Xiao-Ping Huang

Chongqing Cancer Hospital and Institute, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (16)34.01 Total impact

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    ABSTRACT: To detect DNA copy number abnormality and LOH and explore the profile of chromosomal imbalances in esophageal atypical hyperplasia and early stage esophageal squamous cell carcinoma using SNP array. The DNA copy number abnormality and LOH in pathological change esophageal tissue and matched normal esophageal tissue of one case of primary esophageal high atypical hyperplasia and four cases of primary early stage esophageal squamous cell carcinoma were detected by using Affymetrix GeneChip Human Mapping 250K Nsp Array. Amplification was found in a few DNA fragment and no deletion or LOH was found in esophageal high atypical hyperplasia. In early stage esophageal squamous cell carcinoma, DNA amplification occurred in 1p, 1q, 2p, 2q, 3q, 4q, 5p, 6p, 6q, 7q, 8q, 11p, 11q, 12p, 12q, 14q, 17q, 18p, 19q, 20q, 22q and X chromosome. DNA deletion occurred in 1p, 2q, 3p, 3q, 4p, 4q, 8p, 9p, 9q, 10q, 11p, 13q, 16p, 18q, 19p, 19q and 22q chromosome. LOH occurred in 3q and 9q chromosome. The amplification in 1p, 19q, 4q, 11p chromosome and the deletion in 3q, 11p, 2q, 16p chromosome were rarely reported. DNA abnormality was rare in esophageal high atypical hyperplasia. The obvious amplification and deletion in DNA have been found in early stage esophageal squamous cell carcinoma, but LOH was rarely found. 250K SNP array could effectively detect DNA copy number change and LOH in whole-wide genes in esophageal atypical hyperplasia and early stage esophageal squamous cell carcinoma with high distinguishability and precise location. The results would provide important academic information for detection and location of related genes in early stage esophageal squamous cell carcinoma.
    No preview · Article · Nov 2008 · Zhonghua yi xue za zhi
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    ABSTRACT: Mucosal iodine staining has improved the detection of precancerous lesions of the esophagus. However, this method is unable to exactly evaluate the risk status of the lesions. In the present study, we conducted a molecular analysis combining the iodine staining in esophageal squamous cell carcinomas (ESCC) and different premalignant lesions of the esophagus in order to improve the early diagnosis of ESCC. Tumorous and precancerous lesions were procured as iodine-unstained areas in the resected specimens of ESCC patients by means of Lugol's iodine staining. Loss of heterozygosity (LOH) was detected with 35 microsatellite markers frequently reported to be deleted in ESCC. The markers with high frequency of LOH in tumorous and precancerous lesions of the same patient were subjected to further detection in iodine-unstained biopsy samples from the population screening in ESCC high-incidence region. Common alterations were observed at D3S3644, D3S1768, D3S3040, D3S4542, RPL14, D9S169, D13S171 and D13S263 in both cancer tissues and precancerous lesions around tumors. Interestingly, D3S3644, D3S1768, D3S3040, D3S4542, RPL14 and D13S263 were also found with high frequency of LOH in iodine-staining abnormal lesions from the population screening. Most importantly, LOH frequency increased with histological severity. Our data suggest that detection of these six markers in combination with iodine staining might contribute to the prediction for the risk of ESCC development and for the diagnosis of patients in preclinical and preneoplastic phase of the disease.
    No preview · Article · Apr 2008 · Journal of Cancer Research and Clinical Oncology
  • Xiao-Ping Huang · Xu Zhang · Xiao-Dong Su · Guo-Wei Ma · Jin-Ming Zhao · Tie-Hua Rong
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    ABSTRACT: MCM4 belongs to minichromosome maintenance (MCM) protein family. It is a DNA replication licensing factor. This study was to explore the expression and significance of MCM4 in esophageal squamous cell cancer (ESCC). The expression of MCM4 in 60 specimens of ESCC, paracancer esophageal epithelia, and distant normal esophageal epithelia was detected by reverse transcription-polymerase chain reaction (RT-PCR). The Correlations of MCM4 expression to clinicopathologic features of the 60 ESCC patients were analyzed. The positive rate of MCM4 was significantly higher in ESCC than in paracancer esophageal epithelia (65.0% vs. 33.3%, P<0.001); MCM4 was not expressed or weakly expressed in distant normal esophageal epithelia. The positive rate of MCM4 was significantly higher in stage T3 ESCC than in stage T1 ESCC (73.7% vs. 25.0%, P<0.05). The expression of MCM4 had no correlations to grade, lymph node metastasis, sex, and age. The expression of MCM4 might be related to the pathologic stage of ESCC.
    No preview · Article · Feb 2007 · Ai zheng = Aizheng = Chinese journal of cancer
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    ABSTRACT: To investigate the expression of the human mammoglobin (hMAM) mRNA in bone marrow and its clinical significance in the breast cancer patient. Expression of hMAM mRNA was detected using nested reverse transcription polymerase chain reaction (RT-PCR) in the bone marrow aspiration sample from 75 breast cancer patients, 15 patients with benign breast lesions and 8 healthy volunteers as control. The possible correlation of hMAM mRNA expression with clinico-pathological parameters and related molecular markers such as Ki67, p53 and VEGF were analyzed. The sensitivity of RT-PCR in this series reached 10(-6). The hMAM mRNA was found to be positively expressed by RT-PCR in 21 of 75 breast cancer patients with a positive rate of 28.0%. However, hMAM mRNA expression was not detected in the bone marrow aspiration samples from patients with benign breast lesions and healthy volunteers. The hMAM mRNA expression was positively correlated with axillary nodal involvement and progesterone receptor (PR) status (P < 0.05) as well as Ki67 expression in breast cancer tissue (chi2 = 4.936, P = 0.026), but not with age, tumor size, clinical stage, or estrogen receptor (ER) status (P > 0.05). RT-PCR is quite sensitive and has a high specificity in detecting the presence of hMAM mRNA in the bone marrow from breast cancer patients. Thereupon, hMAM mRNA may be useful as a molecular biomarker in detecting disseminated tumor cells (DTC) in the bone marrow of breast cancer patients. Positive hMAM mRNA expression result may have an impact upon therapeutic recommendations and patients' prognostic judgement.
    No preview · Article · Nov 2006 · Zhonghua zhong liu za zhi [Chinese journal of oncology]
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    ABSTRACT: Second mitochondrial activator of caspase (Smac) was recently identified as a new apoptogenic factor that is released from mitochondria. It promotes apoptosis by antagonizing inhibitor of apoptosis proteins, and shows in vitro antitumor effect. However, little is known about its role in non-small cell lung cancer (NSCLC). This study was to investigate the expression of Smac in stage I-II NSCLC, and explore its correlations to clinicopathologic features and prognosis. Immunohistochemistry and tissue microarray were used to detect the expression of Smac in 213 specimens of stage I-II NSCLC. Its correlations to clinicopathologic features and prognosis of NSCLC were analyzed. The 5-year survival rate of the patients with stage I NSCLC was 61.9%, and that of the patients with stage II NSCLC was 30.0%. Smac protein was mainly localized in cytoplasm. When the positive cells percentage of 75% was used as a cutoff point, 129 (39.4%) samples showed high Smac expression, and 84 (60.6%) showed low Smac expression. Smac expression was not correlated to sex, age, histological type, blood type and prognosis of the patients, whereas the positive rate of Smac was significantly higher in the patients with lymph node metastasis than in the patients without lymph node metastasis (58.3% vs. 37.0%, P<0.05). Smac protein might be correlated to lymph node metastasis of NSCLC.
    No preview · Article · Jun 2006 · Ai zheng = Aizheng = Chinese journal of cancer
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    ABSTRACT: Chromosomal aberrations (amplifications and deletions) underlie the genesis or development of cancer. Amplification of 8q24 is one of the most frequent events in esophageal cancer. To define whether C-MYC is the target gene for 8q24 amplification, we performed fluorescence in situ hybridization using a MYC (8q24.12 approximately q24.13) probe in esophageal cancer from southern China. Furthermore, we detected the expression status of several genes including C-MYC, TRIB1 (alias C8FW), and FAM84B (alias NSE2) in the regions of 8q24 via reverse transcriptase-polymerase chain reaction or immunohistochemical analysis (or both). Distinct amplification of 8q24 was found in esophageal carcinomas. Only 4 of 46 cases showed obvious protein expression in part of the esophageal cancerous nest. In particular, increased protein expression of C-MYC was shown only in a small part of a cancerous nest in the four cases. Positive C-MYC staining was detected mainly in the cytoplasm of esophageal cancer cells. No expression of TRIB1 was detected in esophageal squamous cell carcinomas. Of 59 cases, 39 (66%) cases showed increased expression of FAM84B in esophageal carcinomas. The results suggest that C-MYC and TRIB1 may not be the amplification target of 8q24 in esophageal cancer. FAM84B might be involved in the genesis or development of esophageal cancer in southern China. Whether FAM84B is the amplification target of esophageal cancer awaits further investigation.
    No preview · Article · Mar 2006 · Cancer Genetics and Cytogenetics
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    ABSTRACT: Allelic loss on chromosome 3p occurs frequently in esophageal cancer. The human ribosomal protein L14 gene (RPL14) is located on chromosome 3p21.3. In the present study, we investigated alteration of RPL14 at both the genomic DNA and RNA levels in 129 Chinese esophageal squamous cell carcinomas (ESCC) and 17 dysplasia adjacent to tumor tissues by a combination of tissue microdissection, microsatellite analysis of the intragenic marker, reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing. In the tested informative cases, loss of heterozygosity (LOH) of RPL14 was observed in 29 out of 68 (43%) tumors. Decreased expression of the gene was detected in 31 out of 49 (63%) carcinomas. No mutation was found in the remaining RPL14 allele of the tumors with LOH. We examined subsequently the allelic status of RPL14 in the dysplasia (preneoplastic lesions) between malignant tissues and histologically normal epithelia. Of 17 tested dysplasia in which the tumors showed LOH, eight (47%) displayed the same allelic loss as their corresponding tumors, seven (41%) exhibited microsatellite instability (MSI), and only two retained both the RPL14 alleles. The data suggest that alteration of RPL14 occurred frequently in ESCC and might be an earlier event in the tumorigenesis of the esophagus. Analysis to RPL14 gene may contribute to the early detection of ESCC as a potential molecular marker.
    No preview · Article · Feb 2006 · Gene
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    ABSTRACT: Chromosome 13 presents frequent allelic loss in esophageal squamous cell carcinomas (ESCC). However, no ESCC suppressor gene has been identified from this chromosome. To define common deletion regions that possibly contain the ESCC suppressor gene(s), we performed a mapping of allelic loss in 50 esophageal squamous cell carcinomas using a panel of 25 microsatellite markers on chromosome 13q21-qter, which has rarely been studied for allelic loss. Loss of heterozygosity (LOH) with high frequencies (> or = 50%) was observed at markers D13S1494, D13S1323, D13S248, D13S1315, D13S285, and D13S1295, in which the peak LOH (69.2%) was at locus D13S248. Seven cases presented LOH at three consecutive markers D13S248, D13S1315 and D13S285, 4 of which also displayed LOH at another adjacent marker D13S1295. This overlapping region of deletion covers an interval of 6.36 Mb at 13q33.1-q34, whose deletion has not previously been reported in ESCC. Tumors of grade II showed significantly more frequent LOH at D13S248 than those of grade I. A significantly higher frequency of allelic loss at D13S152 was also found in tumors with lymph node metastasis compared to those without lymph node metastasis. The present study defined a novel region of allelic loss in 13q33-q34. LOH at D13S248 and D13S152 are associated with higher tumor grade and metastasis, respectively.
    No preview · Article · Dec 2005 · Oncology Reports
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    ABSTRACT: MCM4 is a member of Minichromosome maintenance protein family. MCM2-7 proteins play an essential role in eukaryotic DNA replication and have been identified as components of DNA replication licensing factors. So far, no research on MCM4 has been reported in esophageal cancer. In this study, we detected via RT-PCR the expression status of MCM4 in esophageal cancer from southern China and therefore disclose the relationship between MCM4 and esophageal cancer. 65% (39/60) cases showed increased expression of MCM4 in the carcinomas when compared with normal esophageal epithelia in which no or low MCM4 expression was detected in most cases. Twenty of sixty cases (33%) showed increased expression of MCM4 in the adjacent epithelia. Furthermore, MCM4 expression in esophageal carcinomas was significantly higher than the one in the adjacent epithelia (chi square value is 12.037, P < 0.001). Significant difference for the expression status of MCM4 was found between the patients with histopathological stage T3 and stage T1 (chi square value = 4.038, P < 0.05). The increased expression of MCM4 might be associated with pathological staging of esophageal cancer. The alterations of MCM4 are possibly related to the earlier event of esophageal carcinogenesis. MCM4 is probably a valuable molecular marker involved in the development and/or genesis of esophageal cancer.
    No preview · Article · Oct 2005 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: TNM staging system is used widely to predict prognosis of non-small cell lung carcinoma (NSCLC) patients, but patients with the same stage may have very different survivals; better prognostic index is needed. Angiogenesis is considered to be essential for tumor development, progression, and metastasis, but the prognostic impacts of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in NSCLC is controversial. This study was to evaluate the prognostic value of VEGF and MVD in NSCLC. VEGF and MVD in 214 specimens of stageI-II NSCLC (20 in stage IA, 137 in stage IB, and 57 in stage IIB) were detected by tissue chip and SP immunohistochemistry. No patient underwent postoperative antitumor treatment. VEGF expression didn't relate to gender, age, blood type, pathologic type, and TNM stage (P0.05). MVD correlated with age and pathologic type (P0.05), but did not relate to gender, blood type, and TNM stage (P0.05). The mean value of MVD was 65.8+/-5.2 in VEGF-low patients, and 67.5+/-2.5 in VEGF-high patients (P0.05). The 5-year survival rate was significantly lower in MVD-high patients than in MVD-low patients (34.5% vs. 60.0%, P=0.013). Furthermore, multivariate Cox regression analysis showed that MVD (P=0.000) was an independent prognostic factor of NSCLC. High MVD closely relates to poor prognosis of stageI-II NSCLC.
    No preview · Article · Aug 2005 · Ai zheng = Aizheng = Chinese journal of cancer
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    ABSTRACT: Breast cancer may undergo metastasis in early phase. Distant metastasis, especially bone metastasis, may influence prognosis of breast cancer patients. Bone marrow micrometastasis (BMM) is difficult to detect with routine methods. This study was designed to evaluate expression and clinical significance of cytokeratin 19 (CK19) in bone marrow of patients with breast cancer. Expression of CK19 mRNA in bone marrows of 65 breast cancer patients, 15 benign breast disease patients, and 8 healthy volunteers was detected by reverse transcription-polymerase chain reaction (RT-PCR). Correlation of CK19 mRNA expression to clinicopathologic features of the 65 breast cancer patients was analyzed. Positive rate of CK19 mRNA was 33.8% in the 65 breast cancer patients, and 0 in both benign breast disease patients and healthy volunteers. Expression of CK19 mRNA was positively correlated with tumor size and clinical stage (P < 0.05), but was not related to age and lymph node status (P > 0.05). In addition, positive rate of CK19 mRNA was positively correlated with carcinoembryonic antigen (CEA) in peripheral blood (r=0.372, P=0.002). CK19 mRNA may be used as a molecular marker to detect bone marrow micrometastasis in patients with breast cancer. The detection may help to select proper therapy and predict prognosis of breast cancer patients.
    No preview · Article · Jul 2005 · Ai zheng = Aizheng = Chinese journal of cancer
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    ABSTRACT: To investigate the alteration of the gene HSD17B4 in esophageal squamous cell carcinoma and its potential significance. The mRNA expression and loss of heterozygosity (LOH) of HSD17B4 in 40 primary esophageal tumors were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and microsatellite analysis with the intragenic marker D5S1384 of the gene. The frequencies of allelic loss of D5S1384 and the rate of down-regulation of gene HSD17B4 were 46.2% and 62.5%, respectively. HSD17B4 may be a candidate tumor suppressor gene associated with esophageal squamous cell carcinoma.
    No preview · Article · Jul 2005 · Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
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    ABSTRACT: Human MLH1 is one of the DNA mismatch repair genes and located in chromosome 3p21.3. Alterations of the MLH1 were associated with various kinds of human tumors. The present study was to investigate allelic loss of MLH1 and microsatellite instability (MSI) in esophageal squamous cell carcinomas (ESCC), and to estimate the correlation between MSI status and allelic loss of the MLH1 gene. The MSI of 14 microsatellite markers and mRNA expression of MLH1 were assessed in a large cohort of patients with ESCC by using denaturing polyacrylamide gel electrophoresis (PAGE) and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. Thirty-five percent of tumors displayed MSI in at least one tested marker. MSI in D3S1611, an intragenic marker of the MLH1, was observed in 66.7% of tumors. No down-expression of MLH1 was found at the transcriptional level. The presence of MSI did not correlate with tumor stage, degree of differentiation, lymphonode-metastasis, age and sex of the patients, neither with allelic loss of the MLH1 gene. The data suggested that LOH of MLH1 is common in ESCC, but not lead to the alteration of MLH1 at the level of RNA expression. MSI in tested microsatellite markers occurs frequently in ESCC but is not associated with allelic loss of the MLH1 gene.
    Preview · Article · Apr 2005 · Acta Genetica Sinica
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    ABSTRACT: The existence of unknown tumor suppressor gene(s) other than the APC gene has been hinted on 5q for esophageal squamous cell carcinoma (ESCC). In order to define minimal deletion intervals on 5q in ESCC and investigate the potential tumor suppressor gene(s), 9 microsatellite markers scattering the region from 5q22 to 5q35 were chosen for loss of heterozygosity (LOH) analysis in 50 primary ESCC from northern China. The results showed that six cases presented coexistence of LOH for three consecutive adjacent chosen markers, suggesting a minimal deletion region covering approximately 272 kb located on 5q23 from D5S1384 to D5S1505. It was a novel deletion region that was so far never reported in ESCC. Significant higher frequencies of LOH were observed in tumors with lower pathological grade at the locus D5S820 and with lymph node metastasis at the locus D5S408. The data suggested the possibility that one or more putative candidate tumor suppressor gene(s) on 5q23 might play an important role in the development and/or progression of ESCC.
    No preview · Article · Dec 2004 · Cancer Letters
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    ABSTRACT: Deletions and translocations involving the short arm of chromosome 3 (3p14) have been observed frequently in esophageal cancer. Fragile histidine triad (FHIT) gene is located in 3p14.2, and its deletion or abnormal expression was found in many kinds of cancers. The study was to investigate the alterations of FHIT gene, and its significance in esophageal squamous cell carcinoma (ESCC). The deletion of FHIT gene in 80 cases of ESCC was evaluated by microsatellite analysis, and the mRNA expression of FHIT gene in 20 cases of ESCC was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Intragenic markers of FHIT gene, D3S3356, D3S3378, and D3S3361, showed homozygous in all samples. D3S1234 and D3S1540, located near FHIT, presented high heterozygosity. In the tested informative cases, loss of heterozygosity (LOH) of D3S1234 was detected in 30 out of 52 tumors (57.69%), and that of D3S1540 was observed in 38 out of 56 carcinomas (67.86%). Reduced expression of FHIT mRNA occurred in 15 of 20 (75.00%) cases, and was often accompanied with LOH. However, the FHIT down-regulation was not always coincident with LOH. The abnormal expression of FHIT gene occurred frequently in ESCC. LOH was the main factor leading to down-regulation of FHIT expression. Epigenetic mechanism might be associated with reduced expression of FHIT in a part of ESCC cases.
    No preview · Article · Sep 2004 · Ai zheng = Aizheng = Chinese journal of cancer
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    ABSTRACT: p63 is a recently identified homologue of the tumor suppressor gene TP53, which encodes multiple isotypes with transactivating, death-inducing and dominant-negative activities. p63 is expressed in basal cells of squamous epithelia and many kinds of tumors. To explore the penetrance of p63 in esophageal cancer, we analyzed p63 expression in squamous cell carcinomas, adjacent dysplasia and histologically normal mucosa of the esophagus by combination of immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the DeltaNp63 mRNA was easily detectable in all malignant and histologically normal tissues, whereas TAp63 presented extremely low or no expression. The p63 protein was highly expressed in 50 of 51 tumor tissues without significant difference in gender, age, stage and grade. Ten of 11 dysplasia exhibited strong p63 staining in all abnormal cells. Interestingly, p63 expression was observed in 96% (45/47) histologically normal epithelia adjacent to the cancerous tissues but only in 47% (14/30) mucosa far from tumors. Most of the epithelia far from tumors showed weaker staining than that adjacent to the cancerous tissues. In all the histologically normal epithelia with p63 expression, irrespective of the distance from the tumors, immunohistochemical reaction was restricted to the basal and suprabasal cell layers. Our data suggested that DeltaNp63 is the major isotype expressed in epithelia and tumors of the esophagus. Elevated expression of p63 is probably an early event in esophageal squamous cell carcinomas, which may play a significant role in the development of the disease.
    Preview · Article · Dec 2002 · International Journal of Cancer

Publication Stats

143 Citations
34.01 Total Impact Points


  • 2008
    • Chongqing Cancer Hospital and Institute
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2005-2006
    • Sun Yat-Sen University
      • Department of Thoracic Surgery
      Shengcheng, Guangdong, China
  • 2002-2006
    • Peking Union Medical College Hospital
      Peping, Beijing, China