Revealing gene clusters associated with the development of cholangiocarcinoma, based on a time series analysis

Wu,Jianyu; Xiao,Zhifu; Zhao,Xiulei; Wu,Xiangsong

doi:10.3892/mmr.2015.3216

Revealing gene clusters associated with the development of cholangiocarcinoma, based on a time series analysis

Authors:
- Jianyu Wu
- Zhifu Xiao
- Xiulei Zhao
- Xiangsong Wu
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Affiliations: Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of General Surgery, The Central Hospital of Cangzhou, Cangzhou, Hebei 061000, P.R. China
Published online on: January 16, 2015 https://doi.org/10.3892/mmr.2015.3216
Pages: 3481-3486

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Abstract

Cholangiocarcinoma (CC) is a rapidly lethal malignancy and currently is considered to be incurable. Biomarkers related to the development of CC remain unclear. The present study aimed to identify differentially expressed genes (DEGs) between normal tissue and intrahepatic CC, as well as specific gene expression patterns that changed together with the development of CC. By using a two‑way analysis of variance test, the biomarkers that could distinguish between normal tissue and intrahepatic CC dissected from different days were identified. A k‑means cluster method was used to identify gene clusters associated with the development of CC according to their changing expression pattern. Functional enrichment analysis was used to infer the function of each of the gene sets. A time series analysis was constructed to reveal gene signatures that were associated with the development of CC based on gene expression profile changes. Genes related to CC were shown to be involved in ‘mitochondrion’ and ‘focal adhesion’. Three interesting gene groups were identified by the k‑means cluster method. Gene clusters with a unique expression pattern are related with the development of CC. The data of this study will facilitate novel discoveries regarding the genetic study of CC by further work.

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1	Tsao JI, Nimura Y, Kamiya J, et al: Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience. Ann Surg. 232:166–174. 2000. View Article : Google Scholar : PubMed/NCBI
2	Nakeeb A, Pitt HA, Sohn TA, et al: Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg. 224:463–473. PubMed/NCBI
3	Rajagopalan V, Daines WP, Grossbard ML and Kozuch P: Gallbladder and biliary tract carcinoma: A comprehensive update, Part 1. Oncology (Williston Park). 18:889–896. 2004.
4	Weber SM, DeMatteo RP, Fong Y, Blumgart LH and Jarnagin WR: Staging laparoscopy in patients with extrahepatic biliary carcinoma. Analysis of 100 patients. Ann Surg. 235:392–399. 2002. View Article : Google Scholar : PubMed/NCBI
5	Callery MP, Strasberg SM, Doherty GM, Soper NJ and Norton JA: Staging laparoscopy with laparoscopic ultrasonography: optimizing resectability in hepatobiliary and pancreatic malignancy. J Am Coll Surg. 185:33–39. 1997. View Article : Google Scholar : PubMed/NCBI
6	Miyakawa S, Ishihara S, Horiguchi A, et al: Biliary tract cancer treatment: 5,584 results from the Biliary Tract Cancer Statistics Registry from 1998 to 2004 in Japan. J Hepatobiliary Pancreat Surg. 16:1–7. 2009. View Article : Google Scholar
7	Landis SH, Murray T, Bolden S and Wingo PA: Cancer statistics, 1998. CA Cancer J Clin. 48:6–29. 1998. View Article : Google Scholar : PubMed/NCBI
8	Patel T: Worldwide trends in mortality from biliary tract malignancies. BMC Cancer. 2:102002. View Article : Google Scholar : PubMed/NCBI
9	Burak K, Angulo P, Pasha TM, et al: Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 99:523–526. 2004. View Article : Google Scholar : PubMed/NCBI
10	Khorsandi SE, Salvans S, Zen Y, et al: Cholangiocarcinoma complicating recurrent primary sclerosing cholangitis after liver transplantation. Transpl Int. 24:e93–e96. 2011. View Article : Google Scholar : PubMed/NCBI
11	Kaya M, de Groen PC, Angulo P, et al: Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience. Am J Gastroenterol. 96:1164–1169. 2001. View Article : Google Scholar : PubMed/NCBI
12	Chaiyarit P, Sithithaworn P, Thuwajit C and Yongvanit P: Detection of salivary antibodies to crude antigens of Opisthorchis viverrini in opisthorchiasis and cholangiocarcinoma patients. Clin Oral Investig. 15:477–483. 2011. View Article : Google Scholar
13	Hughes NR, Pairojkul C, Royce SG, Clouston A and Bhathal PS: Liver fluke-associated and sporadic cholangiocarcinoma: an immunohistochemical study of bile duct, peribiliary gland and tumour cell phenotypes. J Clin Pathol. 59:1073–1078. 2006. View Article : Google Scholar : PubMed/NCBI
14	Shin HR, Lee CU, Park HJ, et al: Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea. Int J Epidemiol. 25:933–940. 1996. View Article : Google Scholar : PubMed/NCBI
15	Shaib YH, El-Serag HB, Davila JA, Morgan R and McGlynn KA: Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study. Gastroenterology. 128:620–626. 2005. View Article : Google Scholar : PubMed/NCBI
16	Sorensen HT, Friis S, Olsen JH, et al: Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark. Hepatology. 28:921–925. 1998. View Article : Google Scholar : PubMed/NCBI
17	Briggs CD, Neal CP, Mann CD, et al: Prognostic molecular markers in cholangiocarcinoma: a systematic review. Eur J Cancer. 45:33–47. 2009. View Article : Google Scholar
18	Storto PD, Saidman SL, Demetris AJ, et al: Chromosomal breakpoints in cholangiocarcinoma cell lines. Genes Chromosomes Cancer. 2:300–310. 1990. View Article : Google Scholar : PubMed/NCBI
19	Barrett T and Edgar R: Gene expression omnibus: microarray data storage, submission, retrieval, and analysis. Methods Enzymol. 411:352–369. 2006. View Article : Google Scholar : PubMed/NCBI
20	Gautier L, Cope L, Bolstad BM and Irizarry RA: affy - analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 20:307–315. 2004. View Article : Google Scholar : PubMed/NCBI
21	Hu J and He X: Enhanced quantile normalization of microarray data to reduce loss of information in gene expression profiles. Biometrics. 63:50–59. 2007. View Article : Google Scholar : PubMed/NCBI
22	Perneger T and Perrier A: Analysis of variance, part 1 (the t-test and ANOVA). Rev Mal Respir. 21:797–801. 2004.(In French). View Article : Google Scholar : PubMed/NCBI
23	Huang da W, Sherman BT, Tan Q, et al: DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 35:W169–W175. 2007. View Article : Google Scholar : PubMed/NCBI
24	Kanehisa M and Goto S: KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000. View Article : Google Scholar
25	Beauchaine TP and Beauchaine RJ 3rd: A comparison of maximum covariance and K-means cluster analysis in classifying cases into known taxon groups. Psychol Methods. 7:245–261. 2002. View Article : Google Scholar : PubMed/NCBI
26	Sirica AE: The role of cancer-associated myofibroblasts in intrahepatic cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 9:44–54. 2011. View Article : Google Scholar : PubMed/NCBI
27	Masyuk AI, Huang BQ, Ward CJ, et al: Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia. Am J Physiol Gastrointest Liver Physiol. 299:G990–G999. 2010. View Article : Google Scholar : PubMed/NCBI
28	Okaro AC, Fennell DA, Corbo M, Davidson BR and Cotter FE: Pk11195, a mitochondrial benzodiazepine receptor antagonist, reduces apoptosis threshold in Bcl-X(L) and Mcl-1 expressing human cholangiocarcinoma cells. Gut. 51:556–561. 2002. View Article : Google Scholar : PubMed/NCBI
29	Lamberts RR, Van Rijen MH, Sipkema P, et al: Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms. Am J Physiol Heart Circ Physiol. 283:H1515–H1522. 2002. View Article : Google Scholar : PubMed/NCBI
30	Nishino R, Honda M, Yamashita T, et al: Identification of novel candidate tumour marker genes for intrahepatic cholangiocarcinoma. J Hepatol. 49:207–216. 2008. View Article : Google Scholar : PubMed/NCBI
31	Nehls O, Gregor M and Klump B: Serum and bile markers for cholangiocarcinoma. Semin Liver Dis. 24:139–154. 2004. View Article : Google Scholar : PubMed/NCBI
32	Zhang K, Zhaos J, Liu X, et al: Activation of NF-B upregulates Snail and consequent repression of E-cadherin in cholangiocarcinoma cell invasion. Hepatogastroenterology. 58:1–7. 2011.PubMed/NCBI
33	Zhang KJ, Wang DS, Zhang SY, et al: The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma. J Exp Clin Cancer Res. 29:882010. View Article : Google Scholar : PubMed/NCBI
34	Techasen A, Namwat N, Loilome W, et al: Tumor necrosis factor-α (TNF-α) stimulates the epithelial-mesenchymal transition regulator Snail in cholangiocarcinoma. Med Oncol. 29:3083–3091. 2012. View Article : Google Scholar : PubMed/NCBI
35	Zabron A, Edwards RJ and Khan SA: The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer. Dis Model Mech. 6:281–292. 2013. View Article : Google Scholar : PubMed/NCBI
36	Larusso NF: Patients, cells, and organelles: the intersection of science and serendipity. Hepatology. 53:1417–1426. 2011. View Article : Google Scholar : PubMed/NCBI
37	Taniai M, Grambihler A, Higuchi H, et al: Mcl-1 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in human cholangiocarcinoma cells. Cancer Res. 64:3517–3524. 2004. View Article : Google Scholar : PubMed/NCBI
38	Schwock J, Dhani N and Hedley DW: Targeting focal adhesion kinase signaling in tumor growth and metastasis. Expert Opin Ther Targets. 14:77–94. 2010. View Article : Google Scholar
39	Fraley SI, Feng Y, Krishnamurthy R, et al: A distinctive role for focal adhesion proteins in three-dimensional cell motility. Nat Cell Biol. 12:598–604. 2010. View Article : Google Scholar : PubMed/NCBI
40	Drukman S and Kavallaris M: Microtubule alterations and resistance to tubulin-binding agents (review). Int J Oncol. 21:621–628. 2002.PubMed/NCBI
41	Pokorný J, Vedruccio C, Cifra M and Kučera O: Cancer physics: diagnostics based on damped cellular elastoelectrical vibrations in microtubules. Eur Biophys J. 40:747–759. 2011. View Article : Google Scholar : PubMed/NCBI