1.Genetic and Epigenetic Marker-Based DNA Test of Stool Is a Promising Approach for Colorectal Cancer Screening.
Sung Whan AN ; Nam Kyu KIM ; Hyun Cheol CHUNG
Yonsei Medical Journal 2009;50(3):331-334
Colorectal cancer (CRC) is one of the most common malignancies and leading cause of cancer-related deaths in the world. However, it may be treated effectively by surgical removal of the cancerous tissue if detected at early stages. Conventional tools for screening CRC are either invasive or inaccurate. Therefore, there is an urgent need to develop a reliable screening tools for CRC to significantly reduce its morbidity. In this regard, a novel DNA markers-based detection in stool is emerging as a promising approach.
Colorectal Neoplasms/*diagnosis/*genetics
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Epigenesis, Genetic/*genetics
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*Feces
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Genetic Markers/*genetics
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Tumor Markers, Biological/genetics
2.Expression of survivin and its splice variants in gastric cancer.
Zhengjiang, CHENG ; Lihua, HU ; Wenrong, FU ; Qin, ZHANG ; Xiaofeng, LIAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(4):393-8
Survivin variants specific real time quantitative RT-PCR was developed to analyze their expression in 53 paired cancer and para-cancerous tissues, and the expression of the wild-type survivin protein was detected by immunohistochemistry. The results showed that survivin mRNA and protein were expressed in gastric cancer and para-cancerous tissues. The survivin-2B was dominantly expressed in para-cancerous tissues, whereas the survivin-DeltaEx3 was more frequently detected in cancer tissues. The positive rate of survivin-2a was 100% in both cancer and para-cancerous tissues, but its relative transcript expression level was not significantly increased in cancer tissues in comparison with para-cancerous tissues. The correlation analysis revealed that the expression of survivin-2a mRNA was significantly associated with that of total survivin (r (s)=0.4178, P=0.0018), whereas inversely to that of survivin-DeltaEX3 (r (s)=-0.4506, P=0.0007). It was suggested that survivin-2a may act as an antagonist of survivin-DeltaEX3. The balance between antiapoptotic survivin iso-forms and nonantiapoptotic ones may play an important role in tumorigenesis and tumor progression. Promising value is hinted to analyze survivin and its variants in tumor early diagnosis and distinguishing malignant tumors from benign ones.
Microtubule-Associated Proteins/genetics
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Microtubule-Associated Proteins/*metabolism
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Protein Isoforms/genetics
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Protein Isoforms/metabolism
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RNA, Messenger/genetics
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RNA, Messenger/metabolism
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Stomach Neoplasms/*metabolism
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Stomach Neoplasms/pathology
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Tumor Cells, Cultured
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Tumor Markers, Biological/genetics
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Tumor Markers, Biological/*metabolism
4.Expression and prognostic significance of survivin in the progression of bladder transitional cell cancer.
Yanbo, WANG ; Zhaohui, ZHU ; Fuqing, ZENG ; Liang, WANG ; Yu, WU ; Wei, XIA ; Shi'an XING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(4):444-7
The expression of survivin, a member of inhibitor of apoptosis (IAP) family, was examined in bladder transitional cell cancer (BTCC) tissue and adjacent normal tissues to examine its clinical implication in the development of BTCC. Thirty specimens of bladder cancer were detected for the expression of survivin by using immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (RT-QPCR) in BTCC tissue and adjacent normal tissues. Our results showed that the positive rate of survivin immunostaining specimen were 0 and 60% (18/30) in the adjacent normal tissues, bladder cancer, respectively. The-DeltaDeltaCT value of survivin in bladder cancer tissue was 10.2829 (9.0034-11.5624) times that in the adjacent normal tissues. The expressions of survivin were correlated with the pathological grades of tumor and clinical stages. It is concluded that there was only weak expression of survivin mRNA in the adjacent normal tissues, but the expression of survivin mRNA in bladder cancer tissue was much higher than that in the adjacent normal tissues and the expression of survivin was correlated with pathological grades and clinical stages of tumor.
*Carcinoma, Transitional Cell/metabolism
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*Carcinoma, Transitional Cell/pathology
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Microtubule-Associated Proteins/genetics
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Microtubule-Associated Proteins/*metabolism
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Prognosis
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RNA, Messenger/genetics
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RNA, Messenger/metabolism
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Tumor Markers, Biological/genetics
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Tumor Markers, Biological/*metabolism
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Urinary Bladder Neoplasms/*metabolism
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Urinary Bladder Neoplasms/*pathology
5.Etiology and Carcinogenesis of Pancreatic Ductal Adenocarcinoma.
The Korean Journal of Gastroenterology 2008;51(2):71-83
Pancreatic cancer is currently the major leading cause of cancer-related deaths in the Western countries with an overall 5-year survival rate of less than 3. The key aim of investigation is to identify the cellular population in which some of the earliest molecular events occur, presumably the ultimate target for carcinogenic insult. Advances in pathological classification and genetics have improved our descriptive understanding of this disease. However, important aspects of pancreatic cancer biology remain poorly understood. Factors associated with the increased risk of pancreatic cancer include smoking, chronic pancreatitis, diabetes, prior gastric surgery, and exposure to radiation or chemicals. A number of syndromes have been identified with the increased incidence of pancreatic cancer, including familial atypical multiple-mole melanoma syndrome, hereditary nonpolyposis colorectal cancer, and hereditary pancreatitis, etc. Recently, there have been growing evidences that stem cell biology could provide new insights into the understanding of cancer biology. Three postulates regarding the relationship between stem and tumor cells have been proposed. First, the similarities in the mechanims that regulate self-renewal of normal stem cells and cancer cells. Second, the possibility that tumor cells might arise from normal stem cells and third, the notion that tumors might contain 'cancer stem cells' - rare cells with indefinite proliferative potential which drive the formation and growth of tumors. New insights for the cancer stem cells and their possible markers in pancreatic cancer have been suggested recently. Further observations of molecular and cellular events in the early stage of pancreatic carcinogenesis may have important implications regarding the cellular lineage responsible for pancreatic ductal metaplasia and neoplasia, and provide further support for the presence of stem cell capabilities within mature pancreatic epithelium.
Carcinoma, Pancreatic Ductal/*etiology/genetics/pathology
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Disease Progression
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Humans
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Mutation
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Neoplasm Proteins/genetics
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Neoplastic Syndromes, Hereditary/genetics
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Oncogenes
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Pancreatic Neoplasms/diagnosis/*etiology/genetics
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Risk Factors
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Tumor Markers, Biological
6.Gene Expression Profiling using Oligonucleotide Microarray in Atrophic Gastritis and Intestinal Metaplasia.
Kyong Rae KIM ; Soo Youn OH ; Ung Chae PARK ; Joon Ho WANG ; Jae Dong LEE ; Hyuk Jung KWEON ; Sang Yoon KIM ; Seung Hwa PARK ; Dong Kug CHOI ; Chan Gil KIM ; Seongc Ho CHOI
The Korean Journal of Gastroenterology 2007;49(4):209-224
BACKGROUND/AIMS: The atrophic gastritis with intestinal metaplasia of gastric mucosa has been considered to be the major factor of carcinogenesis in the stomach. However, the key molecules are still poorly understood. To elucidate the molecular genetic basis, we report the results of our initial microarray data to analyze the genome pattern in patients with atrophic gastritis and intestinal metaplasia of the stomach. METHODS: We used oligonucleotide microarray technique to evaluate the gene expression profiles in atrophic gastritis with intestinal metaplasia, in comparison with those of normal mucosa. For the identification of differentially expressed genes, Significance Analysis of Microarrays (SAM) package method was used. The results were analyzed using global normalization, intensity dependent normalization, and box plot normalization. RESULTS: Eight genes including FABP, REG, OR6C1, MEP1, SLC6A1, SI, Mucin 1, and RAB23 in mucosa of atrophic gastritis and intestinal metaplasia were up-regulated by more than 10 times as compared with normal gastric mucosa. Only one gene, LOC44119 was down-regulated by more than 10 times of the expression as compared with normal gastric mucosa. In respect to the expression of known genes related to gastric carcinogenesis, 8 genes including FN1, SRMS, TP53, TP53IMP2, TP53I3, FGFR4, TGFB1, and TGFA showed up- and down-regulations more than 2 folds in expression pattern. CONCLUSIONS: We could identify a total genome pattern in patient with atrophic gastritis and intestinal metaplasia using oligonucleotide microarray. We believe that the current results will serve as a fundamental bioinformative basis for clinical applications in diagnosis and treatment of gastric cancer and precancerous lesion in the future.
Down-Regulation
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Gastritis, Atrophic/*genetics/metabolism
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Gene Expression Profiling
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Humans
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Intestines/*metabolism/*pathology
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Metaplasia/genetics/metabolism
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Microarray Analysis
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Tumor Markers, Biological/genetics/metabolism
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Up-Regulation
7.Expression and implication of hypoxia inducible factor-1alpha in prostate neoplasm.
Ping, HAO ; Xiaochun, CHEN ; Huaizhen, GENG ; Longjie, GU ; Jiang, CHEN ; Gongcheng, LU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2004;24(6):593-5
To study the expression of hypoxia inducible factor-1alpha (HIF-1alpha) protein in prostate cancer (Pca) and its biological significance, the expression of HIF-1alpha was assayed by means of immunohistochemical technique in 42 prostate cancer, 12 prostatic intraepithelial neoplasm (PIN) and 9 normal prostate tissue (NP) specimens. Western blot was used to examine the expression of HIF-1alpha in prostate cancer cell line (PC-3M) induced by different oxygen tension. HIF-1alpha expression was positive in 33 Pca and 9 PIN specimens, and the positive rate of HIF-1alpha was higher in distant metastasis patients than in patients without metastasis of prostate cancer (P<0.05), while there was no expression of HIF-1alpha in NP. The level of HIF-1alpha in PC-3M significantly increased with the decrease of oxygen tension (P<0.01). Overexpression of HIF-1alpha is the preliminary event of the formation of Pca, which may induce carcinoma into malignant phenotype. Thus it may serve as an early diagnosis marker and the novel target for Pca treatment.
Adenocarcinoma/*metabolism
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Cell Line, Tumor
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Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics
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Prostatic Neoplasms/*metabolism
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Tumor Markers, Biological/*biosynthesis
8.Expression of Pin1 and Ki67 in cervical cancer and their significance.
Hongyu, LI ; Hongling, SHEN ; Qian, XU ; Dongrui, DENG ; Shixuan, WANG ; Yunping, LU ; Ding, MA
Journal of Huazhong University of Science and Technology (Medical Sciences) 2006;26(1):120-2
In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P < 0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P < 0.05). No significant difference in the Pin1 expression was found between disease stages (FIGO), pathological grades or pelvic lymph node metastasis status (P > 0.05). The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix (P < 0.05). In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P < 0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.
Cervical Intraepithelial Neoplasia/metabolism
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Ki-67 Antigen/*biosynthesis
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Ki-67 Antigen/genetics
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Peptidylprolyl Isomerase/*biosynthesis
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Peptidylprolyl Isomerase/genetics
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Tumor Markers, Biological
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Uterine Cervical Neoplasms/*metabolism
9.Identification of molecular markers for the oncogenic differentiation of hepatocellular carcinoma.
Gyung Ran YU ; Seong Hun KIM ; Seon Hwa PARK ; Xiang Dan CUI ; Dong Yuan XU ; Hee Chul YU ; Baik Hwan CHO ; Young Il YEOM ; Sang Soo KIM ; Sang Bae KIM ; In Sun CHU ; Dae Ghon KIM
Experimental & Molecular Medicine 2007;39(5):641-652
The aim of this study was to identify molecular markers associated with oncogenic differentiation in hepatocellular carcinoma (HCC). Using an unsupervised clustering method with a cDNA microarray, HCC (T) gene expression profiles and corresponding non-tumor tissues (NT) from 40 patients were analyzed. Of total 217 genes, 72 were expressed preferentially in HCC tissues. Among 186 differentially regulated genes, there were molecular chaperone and tumor suppressor gene clusters in the Edmondson grades I and II (GI/II) subclass compared with the liver cirrhosis (LC) subclass. The Edmondson grades III and IV (GIII/IV) subclass with a poor survival (P = 0.0133) contained 122 differentially regulated genes with a cluster containing various metastasis- and invasion-related genes compared with the GI/II subclass. Immunohistochemical analysis revealed that ANXA2, one of the 72 genes preferentially expressed in HCC, was over-expressed in the sinusoidal endothelium and in malignant hepatocytes in HCC. The genes identified in the HCC subclasses will be useful molecular markers for the genesis and progression of HCC. In addition, ANXA2 might be a novel marker for tumor angiogenesis in HCC.
Annexin A2/genetics
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Carcinoma, Hepatocellular/*genetics/pathology
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Gene Expression Profiling
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Genes, Tumor Suppressor
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Humans
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Liver Neoplasms/*genetics/pathology
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Molecular Chaperones/genetics
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Multigene Family
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Oligonucleotide Array Sequence Analysis
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Oncogenes
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Tumor Markers, Biological/*genetics
10.Clinical Significance of Aberrant Wnt7a Promoter Methylation in Human Non-Small Cell Lung Cancer in Koreans.
Tae Hyung KIM ; Ji Yong MOON ; Sang Heon KIM ; Seung Sam PAIK ; Ho Joo YOON ; Dong Ho SHIN ; Sung Soo PARK ; Jang Won SOHN
Journal of Korean Medical Science 2015;30(2):155-161
The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.
Cadherins/biosynthesis
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Carcinoma, Non-Small-Cell Lung/*genetics/mortality
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DNA Methylation/*genetics
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Female
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Humans
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Lung Neoplasms/*genetics/mortality
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Male
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Middle Aged
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Neoplasm Metastasis/genetics
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Neoplasm Staging
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Promoter Regions, Genetic/*genetics
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Republic of Korea
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Tumor Markers, Biological/genetics
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Wnt Proteins/*genetics