Qiong Huang

Zhejiang University, Hangzhou, Zhejiang Sheng, China

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Publications (38)83.18 Total impact

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    ABSTRACT: Regenerating islet-deprived gene family, number 4 (REG4), is a novel marker for intestinal differentiation. We performed immunohistochemical studies on REG4, cytokeratin (CK)7, CK20, and caudal type homeobox 2 (CDX2) in 291 ovarian mucinous tumors. There were 226 primary tumors and 65 metastatic tumors. The primary tumors comprised 69/226 mucinous cystadenomas, 79/226 mucinous borderline tumors (64/79 intestinal-type and 15/79 endocervical-like tumors), and 78/226 mucinous carcinomas. We found that REG4 expression was significantly higher in mucinous borderline tumors (30/79, 38.0%) and primary mucinous carcinomas (26/78, 33.3%) than in mucinous cystadenomas (4/69, 5.8%; P<0.05). However, REG4 expression was more commonly associated with intestinal-type, borderline, mucinous tumors rather than the endocervical-like type (30/64 vs. 0/15, P<0.001). There was a significant correlation between the REG4 and CDX2 expression profiles in primary ovarian mucinous tumors (r=0.772, P<0.001). REG4, CDX2, and diffuse CK20 had higher expression frequencies in metastatic lower gastrointestinal adenocarcinoma than in primary mucinous tumors (P<0.01). The CK7/REG4 coordinate expression profile was comparable in diagnostic value to CK7/CK20 or CK7/CDX2 profile. We conclude that REG4 expression is common in mucinous borderline tumors of the intestinal type as it is absent in the endocervical-like form in this series. Expression of CK7/REG4 may contribute to the differential diagnosis between primary and metastatic ovarian mucinous tumors.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 08/2013; · 1.63 Impact Factor
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    ABSTRACT: Lymph node metastasis is the major concern that causes death in colorectal cancers. However, biomarkers for cancer metastasis are still lacking. In this study, we applied an LC-MS/MS-based label-free quantitative proteomics approach to compare the differential secretome of a primary cell line SW480 and its lymph node metastatic cell line SW620 from the same colorectal cancer patient. We identified a total of 910 proteins from the conditioned media and 145 differential proteins between SW480 and SW620 (>1.5-fold change). The differential expression pattern of 6 candidate proteins was validated by Western blot analysis. Among them, trefoil factor 3 and growth/differentiation factor 15, two up-regulated proteins in SW620, were further analyzed in a large cohort of clinical tissue and serum samples. Sandwich ELISA assay showed that the serum levels of both proteins were significantly higher in lymph node metastatic colorectal cancers. Receiver operating characteristic curve analysis confirmed that serum trefoil factor 3 and growth/differentiation factor 15 could provide a discriminatory diagnostic test for predicting colorectal cancer metastasis. Immunohistochemical analysis also showed that the overexpression of trefoil factor 3 or growth/differentiation factor 15 in colorectal cancer was associated with lymph node metastatic behavior. This study showed an accurate, sensitive, and robust label-free quantitation approach for differential analysis of cancer secretome. The comparison of the cancer secretome in vitro is a feasible strategy to obtain valuable biomarkers for potential clinical application. Both trefoil factor 3 and growth/differentiation factor 15 could serve as potential biomarkers for the prediction of colorectal cancer metastasis.
    Journal of Proteome Research 11/2009; 9(1):545-55. · 5.06 Impact Factor
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    ABSTRACT: CDX2 has been shown to play an important role in the pathogenesis of colorectal cancer. The aim of this study was to investigate whether genetic variants in CDX2 contributed to the development and progression of colorectal cancer in a Chinese population. We detected the polymorphisms in the CDX2 coding regions in 126 patients with colorectal cancer and matched tumor-free subjects by PCR-based DHPLC. The correlation between the genotypes and clinicopathological parameters among colorectal cancer cases was also investigated. Three SNPs were identified in the coding region of the CDX2 gene. Neither the genotype frequencies nor allele frequencies of CDX2 polymorphisms showed significant difference from those in healthy controls. There were also no significant association between genotypes and clinicopathological features. When we examined the linkage disequilibrium between three SNPs using expectation-maximization algorithm, we found that there is strong linkage disequilibrium among these SNPs, but no significant difference was found in haplotypes distribution. Our present data suggest that the CDX2 polymorphisms may not be used as a useful marker to predicate susceptibility of colorectal cancer in Chinese.
    Molecular and Cellular Biochemistry 06/2009; 331(1-2):27-30. · 2.33 Impact Factor
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    ABSTRACT: The insulin-like growth factor binding protein 7 (IGFBP7) gene is regulated by DNA methylation in colon cancer, which was identified in our previous study. In this study, we examined the effects of DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) on IGFBP7 reactivation and cell biological behaviors in vitro to investigate a potential role for 5-aza-dC in treating colorectal cancer. 5-aza-dC treatment showed induction of IGFBP7 transcription in these cancer cells. It consequently led to inhibition of cell growth, cell cycle arrest and apoptosis, suppression of cell migration and invasion in colon cancer cell lines. We examined the effects of 5-aza-dC on reexpression of previously silenced IGFBP7 and its global effects on cell cycle, apoptosis, migration and invasion in three colon cancer cell lines, SW620, HT29 and COLO205. Our findings indicate that 5-aza-dC may have anticancer function for colon cancer and restoration of IGFBP7 may involve in the biological effects induced by 5-aza-dC in colon cancer cell lines. These data suggest that 5-aza-dC has clinical potential in the treatment of colorectal cancer.
    Cancer biology & therapy 01/2009; 7(12):1896-900. · 3.29 Impact Factor
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    ABSTRACT: Our purpose was to investigate the role of SOX9, a novel downstream molecule of beta-catenin, in colorectal cancer. Expression of SOX9 and beta-catenin was detected by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction (Q-PCR), and Western blot in colorectal cancer. The correlation between SOX9 or beta-catenin expression and clinicopathologic parameters was also analyzed. Immunostaining, Q-PCR, and Western blot consistently confirmed SOX9 up-regulation in colorectal cancer compared with normal mucosa (P < .05). Immunostaining showed more SOX9+ cells in the lower zone of colonic crypts than in the upper zone (P < .05). Cancers with strong SOX9 immunostaining were significantly associated with a lower 5-year overall survival (40% [17/43] vs low expression, 69% [66/95]; P < .01). The Cox proportional hazards model showed that strong SOX9 expression was an independent adverse prognosticator in colorectal cancer (P < .05). The detection of SOX9 expression might contribute to predicting clinical outcomes for patients with colorectal cancer.
    American Journal of Clinical Pathology 12/2008; 130(6):897-904. · 2.88 Impact Factor
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    ABSTRACT: To investigate the methylation status of 5'CpG island of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) in colorectal cancer and its relationship with gene expression and clinicopathologic parameters. Semi-quantitative reverse transcription-PCR (RT-PCR) was used to detect the expression of IGFBP-rP1 in 46 cases of colorectal cancer and their matched normal mucosa. Methylation-specific PCR (MSP) was applied to evaluate the methylation status of 5'CpG island of IGFBP-rP1. Colon cancer cell lines LoVo and SW620 were treated with demethylation agent 5-aza-2'-deoxycytidine (5-aza-dC), followed by RT-PCR and MSP detection. At the mRNA level, the expression of IGFBP-rP1 was higher in colorectal cancer tissue than that in the matched normal mucosa (P < 0.05). IGFBP-rP1 was methylated in 28/46 (60.9%) cases of colorectal cancer and 37/46 (80.4%) matched normal mucosa samples (P < 0.05). A negative correlation was found between IGFBP-rP1 expression and its methylation status. The expression of IGFBP-rP1 was restored in LoVo and SW620 after treatment with 5-aza-dC and MSP confirmation of its demethylation status. No relationships was found between the methylation status and clinicopathologic parameters. IGFBP-rP1 expression is negatively correlated with its methylation status in colorectal cancer. DNA methylation is one of the mechanisms regulating the expression of IGFBP-rP1. Hypomethylation of IGFBP-rP1 gene with its overexpression plays an important role in the initiation and development of colorectal cancer.
    Zhonghua bing li xue za zhi Chinese journal of pathology 09/2008; 37(8):512-6.
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    ABSTRACT: To explore the clinical significance of Krüppel-like factors 4 (KLF4) expression in colorectal cancer initiation and progression. We used quantitative real-time PCR to detect KLF4 mRNA expression in 49 colorectal cancer samples with individual-matched normal mucosa and eight concurrent adenomas. We also analysed the immunostaining pattern of KLF4 in additional 129 colorectal cancers and 48 sporadic colorectal adenomas with matched normal mucosa and correlated KLF4 staining with clinicopathological parameters and prognosis. KLF4 expression change was detected in SW480, SW620 and RKO cell lines after treatment of 5-aza-dC (10 microM) or butyrate sodium (4 mM). The large clinicopathological survey with combined methods confirmed a dynamic downregulation of KLF4 in individual-matched normal mucosa, adenoma and cancer (P < 0.05). The quantitative analysis of immunostaining pattern showed that KLF4 staining cells were more frequently seen in the upper zones than that in the lower zones of both normal mucosa and adenoma (P < 0.05). Survival analysis implied a trend toward better overall survival in KLF4-positive colorectal cancer patients with lymph node metastasis than that in KLF4-negative cancer with lymph node metastasis. In vitro study found elevated KLF4 mRNA expression in SW620 and RKO cells with 5-aza-dC treatment, implicating the underlying aberrant epigenetic modifications in regulating KLF4 expression at least in a subset of colorectal cancers. KLF4 is associated with terminal differentiation in colorectal epithelium and drastically downregulated in colorectal adenomas and cancers via possible epigenetic modifications. Loss of KLF4 protein expression might contribute to assessing prognosis in colorectal cancer with lymph node metastasis.
    Journal of Cancer Research and Clinical Oncology 08/2008; 134(8):891-8. · 2.91 Impact Factor
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    ABSTRACT: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor suppressor gene. This study attempted to explore a potential senescence-like role for IGFBP-rP1 in suppressing human colorectal cancer. Recombinant IGFBP-rP1 inhibited cell proliferation and induced G1 cell cycle arrest in RKO and CW2 cells. It induced a senescence-like phenotype by showing 2-fold higher beta-galactosidase activity in IGFBP-rP1-transfectants over that in control cells. Western blot confirmed down-regulation of phosphorylated retinoblastoma protein (pRB) and up-regulation of p53 in IGFBP-rP1-transfectants as compared with control cells. Thus, IGFBP-rP1 might be a key molecule in the cellular senescence pathway. Our results uncovered a novel molecular mechanism involving the altered expression of pRB and p53 for tumor suppressor gene IGFBP-rP1 in colorectal cancer. Restoration of IGFBP-rP1 function might have potential therapeutic significance in colorectal cancer.
    Experimental and Molecular Pathology 06/2008; 85(2):141-5. · 2.13 Impact Factor
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    ABSTRACT: Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in cancer initiation, invasion, and metastasis. The aim of this study was to investigate whether common genetic variants in these two key MMPs are associated with the development and progression of colorectal cancer in a Chinese population. We detected the MMP-2-790T/G, -955A/C, -1575G/A, and MMP-9-1562 C/T polymorphisms in 126 colorectal cancer patients and matched normal controls by PCR-denaturing high-performance liquid chromatography (DHPLC) or PCR-restriction fragment length polymorphism (RFLP), respectively. We found that the G/G genotype in the MMP-2-1575G/A polymorphism was significantly increased in colorectal cancer patients than in the controls (odds ratio (OR), 1.96; 95% CI, 1.06-3.64). Colorectal cancers with G/G genotype were more common with serosa/adventitia layer involvement than those with G/A+A/A genotypes (P<0.05). However, no significant differences were observed in distribution of the MMP-2-790T/G, -955A/C, and MMP-9-1562 C/T polymorphisms or haplotype of MMP-2 SNPs between patients and controls. Our results suggest that the presence of -1575G allele in the MMP-2 promoter region may be of significance in the assessment of colorectal cancer risk and invasive potential.
    Molecular Carcinogenesis 12/2007; 46(11):924-9. · 4.27 Impact Factor
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    ABSTRACT: Adenoma is the major precursor lesion of colorectal cancer, one of the most common cancers worldwide. The elucidation of the molecular mechanism underlying adenoma is essential for early detection, prevention, and intervention of colorectal cancer. Using a combination of two-dimensional gel electrophoresis and mass spectrometry, we identified 27 differentially expressed proteins in adenoma, compared with matched normal mucosa and cancer tissue. Seventeen proteins were upregulated and six downregulated in adenoma when compared with the same proteins in individual-matched normal mucosa. Four were downregulated, but none upregulated in adenoma when compared with the same proteins in matched cancer tissue. Two novel proteins, mimecan and thioredoxin domain-containing protein 5 (TXNDC5), were further validated by Western blot in 8 colorectal adenomas and 19 cancers that were matched with normal mucosa. All adenoma and cancer tissues did not express mimecan, but all normal mucosa did (P < 0.01). In contrast, TXNDC5 was significantly upregulated in colorectal adenoma and cancer tissues as compared with that in normal mucosa (P < 0.05). This study clearly demonstrated that absence of mimecan and upregulation of TXNDC5 are involved in the early development of colorectal cancer. Thus, the differentially expressed proteins might serve as potential biomarkers for colorectal cancer detection and intervention.
    Experimental Biology and Medicine 11/2007; 232(9):1152-9. · 2.80 Impact Factor
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    ABSTRACT: Classification based on a combination of molecular and pathologic predictors had never been done using hierarchical cluster analysis. For this purpose, we identified prognostic classification based on molecular predictors, pathologic and molecular predictors, and compared their respective prognostic efficacy together with that of tumor-node-metastasis (TNM) stage. Moreover, we investigated the prognostic significance of molecular classification in different TNM stage. Six pathologic predictors (p) and 13 immunohistochemical predictors (m) were investigated in 221 colorectal carcinomas. Unsupervised hierarchical clustering analysis was done to group the data. Survival analysis was done by Kaplan-Meier method and log-rank test, and by multivariate COX proportional hazard model. Six pathologic predictors and four molecular predictors were of significant prognostic value (P <or= 0.05). One molecular predictor showed a trend toward significance (P = 0.085). Hierarchical clustering analysis was done based on different combinations (5p, 13m, 5m, 5p13m, and 5p5m), and distinct groups were produced except 5p (the TNM stage was excluded). Groups identified by 5m (P = 0.053) and 5p5m (P = 0.000) showed significant differences in prognosis. Groups identified by 5p5m and TNM stage were confirmed as the independent prognostic factors in a multivariate COX proportional hazard model. Moreover, groups identified by 5m could predict different prognoses in patients with stage II disease. Classification based on pathologic and immunohistochemical predictors is superior to that based only on molecular predictors on prognosis. Classification based on 5m could identify additional different prognoses in patients with stage II disease.
    Clinical Cancer Research 09/2007; 13(17):5082-8. · 7.84 Impact Factor
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    ABSTRACT: DNA methylation plays an important role during colorectal cancer (CRC) carcinogenesis. DNA methyltransferase 1 (DNMT1) is responsible for maintaining DNA methylation. We addressed the significance of DNMT1 expression in CRC. We measured the expression of DNMT1 in CRC tissues and in their corresponding distal normal colorectal mucosa using reverse transcriptase-polymerase chain reaction and immunohistochemical analysis. The mean +/- SD of DNMT1 mRNA in CRC tissues was 1.04 +/- 0.36, which was significantly higher than that in their corresponding distal normal colorectal mucosa (0.58 +/- 0.44, P < 0.05). Fifty-eight out of 77 (75.3%) CRC tissues and only 30 out of 77 (39%) corresponding distant normal colorectal mucosa showed immunoreactivity (P < 0.001). We also found that the immunoreactivity of DNMT1 was higher in mucosa adjacent to cancer than in corresponding normal colorectal mucosa; high immunoreactivity was significantly correlated with poor differentiation in CRC tissues (P = 0.008). No significant associations were found between DNMT1 immunoreactivity and the following variables: age, sex, locations of cancer, Duke's phase, and the presence of lymph-node metastasis. These findings suggested that DNMT1 was associated with the malignant phenotype, and dysregulation of DNMT1 expression was present in tumor cells of CRC.
    International Journal of Colorectal Disease 07/2007; 22(6):661-6. · 2.24 Impact Factor
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    ABSTRACT: Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formation activity and induce apoptosis in RKO and SW620 cells. Correlation analysis between the expression of IGFBP7 in CRC tissue and the prognosis in 218 patients showed that high expression of IGFBP7 was associated with favorable prognosis. Based on above results, we conclude that IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis.
    Cancer biology & therapy 04/2007; 6(3):354-9. · 3.29 Impact Factor
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    ABSTRACT: To identify the differentially expressed proteins or peptides and potential biomarkers of tumorigenesis for colorectal cancers. Immobilized pH gradient two-dimensional gel electrophoresis (2-DE) was used to separate and obtain the differentially expressed protein spots between colorectal cancers and matched normal mucosa. Liquid chromatography/mass spectrometry (LC-MS/MS) was used to characterize these proteins. Selected candidate proteins were further studied by Western blot, semi-quantitative RT-PCR and immunohistochemical staining. Thirty-five protein spots showed marked expression changes (more than 5-fold) in colorectal carcinoma compared to normal mucosa. Fifteen proteins were up regulated and 20 were down regulated. Fourteen of these proteins were identified by tandem mass spectrometry, among which secretagogin (SCGN) was down-regulated and glucose-related protein (GRP) 78 was up-regulated in the tumors. The SCGN down-regulation was further supported by Western blot and RT-PCR analyses. Immunohistochemistry revealed that SCGN was strongly expressed in neuroendocrine cells of the colonic crypts and 53 of 54 (98%) neuroendocrine tumors. At protein level, although GRP78 was up regulated in colorectal carcinoma, there was no difference in the mRNA expression level between the tumor and paired normal mucosa. The 2-DE combined with MS is a powerful tool for screening potential tumor biomarkers. The differentially expressed candidate proteins identified by 2-DE may be of significance in understanding the tumorigenesis of the colon cancer. SCGN is a potential biomarker for neuroendocrinal differentiation. GRP78 up-regulation in colorectal carcinomas may be related to its post-translational modification.
    Zhonghua bing li xue za zhi Chinese journal of pathology 03/2007; 36(2):107-12.
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    ABSTRACT: Background and aim DNA methylation plays an important role during colorectal cancer (CRC) carcinogenesis. DNA methyltransferase 1 (DNMT1) is responsible for maintain-ing DNA methylation. We addressed the significance of DNMT1 expression in CRC. Materials and methods We measured the expression of DNMT1 in CRC tissues and in their corresponding distal normal colorectal mucosa using reverse transcriptase-poly-merase chain reaction and immunohistochemical analysis. Results The mean±SD of DNMT1 mRNA in CRC tissues was 1.04±0.36, which was significantly higher than that in their corresponding distal normal colorectal mucosa (0.58± 0.44, P<0.05). Fifty-eight out of 77 (75.3%) CRC tissues and only 30 out of 77 (39%) corresponding distant normal colorectal mucosa showed immunoreactivity (P<0.001). We also found that the immunoreactivity of DNMT1 was higher in mucosa adjacent to cancer than in corresponding normal colorectal mucosa; high immunoreactivity was significantly correlated with poor differentiation in CRC tissues (P=0.008). No significant associations were found between DNMT1 immunoreactivity and the following variables: age, sex, locations of cancer, Duke's phase, and the presence of lymph-node metastasis. Conclusion These findings suggested that DNMT1 was associated with the malignant phenotype, and dysregulation of DNMT1 expression was present in tumor cells of CRC.
    International Journal of Colorectal Disease 01/2007; 22(6). · 2.24 Impact Factor
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    ABSTRACT: Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.
    Journal of Zhejiang University SCIENCE B 12/2006; 7(11):929-32. · 1.11 Impact Factor
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    ABSTRACT: Preliminary data suggest that secretagogin (SCGN), a calcium-binding protein identified from our previous proteomics study of colorectal cancers, is a potentially useful neuroendocrine marker. In this study, we further analyzed SCGN expression in normal and tumor tissues from various organ sites compared with three other conventional neuroendocrine markers [chromogranin A (CgA), neuron specific enolase, and synaptophysin]. We found strong SCGN staining in most normal neuroendocrine tissues except in the adrenal cortex. SCGN expression was identified in 140 out of 213 neuroendocrine tumors and 12 conventional carcinomas with neuroendocrine differentiation. In a subset of neuroendocrine tumors, such as gastric neuroendocrine cancers and typical carcinoid tumors of rectum and ovary, SCGN showed strong staining while CgA expression was often negative. It is intriguing to note that SCGN staining was positive in 26 out of 31 small cell lung cancers, more frequently than the other three markers. We conclude that SCGN is a novel neuroendocrine marker that may be useful in routine surgical pathology practice.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2006; 449(4):402-9. · 2.68 Impact Factor
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    ABSTRACT: Matrix metalloproteinase-1 and matrix metalloproteinase-3 are implicated in all steps of cancer initiation, invasion, and metastasis. Recently, several genetic studies have demonstrated that matrix metalloproteinase-1-1607 ins/delG (1G/2G) polymorphism and matrix metalloproteinase-3-1612 ins/delA (5A/6A) polymorphism modify each transcriptional activity in allele-specific manners. In this study, we investigated whether these functional polymorphisms are associated with colorectal cancer in a Chinese population. Matrix metalloproteinase-1 and matrix metalloproteinase-3 genotypings were performed on 126 pathologically diagnosed colorectal cancer patients and 126 age-matched and gender-matched controls by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis or restriction fragment length polymorphism, respectively. The distributions of the matrix metalloproteinase-1 and matrix metalloproteinase-3 genotypes in healthy control subjects were inconsistent with Hardy-Weinberg equilibrium. Neither the genotype frequencies nor allele frequencies of matrix metalloproteinase-1 and matrix metalloproteinase-3 polymorphisms showed significant difference from those in healthy control subjects. There also were no significant associations between matrix metalloproteinase-1 and matrix metalloproteinase-3 genotypes and clinicopathologic features. When we examined the linkage disequilibrium between these two single nucleotide polymorphisms using expectation-maximization algorithm, we found that the two single nucleotide polymorphisms were in a strong linkage disequilibrium, but no significant difference was found in haplotype distribution. Our present data suggest that the matrix metalloproteinase-1 and matrix metalloproteinase-3 promoter polymorphisms may not be useful markers to predicate susceptibility of colorectal cancer in Chinese.
    Diseases of the Colon & Rectum 10/2006; 49(9):1439-44. · 3.34 Impact Factor
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    ABSTRACT: To identify proteins with colorectal cancer-specific regulation, comparative 2-DE of individual-matched normal and neoplastic colorectal tissue specimens was performed. We found 15 protein spots with concordantly increased and 20 protein spots with concordantly decreased intensity in tumor tissue (expression regulation more than fivefold). Nine of these proteins were identified by MS/MS. Interestingly, one of the proteins, which exhibited a marked down-regulation in colorectal cancer tissues, was the recently identified endocrine cell-expressed protein secretagogin. The reduction of the secretagogin content in colorectal cancer tissues was confirmed by comparative immunoblotting (n = 17) and RT-PCR (n = 22) as well as by immunohistochemistry (n = 45) of individual-matched neoplastic and normal colorectal tissue specimens. Immunohistochemistry revealed absence of secretagogin-expressing cells in most of the colorectal cancer tissue specimens. However, some colorectal cancers were characterized by secretagogin-expressing cells. In normal mucosa, positively stained cells exhibited a neuroendocrine cell-characteristic morphology and mucosal location. In colorectal cancer tissues, secretagogin-expressing cells were characterized by a malignant morphology. Our findings might represent the basis for the clinical application of secretagogin as a biomarker for a distinct subgroup of colorectal cancers.
    PROTEOMICS 06/2006; 6(9):2916-23. · 4.13 Impact Factor
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    ABSTRACT: Pulmonary epithelium is known to undergo a preneoplastic process prior to the development of lung carcinoma. Squamous dysplasia and atypical adenomatous hyperplasia have been identified and classified as preinvasive lesions of squamous cell carcinoma and peripheral pulmonary adenocarcinoma, respectively. However, these commonly recognized preinvasive lesions do not completely explain the development of all histological types of lung carcinoma. By examining 114 resection lung specimens, we concluded that there are four histological patterns of bronchial epithelial dysplasia based on morphological features (basal cell dysplasia, columnar cell dysplasia, bronchial epithelial dysplasia with transitional differentiation, and squamous dysplasia). The histological patterns were further characterized by immunohistochemistry. Basal cell dysplasia was focally positive for cytokeratin (CK) 17 and 10/13; columnar cell dysplasia was generally positive for CK7, 8, and 18; bronchial epithelial dysplasia with transitional differentiation had a heterogeneous immunoprofile, while squamous dysplasia was positive for CK10/13 and focally positive for CK17. Various degrees of abnormal expression of p53 and Ki-67 were found in the different types of bronchial epithelial dysplasia. The cases were divided into three groups based on degree and extent of bronchial epithelial dysplasia. By Crosstabs McNemar test, the Mann-Whitney U-test (for two independent groups), the Kruskal-Wallis one-way nonparametric ANOVA (for >2 independent groups) and Spearman correlation analysis, the degree and extent of bronchial epithelial dysplasia was shown to be positively correlated with the incidence of bronchogenic carcinoma and multifocal primary lung carcinoma (P<0.05). These findings indicated the following: (1) bronchial epithelium can develop various patterns of dysplasia with abnormal/ambiguous cell differentiation and abnormal expressions of p53 and Ki-67. Thus, these bronchial epithelial dysplastic lesions may represent a preneoplastic process. (2) The degree of bronchial epithelial dysplasia may significantly predispose individuals to bronchogenic carcinoma and multifocal primary lung carcinoma.
    Modern Pathology 04/2006; 19(3):429-37. · 5.25 Impact Factor