Skip to main content
Top
Published in: Diagnostic Pathology 1/2014

Open Access 01-12-2014 | Research

Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma

Authors: Zhu-qing Zhang, Hua Meng, Nan Wang, Li-na Liang, Li-na Liu, Shu-ming Lu, Yong Luan

Published in: Diagnostic Pathology | Issue 1/2014

Login to get access

Abstract

Background

Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis or monitor postoperative recurrence and to give adequate treatment for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the application of miR-143 and miR-215 in the diagnosis of HCC.

Methods

A total of 340 serum samples (127 samples from controls, 118 samples from hepatitis and 95 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-143 and miR-215) were detected by probe-based stem-loop quantitative reverse-transcriptase PCR (RT-qPCR) in controls, hepatitis and HCC patients. Besides, the relationship between miR-143 and miR-215 levels and clinical and pathological factors was explored.

Results

We found that the expression of serum miR-215 was distinctly increased in chronic hepatitis compared with controls (mean ± SD: 6.79 ± 0.72 vs. 3.46 ± 0.37, P < 0.001 and mean ± SD: 8.38 ± 0.87 vs. 3.46 ± 0.37, P < 0.001). In addition, we conduct ROC analyses to detect the potential application of miR-143 and miR-215 in the diagnosis of chronic hepatitis and HCC. Our results showed that miR-143 and miR-215 might be a potential biomarker for the hepatitis and HCC.

Conclusions

In conclusion, the expression of miR-143 and miR-215 in serum were significantly up-regulated in patients with chronic hepatitis and HCC. Due to its reasonable sensitivity and specificity for both diseases, miR-143 and miR-215 could be as potential circulating biomarkers.

Virtual Slides

Literature
1.
go back to reference Milanizadeh S, Khanyaghma M, Haghighi MM, Mohebbi S, Damavand B, Almasi S, Azimzadeh P, Zali M: Molecular analysis of imperative polymorphisms of MLH1 gene in sporadic colorectal cancer. Cancer Biomark. 2013, 13: 427-432.PubMed Milanizadeh S, Khanyaghma M, Haghighi MM, Mohebbi S, Damavand B, Almasi S, Azimzadeh P, Zali M: Molecular analysis of imperative polymorphisms of MLH1 gene in sporadic colorectal cancer. Cancer Biomark. 2013, 13: 427-432.PubMed
2.
go back to reference Abdel-Wahab M, El-Ghawalby N, Mostafa M, Sultan A, El-Sadany M, Fathy O, Salah T, Ezzat F: Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center. Hepatogastroenterology. 2007, 54: 157-162.PubMed Abdel-Wahab M, El-Ghawalby N, Mostafa M, Sultan A, El-Sadany M, Fathy O, Salah T, Ezzat F: Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center. Hepatogastroenterology. 2007, 54: 157-162.PubMed
3.
go back to reference Bao YX, Cao Q, Yang Y, Mao R, Xiao L, Zhang H, Zhao HR, Wen H: Expression and prognostic significance of Golgiglycoprotein73 (GP73) with Epithelial-mesenchymal transition (EMT) related molecules in Hepatocellular Carcinoma (HCC). Diagn Pathol. 2013, 8: 197-PubMedPubMedCentralCrossRef Bao YX, Cao Q, Yang Y, Mao R, Xiao L, Zhang H, Zhao HR, Wen H: Expression and prognostic significance of Golgiglycoprotein73 (GP73) with Epithelial-mesenchymal transition (EMT) related molecules in Hepatocellular Carcinoma (HCC). Diagn Pathol. 2013, 8: 197-PubMedPubMedCentralCrossRef
4.
go back to reference Kojiro M, Kawabata K, Kawano Y, Shirai F, Takemoto N, Nakashima T: Hepatocellular carcinoma presenting as intrabile duct tumor growth: a clinicopathologic study of 24 cases. Cancer. 1982, 49: 2144-2147.PubMedCrossRef Kojiro M, Kawabata K, Kawano Y, Shirai F, Takemoto N, Nakashima T: Hepatocellular carcinoma presenting as intrabile duct tumor growth: a clinicopathologic study of 24 cases. Cancer. 1982, 49: 2144-2147.PubMedCrossRef
5.
go back to reference Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA: Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. Cancer Biomark. 2007, 3: 79-87.PubMed Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA: Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. Cancer Biomark. 2007, 3: 79-87.PubMed
6.
go back to reference Chen MH, Jan YH, Chang PM, Chuang YJ, Yeh YC, Lei HJ, Hsiao M, Huang SF, Huang CY, Chau GY: Expression of GOLM1 correlates with prognosis in human hepatocellular carcinoma. Ann Surg Oncol. 2013, 20 (Suppl 3): S616-S624.PubMedCrossRef Chen MH, Jan YH, Chang PM, Chuang YJ, Yeh YC, Lei HJ, Hsiao M, Huang SF, Huang CY, Chau GY: Expression of GOLM1 correlates with prognosis in human hepatocellular carcinoma. Ann Surg Oncol. 2013, 20 (Suppl 3): S616-S624.PubMedCrossRef
7.
go back to reference Dogan E, Yalcin S, Koca D, Olmez A: Clinicopathological characteristics of hepatocellular carcinoma in Turkey. Asian Pac J Cancer Prev. 2012, 13: 2985-2990.PubMedCrossRef Dogan E, Yalcin S, Koca D, Olmez A: Clinicopathological characteristics of hepatocellular carcinoma in Turkey. Asian Pac J Cancer Prev. 2012, 13: 2985-2990.PubMedCrossRef
8.
go back to reference Huang J, Deng Q, Wang Q, Li KY, Dai JH, Li N, Zhu ZD, Zhou B, Liu XY, Liu RF, Fei QL, Chen H, Cai B, Xiao HS, Qin LX, Han ZG: Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. Nat Genet. 2012, 44: 1117-1121.PubMedCrossRef Huang J, Deng Q, Wang Q, Li KY, Dai JH, Li N, Zhu ZD, Zhou B, Liu XY, Liu RF, Fei QL, Chen H, Cai B, Xiao HS, Qin LX, Han ZG: Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. Nat Genet. 2012, 44: 1117-1121.PubMedCrossRef
9.
go back to reference Zhou G, Chiu D, Qin D, Niu L, Cai J, He L, Tan D, Xu K: Expression of CD44v6 and integrin-beta1 for the prognosis evaluation of pancreatic cancer patients after cryosurgery. Diagn Pathol. 2013, 8: 146-PubMedPubMedCentralCrossRef Zhou G, Chiu D, Qin D, Niu L, Cai J, He L, Tan D, Xu K: Expression of CD44v6 and integrin-beta1 for the prognosis evaluation of pancreatic cancer patients after cryosurgery. Diagn Pathol. 2013, 8: 146-PubMedPubMedCentralCrossRef
10.
go back to reference Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 2013, 495: 384-388.PubMedCrossRef Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 2013, 495: 384-388.PubMedCrossRef
11.
go back to reference Su ZX, Zhao J, Rong ZH, Geng WM, Wu YG, Qin CK: Upregulation of microRNA-25 associates with prognosis in hepatocellular carcinoma. Diagn Pathol. 2014, 9: 47-PubMedPubMedCentralCrossRef Su ZX, Zhao J, Rong ZH, Geng WM, Wu YG, Qin CK: Upregulation of microRNA-25 associates with prognosis in hepatocellular carcinoma. Diagn Pathol. 2014, 9: 47-PubMedPubMedCentralCrossRef
12.
14.
go back to reference Liu F, Xiong Y, Zhao Y, Tao L, Zhang Z, Zhang H, Liu Y, Feng G, Li B, He L, Ma J, Qin S, Yang Y: Identification of aberrant microRNA expression pattern in pediatric gliomas by microarray. Diagn Pathol. 2013, 8: 158-PubMedPubMedCentralCrossRef Liu F, Xiong Y, Zhao Y, Tao L, Zhang Z, Zhang H, Liu Y, Feng G, Li B, He L, Ma J, Qin S, Yang Y: Identification of aberrant microRNA expression pattern in pediatric gliomas by microarray. Diagn Pathol. 2013, 8: 158-PubMedPubMedCentralCrossRef
15.
go back to reference Wang W, Li F, Zhang Y, Tu Y, Yang Q, Gao X: Reduced expression of miR-22 in gastric cancer is related to clinicopathologic characteristics or patient prognosis. Diagn Pathol. 2013, 8: 102-PubMedPubMedCentralCrossRef Wang W, Li F, Zhang Y, Tu Y, Yang Q, Gao X: Reduced expression of miR-22 in gastric cancer is related to clinicopathologic characteristics or patient prognosis. Diagn Pathol. 2013, 8: 102-PubMedPubMedCentralCrossRef
16.
go back to reference Li Y, Chen L, Chan TH, Guan XY: Hepatocellular carcinoma: transcriptome diversity regulated by RNA editing. Int J Biochem Cell Biol. 2013, 45: 1843-1848.PubMedCrossRef Li Y, Chen L, Chan TH, Guan XY: Hepatocellular carcinoma: transcriptome diversity regulated by RNA editing. Int J Biochem Cell Biol. 2013, 45: 1843-1848.PubMedCrossRef
17.
go back to reference Ronald JA, Katzenberg R, Nielsen CH, Jae HJ, Hofmann LV, Gambhir SS: MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma. Gene Ther. 2013, 20: 1006-1013.PubMedCrossRef Ronald JA, Katzenberg R, Nielsen CH, Jae HJ, Hofmann LV, Gambhir SS: MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma. Gene Ther. 2013, 20: 1006-1013.PubMedCrossRef
18.
go back to reference Luo J, Chen M, Huang H, Yuan T, Zhang M, Zhang K, Deng S: Circulating microRNA-122a as a diagnostic marker for hepatocellular carcinoma. Onco Targets Ther. 2013, 6: 577-583.PubMedPubMedCentral Luo J, Chen M, Huang H, Yuan T, Zhang M, Zhang K, Deng S: Circulating microRNA-122a as a diagnostic marker for hepatocellular carcinoma. Onco Targets Ther. 2013, 6: 577-583.PubMedPubMedCentral
19.
go back to reference Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, Poon RT, Gao C, Luk JM: Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012, 2: e000825-PubMedPubMedCentralCrossRef Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, Poon RT, Gao C, Luk JM: Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012, 2: e000825-PubMedPubMedCentralCrossRef
20.
go back to reference Cui M, Xiao Z, Sun B, Wang Y, Zheng M, Ye L, Zhang X: Involvement of cholesterol in hepatitis B virus X protein-induced abnormal lipid metabolism of hepatoma cells via up-regulating miR-205-targeted ACSL4. Biochem Biophys Res Commun. 2014, 445: 651-655.PubMedCrossRef Cui M, Xiao Z, Sun B, Wang Y, Zheng M, Ye L, Zhang X: Involvement of cholesterol in hepatitis B virus X protein-induced abnormal lipid metabolism of hepatoma cells via up-regulating miR-205-targeted ACSL4. Biochem Biophys Res Commun. 2014, 445: 651-655.PubMedCrossRef
21.
go back to reference Gyugos M, Lendvai G, Kenessey I, Schlachter K, Halasz J, Nagy P, Garami M, Jakab Z, Schaff Z, Kiss A: MicroRNA expression might predict prognosis of epithelial hepatoblastoma. Virchows Arch. 2014, 464: 419-427.PubMedCrossRef Gyugos M, Lendvai G, Kenessey I, Schlachter K, Halasz J, Nagy P, Garami M, Jakab Z, Schaff Z, Kiss A: MicroRNA expression might predict prognosis of epithelial hepatoblastoma. Virchows Arch. 2014, 464: 419-427.PubMedCrossRef
22.
go back to reference Li J, Shi W, Gao Y, Yang B, Jing X, Shan S, Wang Y, Du Z: Analysis of microRNA expression profiles in human hepatitis B virus-related hepatocellular carcinoma. Clin Lab. 2013, 59: 1009-1015.PubMed Li J, Shi W, Gao Y, Yang B, Jing X, Shan S, Wang Y, Du Z: Analysis of microRNA expression profiles in human hepatitis B virus-related hepatocellular carcinoma. Clin Lab. 2013, 59: 1009-1015.PubMed
23.
go back to reference Xiao F, Zhang W, Zhou L, Xie H, Xing C, Ding S, Chen K, Zheng S: microRNA-200a is an independent prognostic factor of hepatocellular carcinoma and induces cell cycle arrest by targeting CDK6. Oncol Rep. 2013, 30: 2203-2210.PubMed Xiao F, Zhang W, Zhou L, Xie H, Xing C, Ding S, Chen K, Zheng S: microRNA-200a is an independent prognostic factor of hepatocellular carcinoma and induces cell cycle arrest by targeting CDK6. Oncol Rep. 2013, 30: 2203-2210.PubMed
24.
go back to reference Yu L, Ding GF, He C, Sun L, Jiang Y, Zhu L: MicroRNA-424 is down-regulated in Hepatocellular Carcinoma and suppresses cell migration and invasion through c-Myb. PLoS One. 2014, 9: e91661-PubMedPubMedCentralCrossRef Yu L, Ding GF, He C, Sun L, Jiang Y, Zhu L: MicroRNA-424 is down-regulated in Hepatocellular Carcinoma and suppresses cell migration and invasion through c-Myb. PLoS One. 2014, 9: e91661-PubMedPubMedCentralCrossRef
25.
go back to reference Wang L, Yao M, Dong Z, Zhang Y, Yao D: Circulating specific biomarkers in diagnosis of hepatocellular carcinoma and its metastasis monitoring. Tumour Biol. 2014, 35: 9-20.PubMedPubMedCentralCrossRef Wang L, Yao M, Dong Z, Zhang Y, Yao D: Circulating specific biomarkers in diagnosis of hepatocellular carcinoma and its metastasis monitoring. Tumour Biol. 2014, 35: 9-20.PubMedPubMedCentralCrossRef
26.
go back to reference Yang Y, Gu X, Zhou M, Xiang J, Chen Z: Serum microRNAs: a new diagnostic method for colorectal cancer. Biomed Rep. 2013, 1: 495-498.PubMedPubMedCentral Yang Y, Gu X, Zhou M, Xiang J, Chen Z: Serum microRNAs: a new diagnostic method for colorectal cancer. Biomed Rep. 2013, 1: 495-498.PubMedPubMedCentral
27.
go back to reference Sun L, Hu J, Xiong W, Chen X, Li H, Jie S: MicroRNA expression profiles of circulating microvesicles in hepatocellular carcinoma. Acta Gastroenterol Belg. 2013, 76: 386-392.PubMed Sun L, Hu J, Xiong W, Chen X, Li H, Jie S: MicroRNA expression profiles of circulating microvesicles in hepatocellular carcinoma. Acta Gastroenterol Belg. 2013, 76: 386-392.PubMed
28.
go back to reference Fu Y, Wei X, Tang C, Li J, Liu R, Shen A, Wu Z: Circulating microRNA-101 as a potential biomarker for hepatitis B virus-related hepatocellular carcinoma. Oncol Lett. 2013, 6: 1811-1815.PubMedPubMedCentral Fu Y, Wei X, Tang C, Li J, Liu R, Shen A, Wu Z: Circulating microRNA-101 as a potential biomarker for hepatitis B virus-related hepatocellular carcinoma. Oncol Lett. 2013, 6: 1811-1815.PubMedPubMedCentral
29.
go back to reference Ng EK, Li R, Shin VY, Siu JM, Ma ES, Kwong A: MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. Tumour Biol. 2014, 35: 2591-2598.PubMedCrossRef Ng EK, Li R, Shin VY, Siu JM, Ma ES, Kwong A: MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. Tumour Biol. 2014, 35: 2591-2598.PubMedCrossRef
30.
go back to reference Naito Y, Sakamoto N, Oue N, Yashiro M, Sentani K, Yanagihara K, Hirakawa K, Yasui W: MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer. Cancer Sci. 2014, 105: 228-235.PubMedPubMedCentralCrossRef Naito Y, Sakamoto N, Oue N, Yashiro M, Sentani K, Yanagihara K, Hirakawa K, Yasui W: MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer. Cancer Sci. 2014, 105: 228-235.PubMedPubMedCentralCrossRef
31.
go back to reference Schee K, Lorenz S, Worren MM, Gunther CC, Holden M, Hovig E, Fodstad O, Meza-Zepeda LA, Flatmark K: Deep sequencing the MicroRNA Transcriptome in Colorectal Cancer. PLoS One. 2013, 8: e66165-PubMedPubMedCentralCrossRef Schee K, Lorenz S, Worren MM, Gunther CC, Holden M, Hovig E, Fodstad O, Meza-Zepeda LA, Flatmark K: Deep sequencing the MicroRNA Transcriptome in Colorectal Cancer. PLoS One. 2013, 8: e66165-PubMedPubMedCentralCrossRef
32.
go back to reference Liu SG, Qin XG, Zhao BS, Qi B, Yao WJ, Wang TY, Li HC, Wu XN: Differential expression of miRNAs in esophageal cancer tissue. Oncol Lett. 2013, 5: 1639-1642.PubMedPubMedCentral Liu SG, Qin XG, Zhao BS, Qi B, Yao WJ, Wang TY, Li HC, Wu XN: Differential expression of miRNAs in esophageal cancer tissue. Oncol Lett. 2013, 5: 1639-1642.PubMedPubMedCentral
33.
go back to reference Masamune A, Nakano E, Hamada S, Takikawa T, Yoshida N, Shimosegawa T: Alteration of the microRNA expression profile during the activation of pancreatic stellate cells. Scand J Gastroenterol. 2014, 49: 323-331.PubMedCrossRef Masamune A, Nakano E, Hamada S, Takikawa T, Yoshida N, Shimosegawa T: Alteration of the microRNA expression profile during the activation of pancreatic stellate cells. Scand J Gastroenterol. 2014, 49: 323-331.PubMedCrossRef
34.
go back to reference Zhang X, Liu S, Hu T, He Y, Sun S: Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology. 2009, 50: 490-499.PubMedCrossRef Zhang X, Liu S, Hu T, He Y, Sun S: Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology. 2009, 50: 490-499.PubMedCrossRef
35.
go back to reference Senanayake U, Das S, Vesely P, Alzoughbi W, Frohlich LF, Chowdhury P, Leuschner I, Hoefler G, Guertl B: miR-192, miR-194, miR-215, miR-200c and miR-141 are downregulated and their common target ACVR2B is strongly expressed in renal childhood neoplasms. Carcinogenesis. 2012, 33: 1014-1021.PubMedCrossRef Senanayake U, Das S, Vesely P, Alzoughbi W, Frohlich LF, Chowdhury P, Leuschner I, Hoefler G, Guertl B: miR-192, miR-194, miR-215, miR-200c and miR-141 are downregulated and their common target ACVR2B is strongly expressed in renal childhood neoplasms. Carcinogenesis. 2012, 33: 1014-1021.PubMedCrossRef
36.
go back to reference White NM, Khella HW, Grigull J, Adzovic S, Youssef YM, Honey RJ, Stewart R, Pace KT, Bjarnason GA, Jewett MA, Evans AJ, Gabril M, Yousef GM: miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215. Br J Cancer. 2011, 105: 1741-1749.PubMedPubMedCentralCrossRef White NM, Khella HW, Grigull J, Adzovic S, Youssef YM, Honey RJ, Stewart R, Pace KT, Bjarnason GA, Jewett MA, Evans AJ, Gabril M, Yousef GM: miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215. Br J Cancer. 2011, 105: 1741-1749.PubMedPubMedCentralCrossRef
37.
go back to reference Gui J, Tian Y, Wen X, Zhang W, Zhang P, Gao J, Run W, Tian L, Jia X, Gao Y: Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin Sci (Lond). 2011, 120: 183-193.CrossRef Gui J, Tian Y, Wen X, Zhang W, Zhang P, Gao J, Run W, Tian L, Jia X, Gao Y: Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin Sci (Lond). 2011, 120: 183-193.CrossRef
38.
go back to reference Ishida H, Tatsumi T, Hosui A, Nawa T, Kodama T, Shimizu S, Hikita H, Hiramatsu N, Kanto T, Hayashi N, Takehara T: Alterations in microRNA expression profile in HCV-infected hepatoma cells: involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway. Biochem Biophys Res Commun. 2011, 412: 92-97.PubMedCrossRef Ishida H, Tatsumi T, Hosui A, Nawa T, Kodama T, Shimizu S, Hikita H, Hiramatsu N, Kanto T, Hayashi N, Takehara T: Alterations in microRNA expression profile in HCV-infected hepatoma cells: involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway. Biochem Biophys Res Commun. 2011, 412: 92-97.PubMedCrossRef
39.
go back to reference Chen Q, Ge X, Zhang Y, Xia H, Yuan D, Tang Q, Chen L, Pang X, Leng W, Bi F: Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer. Oncol Rep. 2014, 31: 1863-1870.PubMed Chen Q, Ge X, Zhang Y, Xia H, Yuan D, Tang Q, Chen L, Pang X, Leng W, Bi F: Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer. Oncol Rep. 2014, 31: 1863-1870.PubMed
Metadata
Title
Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma
Authors
Zhu-qing Zhang
Hua Meng
Nan Wang
Li-na Liang
Li-na Liu
Shu-ming Lu
Yong Luan
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2014
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-9-135

Other articles of this Issue 1/2014

Diagnostic Pathology 1/2014 Go to the issue