Association between gut-enriched Kruppel-like factor and prognosis of patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the expression of gut-enriched Kruppel-like factor 4(KLF4) in gastric cancer, and its association with prognosis.</p><p><b>METHODS</b>Surgical specimens were collected from 264 patients undergoing radical surgery between 2004 and 2009 in the Affiliated Qianfoshan Hospital, Shandong University. KLF4 mRNA level of specimens was detected by real-time PCR. KLF4 protein expression was measured by immunohistochemistry on tissue microarray, which contained primary gastric cancer, corresponding para-cancerous tissue, and paired lymph node metastases.</p><p><b>RESULTS</b>Real-time PCR revealed that mRNA level of KLF4 was down-regulated in gastric cancer compared with paired normal gastric mucosa. Immunohistochemistry on tissue microarray showed gastric cancer tissues had significantly lower KLF4 levels compared with paired normal gastric tissues. By univariate and multivariate analysis, KLF4 was a significant predictor of survival and recurrence.</p><p><b>CONCLUSION</b>KLF4 expression is significantly down-regulated in gastric cancer, and is an independent predictor of survival and recurrence.</p>

Screening of tumor suppressor genes on 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes (TSGs). However, the mechanism of colorectal cancer (CRC) is not completely understood, and many genes may be involved in the colorectal carcinogenesis. The purpose of this study was to screen for the potential TSGs on chromosome 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer, to explore whether colorectal cancer in the Chinese population has unique genetic alterations and determine whether other putative TSGs exist and contribute to colon carcinogenesis.</p><p><b>METHODS</b>Six polymorphic microsatellite markers, at a density of approximately one marker in every 1.6 cM, were chosen for refined loss of heterozygosity (LOH) mapping of 1q31.1-32.1. Eighty-three colorectal cancer patients' tumor and normal DNA were analyzed via polymerase chain reaction (PCR) for these microsatellite markers. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. On the basis of refined LOH mapping results, we undertook a microarray-based expression screening to identify tumor association genes in 19 of the CRC cases.</p><p><b>RESULTS</b>The average LOH frequency of 1q31.1-32.1 was 24.41%, with the highest frequency of 36.73% (18/49) at D1S2622, and the lowest of 16.42% (11/67) at D1S412. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622. There was no significant association between LOH of any marker in the studied regions and the clinicopathological data (patient sex, age, tumor size, growth pattern, or Dukes stage). On the basis of refined mapping results, we chose 25 genes located in the D1S413-D1S2622 (1q31.3-32.1) region and presented a microarray-based high throughput screening approach in 19 sporadic CRC cases to identify candidate CRC related tumor suppressor genes. This study found 4 significantly down-expressed genes, including CSRP1, LMOD1, PPP1R12B and CFHL3. There was no significant association between expression levels of CFHL3, CSRP1, LMOD1, PPP1R12B and the clinicopathological data. By database searching, CSRP1 was hypothesized to be a colorectal cancer related tumor suppressor gene.</p><p><b>CONCLUSIONS</b>Through detailed deletion mapping, we found that the 1q31.3-32.1 region might harbor one or more colorectal cancer related tumor suppressor gene (s). And by microarray-based high-throughput screening of candidate genes located in this region and by subsequent database searching, we present the first evidence that CSRP1 might be involved in the progression of CRC.</p>

Refined deletion mapping of loss of heterozygosity on 22q13 in sporadic colorectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To screen the candidate TSGs on 22q13 involved in sporadic colorectal cancer.</p><p><b>METHODS</b>The DNA samples of 83 cases with colorectal carcinoma and normal tissues were analyzed using eight fluorescent labeled polymorphic microsatellite markers by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software was used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by chia2 test.</p><p><b>RESULTS</b>The prevalence of LOH was 35.58%, and the average hereditary distance was 1.9 cM. The highest frequency of LOH (D22S1160 locus) and the lowest (D22S1170 locus) were 64.71% and 20%, respectively. Two obvious LOH regions were detected: One between D22S1171 locus and D22S274 locus (about 2.7 cM); another between D22S1160 and D22S1149 locus (about 1.8 cM). Furthermore,significant differences were observed between the frequency of LOH on D22S1171 locus and tumors location (P=0.020), the frequency of LOH on D22S114 locus and liver metastasis (P=0.008), the frequency of LOH on D22S1160 locus and lymph node metastasis (P=0.016). No significant differences were found between LOH on other loci and those factors above. Gene function screening revealed that ARHGAP8 and PPARA gene were involved in carcinogenesis.</p><p><b>CONCLUSIONS</b>Two obvious high frequency LOH regions are detected by refined deletion mapping. One locates between D22S1171 locus and D22S274 locus (about 2.7 cM); another locates between D22S1160 and D22S1149 locus (about 1.8cM), ARHGAP8 and PPARA gene may be TSGs which contribute to carcinogenesis and progression of sporadic CRC on 22q13 region.</p>