Publications by authors named "Huamei Tang"

67 Publications

Proteomics Analysis Reveals Bacterial Antibiotics Resistance Mechanism Mediated by Against Enoxacin in .

Front Microbiol 2021 8;12:699415. Epub 2021 Jun 8.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.

Bacterial antibiotic resistance is a serious global problem; the underlying regulatory mechanisms are largely elusive. The earlier reports states that the vital role of transcriptional regulators (TRs) in bacterial antibiotic resistance. Therefore, we have investigated the role of TRs on enoxacin (ENX) resistance in in this study. A label-free quantitative proteomics method was utilized to compare the protein profiles of the knockout and wild-type strains under ENX stress. Bioinformatics analysis showed that the deletion of triggers the up-regulated expression of some vital antibiotic resistance proteins in upon ENX stress and thereby reduce the pressure by preventing the activation of SOS repair system. Moreover, directly or indirectly induced at least 11 TRs, which indicates a complicated regulatory network under ENX stress. We also deleted six selected genes in that altered in proteomics data in order to evaluate their roles in ENX stress. Our results showed that genes such as , , , , and are regulated by and may be involved in ENX resistance. Overall, our data demonstrated the important role of in ENX resistance and provided novel insights into the effects of transcriptional regulation on antibiotic resistance in bacteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.699415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217646PMC
June 2021

A Fully Automated and Integrated Microfluidic System for Efficient CTC Detection and Its Application in Hepatocellular Carcinoma Screening and Prognosis.

ACS Appl Mater Interfaces 2021 Jun 18;13(25):30174-30186. Epub 2021 Jun 18.

Department of General Surgery, Department of Pathology, Department of Ultrasound, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China.

Analysis of circulating tumor cells (CTCs) is regarded as a useful diagnostic index to monitor tumor development and guide precision medicine. Although the immunoassay is a common strategy for CTC identification and heterogeneity characterization, it is challenged by poor reaction efficiency and laborious manipulations in microdevices, which hinder the sensitivity, throughput, simplification, and applicability. To meet the need for rapid, sensitive, and simple CTC analysis, we developed an efficient CTC detection system by integrating a 3D printed off-chip multisource reagent platform, a bubble retainer, and a single CTC capture microchip, which can achieve CTC capture and identification within 90 min. Compared with traditional CTC identification methods, this system decreases immunostaining time and antibody consumption by 90% and performs the on-chip immunoassay in a fully automated manner. Using this system, CTCs from the peripheral blood of 19 patients with various cancers were captured, detected, and compared with clinical data. The system shows great potential for early screening, real-time monitoring, and precision medicine for hepatocellular carcinoma (HCC). With the advantages of automation, stability, economy, and user-friendly operation, the proposed system is promising for clinical scenarios.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c06337DOI Listing
June 2021

Proteomics analysis reveals the importance of transcriptional regulator slyA in regulation of several physiological functions in Aeromonas hydrophila.

J Proteomics 2021 07 24;244:104275. Epub 2021 May 24.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, PR China; Key Laboratory of Crop Ecology and Molecular Physiology, Fujian Agriculture and Forestry University, Fuzhou, PR China; Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou 350002, PR China. Electronic address:

SlyA is a well-known transcription factor that plays important roles in the regulation of diverse physiological functions including virulence and stress response in various bacterial species. The biological effects of slyA have species-specific characteristics. In this study, a phenotype assay showed that slyA gene deletion in Aeromonas hydrophila (ahslyA) decreased biofilm formation capability but did not affect bacterial hemolytic activity or acid stress response. The differentially expressed proteins between ΔahslyA and wild-type strains were compared by label-free quantitative proteomics to further understand the effects of AhSlyA on biological functions. Bioinformatics assays showed that ΔahslyA may be involved in the regulation of several intracellular metabolic pathways such as galactose metabolism, arginine biosynthesis, and sulfur metabolism. A further phenotypic assay confirmed that AhSlyA plays an important role in the regulation of sulfur and phosphate metabolism. Moreover, ahslyA also directly or indirectly regulated at least eight outer membrane proteins involved in the maintenance of cell permeability. Overall, the results provide insights into the functions of ahslyA and demonstrate its importance in A. hydrophila. BIOLOGICAL SIGNIFICANCE: In this study, we compared the DEPs between the transcriptional regulator slyA-deleted and the wild-type A. hydrophila strains using a label-free quantitative proteomics method. The bioinformatics analysis showed that slyA may be involved in the regulation of several metabolic pathways. Subsequent phenotype and growth assays confirmed that ΔahslyA affected sulfur and phosphate metabolism, and OM permeability. Finally, a ChIP-PCR assay further confirmed that AhSlyA directly binds to the promoters of several candidate genes, including sulfur metabolism-related genes. These results indicated that slyA plays an important regulatory role in pleiotropic physiological functions of A. hydrophila, and these functions may be different from those identified in previous reports from other bacterial species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jprot.2021.104275DOI Listing
July 2021

The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy.

Oncogene 2021 Jun 14;40(23):3974-3988. Epub 2021 May 14.

Department of General Surgery, Xiang An Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2-p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01815-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195740PMC
June 2021

Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis.

Cell Death Dis 2021 04 12;12(4):390. Epub 2021 Apr 12.

Organ Transplantation Institute of Xiamen University, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, China.

Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 (NRP1) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03672-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042018PMC
April 2021

Analytical performance evaluation of five RT-PCR kits for severe acute respiratory syndrome coronavirus 2.

J Clin Lab Anal 2021 Jan 27;35(1):e23643. Epub 2020 Oct 27.

Anhui University of Science and Technology, Huainan, China.

Background: We aimed to evaluate the analytical performance of five commercial RT-PCR kits (Genekey, Daan, BioGerm, Liferiver, and Yaneng) commonly used in China, since such comparison data are lacking.

Methods: A total of 20 COVID-19 confirmed patients and 30 negative nasopharyngeal swab specimens were analyzed by five kits. The detection ability of five RT-PCR kits was evaluated with 5 concentration gradients diluted by a single positive sample. The limit of detection was evaluated by N gene fragment solid standard. Two positive clinical specimens were used to evaluate the repeatability and imprecision. Finally, we used six human coronaviruses plasmid and four respiratory pathogens plasmid to check for cross-reactivity.

Results: The positive detection rate was 100% for Genekey, Daan, and BioGerm,and 90% for Liferiver and Yaneng in 20 clinical SARS-CoV-2 infection. The coincidence rate of five kits in 10 negative samples was 100%. The detection rate of target genes for Daan, BioGerm, Liferiver, and Yaneng was 100% from Level 1 to Level 3. In Level 4, only Daan detection rate was 100%. In Level 5, five kits presented poor positive rate. The limit of detection declared by each manufacturer was verified. The repeatability for target genes was less than 5% and so did the total imprecision. There is no cross-reactivity of five kits with six human coronaviruses and four respiratory pathogens for ORF1ab and N gene.

Conclusions: Five RT-PCR kits assessed in this study showed acceptable analytical performance characteristics and are useful tools for the routine diagnosis of SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645906PMC
January 2021

Consistency evaluation of Liferiver, Yaneng, Darui, and the Cobas 4800 test for high-risk human papillomavirus screening.

J Clin Lab Anal 2020 Dec 19;34(12):e23536. Epub 2020 Aug 19.

Medical Laboratory of the Third Affiliated Hospital of ShenZhen University, Shenzhen, China.

Background: In recent years, several high-risk human papillomavirus (HR-HPV) tests have been developed. The assay capabilities need to be systematically reviewed. Here, we compared the clinical sample performance of three novel HR-HPV assays (Liferiver, Yaneng, and Darui) based on different platforms with the widely adopted cobas4800 test.

Methods: A total of 346 cervical swabs from women who were screened for cervical cancer were analyzed for the presence of 14 HR-HPV genotypes. The distinction between the four assays was investigated by the genotyping and direct sequencing.

Results: The positive rates of the four assays ranged from 61.56% to 64.16%. The overall concordance was 88.15%. The Yaneng assays displayed the best sensitivity (100%) and specificity (98.43%). The sensitivity (98.17%) and specificity (98.43%) of the Darui assay were superior to those of the cobas4800 test (97.72% and 93.70%, respectively). The Liferiver assay displayed comparable sensitivity with the cobas4800 test (95.89% and 97.72%, respectively). The specificity of the cobas4800 was lower than that of the Liferiver assay (93.70% vs. 97.64%).

Conclusions: The three novel HR-HPV assays displayed good agreement with the cobas4800 test. The analytical performance of all four fulfilled the requirements of sensitivity and specificity for HR-HPV detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755768PMC
December 2020

Evaluation on the separated effect of 13 hemoglobin variants by a new automatic Hba1c analyzer.

J Clin Lab Anal 2020 Oct 12;34(10):e23446. Epub 2020 Jul 12.

Medical Laboratory of Shenzhen Luohu People's Hospital, Shenzhen, China.

Objective: To evaluate the effect of a new type of automatic glycated hemoglobin analyzer on the separation of abnormal hemoglobin.

Methods: Samples diagnosed as hemoglobin variants by capillary electrophoresis and gene testing were selected, and HbA1c analyzer was used for separation and detection.

Results: A total of 13 hemoglobin variants in 40 samples could be separated from the normal peaks.

Conclusions: The variant mode of hemoglobin HbA1c can identify a variety of hemoglobin variants, and the type of variants can be preliminarily determined according to the retention time and characteristic peak shape of the variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595897PMC
October 2020

Development of a novel prognostic signature for predicting the overall survival of bladder cancer patients.

Biosci Rep 2020 06;40(6)

Medical Laboratory of the Third Affiliated Hospital of Shenzhen University, Shenzhen 518001, China.

Background: Bladder cancer is one of the most common malignancies. So far, no effective biomarker for bladder cancer prognosis has been identified. Aberrant DNA methylation is frequently observed in the bladder cancer and holds considerable promise as a biomarker for predicting the overall survival (OS) of patients.

Materials And Methods: We downloaded the DNA methylation and transcriptome data for bladder cancer from The Cancer Genome Atlas (TCGA), a public database, screened hypo-methylated and up-regulated genes, similarly, hyper-methylation with low expression genes, then retrieved the relevant methylation sites. Cox regression analysis was used to identify a nine-methylation site signature of a training group. Predictive ability was validated in a test group by receiver operating characteristic (ROC) analysis.

Results: We identified nine bladder cancer-specific methylation sites as potential prognostic biomarkers and established a risk score system based on the methylation site signature to evaluate the OS. The performance of the signature was accurate, with area under curve was 0.73 in the training group and 0.71 in the test group. Taking clinical features into consideration, we constructed a nomogram consisting of the nine-methylation site signature and patients' clinical variables, and found that the signature was an independent risk factor.

Conclusions: Overall, the significant nine methylation sites could be novel prediction biomarkers, which could aid in treatment and also predict the overall survival likelihoods of bladder cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20194432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286875PMC
June 2020

Internal Spreading of Papillary Thyroid Carcinoma: A Case Report and Systemic Review.

Case Rep Endocrinol 2018 8;2018:7618456. Epub 2018 Jan 8.

Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, China.

An 18-year-old female diagnosed finally as PTC with intrathyroid spread was reported, and the diagnosis and surgical treatment of internal spreading of PTC were discussed. One lump was found on the thyroid isthmus by physical examination and B ultrasound, and multiple nodular shadows were found by CT. This patient finally underwent total thyroidectomy with bilateral central node dissection due to multifocal papillary thyroid carcinoma except PTC in the isthmus found in right lobe by intraoperative frozen section. The pathological section showed a major thyroid carcinoma in thyroid isthmus with scattered micropapillary carcinoma around it in the whole thyroid gland. The small lesions are distributed around central lesion in a radial form and the number of small lesions decreases with increased distance from central lesion. PTC with internal spread should be distinguished from multifocal PTC and poorly differentiated PTC in pathology. Thyroid cancerous node had a large diameter; it was likely to have internal spread. Combined imaging before surgery should be valued to diagnose PTC with internal spread. Preoperative CT and intraoperative frozen section are helpful for surgical volume selection of PTC with internal spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/7618456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817257PMC
January 2018

HOXA13 contributes to gastric carcinogenesis through DHRS2 interacting with MDM2 and confers 5-FU resistance by a p53-dependent pathway.

Mol Carcinog 2018 06 27;57(6):722-734. Epub 2018 Feb 27.

Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

5-FU-based chemotherapy is recently most recommended as the first-line treatment for gastric cancer (GC). However, 5-FU resistance is common for many postoperative GC patients. Homeobox A13 (HOXA13) is a member of homeobox genes highly expressed in many human tumors. Its potential roles and mechanisms of resistance to 5-FU in GC are poorly understood. In this study, we discovered that HOXA13 played an oncogenic role in vivo and in vitro. The patients with HOXA13 overexpression were closely related with poor prognosis and more prone to be resistant to 5-FU. Moreover, dehydrogenase/reductase 2 (DHRS2) was identified as a downstream gene of HOXA13. HOXA13 played a role of carcinogenesis through directly down-regulating DHRS2 to increase MDM2. Furthermore, HOXA13 conferred 5-FU resistance through MRP1 by a p53-dependent pathway. Therefore, HOXA13 might serve as a potential signature that recognized patients who were insensitive to 5-FU, and timely recommended them to other chemotherapy regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mc.22793DOI Listing
June 2018

Correction to: Metalloproteases meprin-ɑ (MEP1A) is a prognostic biomarker and promotes proliferation and invasion of colorectal cancer.

BMC Cancer 2018 01 11;18(1):70. Epub 2018 Jan 11.

Department of General Surgery, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai, 200080, China.

Correction: After publication of the original article [1] the authors found that the figure contained an incorrect version of Fig. 3a. This does not affect the results and conclusions of the article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-017-3767-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763604PMC
January 2018

Up-regulation of CIT promotes the growth of colon cancer cells.

Oncotarget 2017 Sep 27;8(42):71954-71964. Epub 2017 Jun 27.

Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 200080, People's Republic of China.

Colon cancer is one of the major causes of cancer mortality worldwide. However, the underlying mechanism and therapeutic targets of colon cancer have not yet been fully elucidated. In the present study, we demonstrate that citron rho-interacting, serine/threonine kinase 21 (CIT) promotes the growth of human colon cancer cells. CIT is overexpressed in human colon cancer tissues and cell lines. High expression of CIT predicts poor survival for patients with colon cancer. In colon cancer cells, CIT knockdown represses cellular proliferation and colony formation. Our xenograft experiments showed that CIT knockdown reduces the growth rate of colon cancer cells and the final tumor weight. We found that CIT knockdown induces cell cycle arrest and apoptosis in colon cancer cells. Further microarray and bioinformatics analyses indicated that CIT regulates the p53 signaling pathway, which may account for the effects of CIT on colon cancer cells. Taken together, our findings provide evidence that CIT may promote the development of colon cancer, at least in part, through the p53 signaling pathway. Therefore, CIT may be a potential therapeutic target for colon cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.18615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641103PMC
September 2017

miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2.

Mol Ther Nucleic Acids 2017 Jun 12;7:453-464. Epub 2017 May 12.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address:

5-Fluorouracil (5FU)-based adjuvant therapy is the first-line therapy for treating stage II and III colon cancer after surgery. However, its therapeutic efficacy is limited because of chemoresistance, especially in deficient mismatch repair (dMMR) colon cancer. Here, we first used laser capture microdissection to obtain purified cells from four dMMR and four proficient mismatch repair (pMMR) colon cancer tissues. Second, microRNA (miRNA) microarray chips were used to identify miRNAs that are differentially expressed between these two classes of tumors. Third, we analyzed their differential expression by qRT-PCR in a panel of 5-FU-resistant colon cancer cell lines. We identified that miR-1290 was one of the most upregulated miRNAs in both dMMR colon cancer tissues and 5-FU-resistant cells. We also found that miR-1290 was positively correlated with dMMR status and predicted poor prognosis in stage II and III colon cancer patients who received 5-FU-based chemotherapy. Furthermore, we demonstrated that inhibition of the expression of miR-1290 enhanced sensitivity to 5-FU treatment in vitro and in tumor xenografts in vivo by direct targeting hMSH2. Our study indicates that miR-1290 may become a promising biomarker of dMMR colon cancer and predicts the prognosis of stage II and III patients who receive 5-FU-based adjuvant therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtn.2017.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443909PMC
June 2017

miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGFβ-mediated epithelial to mesenchymal transition.

Mol Cancer 2017 01 17;16(1):12. Epub 2017 Jan 17.

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 85 Wujin Road, Shanghai, 200080, China.

Background: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression.

Methods: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGFβ pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC.

Results: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGFβ signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/Smad7/TGFβ in vitro and in vivo.

Conclusion: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGFβ signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12943-017-0585-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240405PMC
January 2017

miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation.

Cancer Lett 2017 03 30;389:11-22. Epub 2016 Dec 30.

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2016.12.033DOI Listing
March 2017

The chromatin-remodeling enzyme BRG1 promotes colon cancer progression via positive regulation of WNT3A.

Oncotarget 2016 Dec;7(52):86051-86063

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080,China.

In this study, we aimed to elucidate the clinical significance and underlying mechanisms of BRG1 in colon cancer. In the clinical analysis, overexpression of BRG1 correlates with colon cancer progression in two cohorts (n = 191 and n = 75). Kaplan-Meier survival analysis revealed that BRG1 is a prognosis predictor for overall survival (P < 0.001) and disease-free survival (P = 0.001). Knocking down BRG1 expression significantly suppressed the proliferation and invasion in colon cancer cells. The expression pattern of WNT3A is consistent with BRG1 in colon cancer tissues and WNT3A expression was inhibited in BRG1 knockdown cells. In addition, restoring WNT3A expression rescues the inhibition of cell proliferation and invasion induced by BRG1. In this study, we demonstrate that BRG1 may contribute to colon cancer progression through upregulating WNT3A expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349896PMC
December 2016

A comparative analysis and guidance for individualized chemotherapy of stage II and III colorectal cancer patients based on pathological markers.

Sci Rep 2016 11 15;6:37240. Epub 2016 Nov 15.

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.

Adjuvant chemotherapy is considered the standard of care for patients with colorectal cancer after curative resection. Although current guidelines provide clear instructions for chemotherapy for stage II high-risk and stage III colorectal cancer, it is insufficient to individualize therapy. We analyzed the outcomes of 902 patients with colorectal cancer treated with or without chemotherapy in our hospital. We found Chinese survival benefit for chemotherapy was consistent with current guidelines. Moreover, our data added to the evidence that chemotherapy might be used for elderly patients with stage II high-risk colorectal cancer. Pathological markers could predict response to individualize therapy in a convenient, fast and inexpensive way. We compared survivals of patients with stage II high-risk and stage III colorectal cancer with chemotherapy in different pathological markers expression, and furthermore used 458 colon adenocarcinoma samples from The Cancer Genome Atlas to verify our preliminary results. We confirmed TOPIIα, EGFR and P170 may be sufficiently predictive markers to individualize chemotherapy. FOLFOX was the optimal adjuvant chemotherapy for patients with stage II high-risk and stage III colorectal cancer when TOPIIα was positive or EGFR or P170 was negative.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep37240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109035PMC
November 2016

Downregulation of homeobox gene Barx2 increases gastric cancer proliferation and metastasis and predicts poor patient outcomes.

Oncotarget 2016 Sep;7(37):60593-60608

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.

Barx2 is a Bar family homeodomain transcription factor shown to play a critical role in cell adhesion and cytoskeleton remodeling, key processes in carcinogenesis and metastasis. Using quantitative real-time PCR, Western blotting, and immunohistochemistry, we found that Barx2 is expressed at lower levels in human gastric cancer (GC) tissues than in adjacent normal mucosa. In a multivariate analysis, Barx2 expression emerged as an independent prognostic factor for disease-free and overall survival. Kaplan-Meier survival analysis showed a trend toward even shorter overall survival in the patient group with Barx2-negative tumors, independent of advanced UICC stage and tumor relapse. Using in vitro and in vivo assays, we demonstrated that under normal conditions Barx2 inhibited GC cell proliferation and invasiveness through inhibition of the Wnt/β-catenin signaling pathway. These findings indicate that reduction or loss of Barx2 dis-inhibits GC cell proliferation and invasion, and that reduction in Barx2 could serve as an independent prognostic biomarker for poor outcome in GC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.11260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312404PMC
September 2016

1-Alpha, 25-dihydroxyvitamin D3 alters the pharmacokinetics of mycophenolic acid in renal transplant recipients by regulating two extrahepatic UDP-glucuronosyltransferases 1A8 and 1A10.

Transl Res 2016 12 19;178:54-62.e6. Epub 2016 Jul 19.

Department of General Surgery, Shanghai First People's Hospital, Medical College, Shanghai Jiaotong University, Shanghai, P. R. China. Electronic address:

Mycophenolic acid (MPA) is an important immunosuppressant broadly used in renal transplantation. However, the large inter-patient variability in mycophenolic acid (MPA) pharmacokinetics (PK) limits its use. We hypothesize that extrahepatic metabolism of MPA may have significant impact on MPA PK variability. Two intestinal UDP-glucuronosyltransferases 1A8 and 1A10 plays critical role in MPA metabolism. Both in silico and previous genome-wide analyses suggested that vitamin D (VD) may regulate intestinal UGT1A expression. We validated the VD response elements (VDREs) across the UGT1A locus with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The impact of 1-alpha,25-dihydroxyvitamin D3 (D3) on UGT1A8 and UGT1A10 transcription and on MPA glucuronidation was tested in human intestinal cell lines LS180, Caco-2 and HCT-116. The correlation between transcription levels of VD receptor (VDR) and the two UGT genes were examined in human normal colorectal tissue samples (n = 73). PK alterations of MPA following the parent drug, mycophenolate mofetil (MMF), and D3 treatment was assessed among renal transplant recipients (n = 10). Our ChIP assay validate three VDREs which were further demonstrated as transcriptional enhancers with the luciferase assays. D3 treatment significantly increased transcription of both UGT genes as well as MPA glucuronidation in cells. The VDR mRNA level was highly correlated with that of both UGT1A8 and UGT1A10 in human colorectal tissue. D3 treatment in patients led to about 40% reduction in both AUC and Cmax while over 70% elevation of total clearance of MPA. Our study suggested a significant regulatory role of VD on MPA metabolism and PK via modulating extrahepatic UGT activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trsl.2016.07.006DOI Listing
December 2016

Down-regulation of Barx2 predicts poor survival in colorectal cancer.

Biochem Biophys Res Commun 2016 09 22;478(1):67-73. Epub 2016 Jul 22.

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 85 Wujin Road, 200080 Shanghai, China; Department of Oncology and Department of Clinical and Experimental Medicine, Linkoping University, SE-581 85 Linkoping, Sweden. Electronic address:

Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, has an important role in controlling the expression of cell adhesion molecules and has been reported in an increasing array of tumor types except colorectal cancer (CRC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in CRC. First, we analyzed the expression of Barx2 in two independent public datasets from Oncomine. Subsequently, we evaluated Barx2 mRNA and protein expression by quantitative real-time PCR and western blotting, respectively. It was determined that Barx2 expression was lower in tumor tissues than in adjacent non-tumorous colorectal tissues of CRC patients, consistent with results from the public datasets. Subsequently, a tissue microarray containing 196 CRC specimens was evaluated for Barx2 expression by immunohistochemical staining. It was found that low expression of Barx2 significantly correlated with TNM stage, AJCC stage, differentiation, and relapse in patients with CRC. Patients with lower levels of Barx2 expression showed reduced disease-free survival and overall survival. Furthermore, a trend toward shorter overall survival in the patient group with Barx2-negative tumors independent of advanced AJCC stage and poor differentiation was determined by Kaplan-Meier survival analysis. Based on univariate and multivariate analyses, Barx2 expression was an independent prognostic factor for determining CRC prognosis. Taken together, low Barx2 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2016.07.091DOI Listing
September 2016

Metalloproteases meprin-ɑ (MEP1A) is a prognostic biomarker and promotes proliferation and invasion of colorectal cancer.

BMC Cancer 2016 07 4;16:383. Epub 2016 Jul 4.

Department of General Surgery, First People's Hospital, Shanghai Jiao Tong Univerisity, 85 Wujin Road, Shanghai, 200080, China.

Background: Meprin displays multiple functions in both health and disease, due in part to its broad proteolytic activity. In this report, we explored the clinical significance and functional relevance of the expression of meprin-ɑ (MEP1A) in colorectal cancer (CRC).

Methods: The mRNA and protein expression levels of MEP1A in tumor specimens obtained from CRC patients was determined by quantitative real-time PCR and Western blot assay and comparatively paired with adjacent mucosa that presented as normal tissue. ShRNA was used to knock-down MEP1A expression in CRC cell-lines and the effects of dampened expression of MEP1A on the proliferation and invasion were determined by colony formation assays, Cell Counting Kit-8 assays and matrigel invasion assays. Moreover, nude mouse xenograft models were designed to investigate the same effect in vivo. In order to determine whether MEP1A expression correlated with CRC clinicopathologic factors and survival, immunohistochemical staining of a tissue microarray containing 88 paired CRC specimens was performed.

Results: In CRC, enhanced expression of MEP1A was seen. Additionally, both in vitro and in vivo, CRC cellular proliferation and invasiveness was inhibited by dampened MEP1A expression. Several parameters were associated with enhanced MEP1A expression including tumor size (P = 0.023), staging of CRC by the American Joint Committee on Cancer (AJCC) (P = 0.024), and T (P = 0.032) and N stages (P = 0.001). Moreover, the expression of MEP1A is an independent prognostic factor for overall survival in CRC (HR 3.643; 95 % CI 0.305-5.842; P = 0.007).

Conclusion: MEP1A was not only found to be functionally important, but it might also serve as an important and unique indicator of patient prognosis and therapeutic targeting in CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-016-2460-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932728PMC
July 2016

High-level expression of P21-Cdc/Rac-activated kinase 7 is closely related to metastatic potential and poor prognosis of colon carcinoma.

Oncotarget 2016 Jul;7(29):46042-46055

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China.

P21 protein (Cdc42/Rac)-activated kinase 7 (PAK7) can promote neurite outgrowth, induce microtubule stabilization, and activate cell survival signaling pathways. PAK7 expression was found to increase with colon carcinoma progression, but the prognostic value, clinical significance, and underlying mechanisms have not been explored. In my study, the expression of PAK7 was up-related at both the transcriptional and the translational levels in colon tumors compared to that in adjacent normal colon tissue. Patients with PAK7-positive tumors had a lower rate of overall survival (OS) and metastasis-free survival (MFS) (log-rank test, P < 0.001). A Cox proportional hazards model showed that PAK7 expression was an independent prognostic factor for OS (hazard ration [HR], 2.08; 95% confidence interval [CI], 1.16-3.73; P = 0.004) and MFS (HR, 2.88; 95% CI, 1.53-5.42; P < 0.001) in patients with colon cancer. Patients with tumors that were over-expressing PAK7 experienced metastasis, and died within a significantly shorter time after surgery (P < 0.001). Knockdown of PAK7 by a specific short hairpin RNA (shRNA) significantly suppressed the progression of epithelial to mesechymal transition (EMT), migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. However, overexpression of PAK7 significantly promoted these processes. These findings indicate that aberrant PAK7 expression is associated with the occurrence of metastasis and poor clinical outcomes of human colon cancer by promoting the EMT, and the assessment of PAK7 expression might be helpful in predicting metastasis and prognostication for patients with colon cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.10017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216780PMC
July 2016

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4.

Oncotarget 2016 Jul;7(29):45199-45213

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known.

Results: miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients.

Methods: Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data.

Conclusions: miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.9900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216716PMC
July 2016

Decreased MALL expression negatively impacts colorectal cancer patient survival.

Oncotarget 2016 Apr;7(16):22911-27

Department of General Surgery, Shanghai First People's Hospital, Medical College, Shanghai Jiao Tong University, Shanghai, China.

The aim of the present study was to determine whether MALL expression is associated with colon cancer progression and patient survival. MALL mRNA expression was reduced in the tumor tissues of 70% of the colon cancer patients and 75% of the rectal cancer patients as compared to their normal tissues. MALL protein was also significantly reduced in the tumor tissues of colon cancer patients (P < 0.001). Increased LOH and methylation of MALL was observed in tumor tissues as compared to normal tissues. Reduced MALL expression was associated with vessin invasion, disease recurrence and metastasis or death (P ≤ 0.027). Furthermore, patients with MALL-negative tumors had significantly decreased overall survival (OS) and disease-free survival (DFS) (P < 0.008 and P < 0.011, respectively). Univariate analysis indicated that MALL expression was significantly associated with OS and DFS. Finally, overexpression of MALL suppressed HCT116 and SW480 cell proliferation and inhibited HCT116 migration. MALL may play a role in colorectal cancer progression as suppression of its expression in tumor tissues negatively impacts colorectal cancer patient survival. Further analyses are required to determine if reduced MALL expression is due to LOH and/or methylation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.8094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008411PMC
April 2016

DDA1 promotes stage IIB-IIC colon cancer progression by activating NFκB/CSN2/GSK-3β signaling.

Oncotarget 2016 Apr;7(15):19794-812

Department of General Surgery, Shanghai First People's Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Conventional high-recurrence risk factors are not sufficient to predict post-operative risk of tumor recurrence or sensitivity to 5-fluorouracil (5-FU)-based chemotherapy for stage II colon cancer. DDA1, an evolutionarily conserved gene located at 19p13.11, may be involved in the activation of nuclear factor kappaB (NFκB). This study aimed to investigate whether DDA1 contributes to tumorigenesis and progression of stage II colon cancer via activation of the NFκB pathway. We found that positive expression of DDA1 alone or in combination with p65 nuclear translocation correlated with increased risk of tumor recurrence in patients with stage IIB-IIC colon cancer. DDA1 overexpression in colon cancer lines promoted cell proliferation, facilitated cell cycle progression, inhibited 5-FU-induced apoptosis, enhanced invasion, and induced the epithelial-mesenchymal transition. Suppression of DDA1 inhibited tumor progression, and reduced tumor growth in vivo. We also demonstrated that DDA1-mediated tumor progression is associated with the activation of the NFκB/COP9 signalosome 2(CSN2)/glycogen synthase kinase3β (GSK3β) pathway. These results indicate that DDA1 promotes colon cancer progression through activation of NFκB/CSN2/GSK3β signaling. DDA1, together with NFκB activation status, may serve as a sensitive biomarker for tumor recurrence risk and prognosis in patients with stage IIB-IIC colon cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.7847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991419PMC
April 2016

Multi-slice computed tomography characteristics of solitary pulmonary ground-glass nodules: Differences between malignant and benign.

Thorac Cancer 2016 Jan 12;7(1):80-7. Epub 2015 Jun 12.

Department of Thoracic Surgery Shanghai First People's Hospital Shanghai China.

Background: Ground-glass nodules (GGNs), which are possible precursors of lung cancer, attract increasing attention. Many studies have attempted to identify the characteristic imaging features of GGNs for their qualitative diagnosis; however, the comprehension of GGNs remains controversial. We performed this study to identify imaging characteristics helpful to the differential diagnosis of solitary GGNs.

Methods: We retrospectively evaluated 112 solitary GGNs resected from 112 patients, pathologically examined after surgical resection. Imaging features of the GGNs, such as size, shape, a solid component, lobulation, spiculation, vascular convergence sign, pleural tag, and air cavity density, were assessed. Differences between malignant and benign nodules were analyzed using binary logistic regression analysis.

Results: Of the 112 GGNs, 82 were malignant and 30 were benign. A solid component, vascular convergence sign, and a larger diameter were risk factors for malignancy, with a sensitivity, specificity, and accuracy of 93.9%, 60.0%, and 84.8%, respectively. Lobulation, spiculation, air cavity densities, and pleural tags were also important indicators of malignancy, with positive predictive values of 93.5%, 83.3%, 91.7%, and 87.2%, respectively.

Conclusion: GGNs with a solid component, vascular convergence sign, and a larger diameter are highly suggestive of malignancy. The possibility of a neoplasm should also be considered in the case of GGNs that show lobulation, spiculation, air cavity densities, or pleural tags. To obtain a comprehensive and accurate analysis of the nodules, three-dimensional reconstruction is highly recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.12280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718137PMC
January 2016

Combined detection of preoperative serum CEA, CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients.

Int J Clin Exp Pathol 2015 1;8(11):14853-63. Epub 2015 Nov 1.

Department of General Surgery, First People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.

We assessed the prognostic significance of preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) levels in surgically treated colorectal cancer patients. The relationship of preoperative serum CEA, CA19-9 and CA242 levels with disease characteristics was investigated in 310 patients. Correlation between tumor markers was investigated using Pearson correlation test. Univariate and multivariate survival analyses were used to study the relationship between preoperative tumor markers and prognosis [disease free survival (DFS) and overall survival (OS)]. Kaplan-Meier analysis with log rank test was used to assess the impact of tumor marker levels on survival. Positive rate of preoperative serum CEA, CA19-9 and CA242 were 54.84%, 47.42% and 37.10%, respectively. High preoperative CEA level was associated with tumor size (P = 0.038), T stage (P < 0.001) and AJCC stage (P = 0.002). High preoperative CA19-9 level was associated with tumor AJCC stage (P = 0.023). Preoperative CA242 positively correlated with CEA (P < 0.001) and CA19-9 (P < 0.001). Combining the three markers was of independent prognostic value in CRC (HR = 2.532, 95% CI: 1.400-4.579, P = 0.002 for OS; and HR = 2.366, 95% CI: 1.334-4.196, P = 0.003 for DFS). Combined detection of preoperative serum CEA, CA19-9 and CA242 is of independent prognostic value for management of CRC patients treated surgically.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713601PMC
November 2016

Karyopherin alpha 2 is a novel prognostic marker and a potential therapeutic target for colon cancer.

J Exp Clin Cancer Res 2015 Dec 1;34:145. Epub 2015 Dec 1.

Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China.

Background: Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, plays a vital role in carcinogenesis. Yet its role in colon cancer is poorly characterized. We sought to clarify the clinical significance of its dysregulated expression in human colon tumor specimens.

Methods: We evaluated KPNA2 mRNA and protein expression by real-time polymerase chain reaction and Western blotting in 40 primary colon cancer tissues and paired adjacent normal colon mucosa specimens. KPNA2 protein expression in colon tissue microarray of tumor and normal tissue specimens and lymph node metastasis specimens obtained from 195 colon cancer patients were analyzed immunohistochemically. The effect of KPNA2 knockdown on carcinogenesis potential of human colon cancer cells was determined using Cell Counting Kit-8 (CCK8), colony formation, cell migration, and tumorigenesis in nude mice.

Results: KPNA2 was expressed at higher levels in colon tumors and lymph node metastasis specimens than in normal tissues. Patients with KPNA2-positive tumors were significantly correlated with the American Joint Committee on Cancer (AJCC) stage (p = 0.01), T-classification (p = 0.018), regional lymph node metastasis (p = 0.025), distant metastasis (p = 0.014), and differentiated degree (p = 0.001). KPNA2 was shown to be an independent prognostic indicator of disease-free survival (HR 1.681; 95 % CI: 1.170-2.416; p = 0.005) and overall survival (HR 2.770; 95 % CI: 1.314-5.837; p = 0.007) for patients with colon cancer. Knockdown of KPNA2 expression inhibited colon cancer cell proliferation, colony formation, and migration.

Conclusion: KPNA2 might play an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-015-0261-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665890PMC
December 2015
-->