Purpose and Experimental Design: To identify cancer-related genes, the expression profiles of colorectal cancer cells and normal epithelial cells were examined and compared using laser microdissection and cDNA microarray analysis. From these combined techniques, several cancer-related genes, including TROP2 , were identified. TROP2 is known as a calcium signal transducer and is highly expressed in several types of tumors. However, no studies have investigated the significance of TROP2 expression in colorectal cancer. Thus, the expression status of TROP2 was investigated in 74 colorectal cancer samples by quantitative real-time reverse transcription-PCR and immunohistochemical studies. Results: Laser microdissection and cDNA microarray analysis showed that there were 84 overexpressed genes in cancer cells. One of the highly overexpressed genes wasTROP2. Quantitative real-time reverse transcription-PCR showed that TROP2 expression in cancer samples was significantly higher than in normal samples (P < 0.001). The samples were divided into high (n = 26) and low (n = 48) TROP2 expression groups. The cases with high TROP2 expression showed a higher frequency of liver metastasis (P = 0.005) and more cancer-related death (P = 0.046). Those cases also had an inclination of deeper depth of invasion (P = 0.064) and more lymph node metastasis (P = 0.125). Interestingly, the patients with high TROP2 expression tumors had poorer prognosis (P = 0.0036). Multivariate analysis showed that TROP2 expression status was an independent prognostic factor (relative risk, 2.38; 95% confidence interval, 1.29-4.74; P < 0.01).Conclusion: TROP2 is one of the cancer-related genes that correlates with biological aggressiveness and poor prognosis of colorectal cancer. Thus,TROP2 is a possible candidate gene for diagnosis and molecular target therapy of colorectal cancer.Colorectal cancer is one of the most prevalent cancers in the world. In Japan, the disease rate of colorectal cancer patients has doubled over the past 20 years, with f75 of 100,000 people suffering from the disease today. Additionally, colorectal cancer has been the second cause of death in neoplastic disease (1). Recently, molecular target therapy and cancer immunotherapy for solid cancers have been introduced to the clinic (2 -5). However, indications for these therapies are limited due to the low frequency of target gene expression, unstable effectiveness, and/or severe side effects (5, 6). Thus, there is a pressing need to explore novel cancer-specific genes to serve as molecular targets for therapy and cancer specific immunotherapy.In this study, the gene expression profiles were compared between cancer cells and normal epithelial cells using the combined techniques of laser microdissection and cDNA microarray analysis to explore cancer-related or cancer-specific genes. From this analysis, several cancer-related genes were identified. Among them, TROP2 showed markedly different expression between cancer cells and normal epithelial cells.Fornaro et al. cloned the ...

TRIM29 expression may serve as a good marker of lymph node metastasis in gastric cancer.

Purpose: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer. Experimental Design: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles. Results: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P < 0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P < 0.01), more often in the left colon (P < 0.05), and had shallower invasion into the bowel wall (P < 0.05) compared with those with low expression. There was no significant difference between high-and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P < 0.05), more dominant proliferation (P < 0.001), and less apoptosis than mock cells. Conclusions:The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.

Advanced technology in molecular biology has provided us powerful tools for the diagnosis and treatment for cancer. We herein adopted a new methodology to identify a novel cancer/ testis (CT) antigen with high frequency of expression in colorectal cancer as follows: (a) combining laser microdissection and cDNA microarray was used to analyze the gene expression profile of colorectal cancer cells; (b) genes overexpressed in testis and underexpressed in normal colon epithelium were analyzed using cDNA microarray; and (c) the gene expression profile of colorectal cancer cells was compared with that of normal testis. Using this methodology, we selected 38 candidates for CT antigen. Among these genes, we identified a novel CT antigen, serine/threonine kinase 31 (STK31), which was previously reported as a gene expressed in spermatogonia. Reverse transcription-PCR analysis showed that STK31 gene expression levels in cancer samples were significantly higher (P < 0.0001) than those in normal samples. The STK31 gene was frequently expressed not only in colorectal cancer but also in gastric and esophageal cancer. Moreover, STK31 peptide was able to elicit specific CTLs and induced CTLs lysed either peptide-loading or endogenously STK31-expressing target cells. These results showed that the new methodology in this study facilitated identification of CT antigens and that STK31 may be a candidate for cancer immunotherapy against gastrointestinal cancer. [Cancer Res 2008;68(4):1074-82]

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-ß superfamily and bone morphogenetic protein (BMP) subfamily, plays a role in regulation of development and differentiation. Although some members of BMP subfamily have been reported to correlate with cancer, the significance of GDF11 has not been studied in a clinical oncology setting. The current study explored the clinicopathological significance of GDF11 expression in colorectal cancer. Quantitative real-time reverse transcription-PCR in colorectal cancer specimens obtained from 130 patients showed that GDF11 mRNA expression in cancer tissue was significantly higher than in normal tissue (p=0.001). Tumors were classified as high GDF11 expression (n=65) or low GDF11 expression (n=65). Patients whose tumors had high GDF11 expression showed a high frequency of lymph node metastasis (p=0.049) and had more cancerrelated deaths (p=0.040). Furthermore, the patients with high GDF11 expression had significantly poorer overall survival than those with low expression (p=0.0334). Although multivariate analysis showed that GDF11 was not an independent prognostic factor, these findings suggest that GDF11 may be a novel diagnostic and prognostic biomarker in patients with colorectal cancer.

A 30-year old man with cerebral palsy visited a local clinic complaining of abdominal distention, and was medicated. However, his abdominal symptoms did not improve, and he visited our hospital. Physical examination showed obvious abdominal distention with peritoneal signs in the lower abdomen. Abdominal computed tomography (CT) revealed the whirl sign like appearance of the intestinal mesentery, ascites in the Douglas pouch, and the distended small bowel in the pelvic space. He was thus diagnosed as torsion of the bowel with strangulation, and underwent emergency laparotomy. Intraoperatively, ileocecal portion was rotated counterclockwise by 360 degree. The rotated bowel was strangulated with extensive ischemic changes. Therefore, the discolored bowel was resected and was anastomosed. His postoperative course was uneventful and oral intake was started on postoperative day 3. He was discharged 20 days after surgery and remains well. The cecal volvulus often occurs in patients with cerebral palsy and senior persons, and their physical examination may not be pathognomonic, for which early establishment of definite diagnosis and urgent operation are important.

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