWF plasma levels (≤ 160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis,plasma vWF levels (P＜0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014)were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.
基金Supported by the National Microarray and Gene Expression Analysis Core Facility of the National Research Program for Genomic Medicine at National Yang-Ming University (http://www.ym.edu. tw/microarray),annual project Grant From National Science Council (Grant NO. NSC 92-2314-B-075-055), Taiwan, China
文摘AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear.METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status.RESULTS: The average copy numbers (±SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3:4.19 (±0.69); CCNL1:5.24 (±0.67); SvC4L1: 2.01 (±0.16); EVI1: 2.02 (±0.12);hTERC: 5.28 (±0.54); SKIL: 2.71 (±0.14); EIF5A2: 1.95(±0.12); ECT2:9.18 (±1.68); PIK3CA: 8.13 (±1.17);EIF4G1:1.07 (±0.05); SST: 3.07 (±0.25); TP63: 2.51(±0.22); TFRC: 2.42 (±0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC andSKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and SST, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis.CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes(SSR3, SMC4L1, ECT2, and SST) were identified. TP63is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.
