Transcriptome profiling of cancer tissues in Chinese patients with gastric cancer by high-throughput sequencing

Tian,Peiying; Liang,Chunli

doi:10.3892/ol.2017.7548

Transcriptome profiling of cancer tissues in Chinese patients with gastric cancer by high-throughput sequencing

Authors:
- Peiying Tian
- Chunli Liang
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Affiliations: Department of Gastroenterology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai 201399, P.R. China, Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
Published online on: December 8, 2017 https://doi.org/10.3892/ol.2017.7548
Pages: 2057-2064
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-associated mortality worldwide. Therefore, there is a requirement to identify sufficiently sensitive biomarkers for GC. Genome-wide screening of transcriptome dysregulation among cancerous and normal tissues may provide insights into the underlying molecular mechanisms of GC initiation and progression. At present, high-throughput sequencing techniques have begun to innovate biomedical studies. The RNA-seq method has become an advanced approach in medical studies; it is capable of the accurate detection of gene expression levels. The present study used RNA-seq to evaluate the transcriptional changes between tumor and matched normal samples, and these changes were confirmed by differentially expressed genes in larger samples using the results of sequencing. In total, the upregulation of 28 mRNAs and downregulation of 22 mRNAs between cancerous and normal tissue samples were identified. Subsequently, five differentially expressed genes were selected to verify in large samples and cadherin-1 (CDH1) was selected to detect protein expression levels. The results revealed that CDH1, cyclooxygenase-2 and matrix metalloproteinase genes had significantly higher expression levels, whereas the expression levels of dermatopontin and transforming growth factor β receptor 2 were decreased in GC samples. In particular, CDH1 demonstrated a 36-fold higher expression level in cancer tissues. The western blotting results also revealed high CDH1 expression levels in the validation cohorts. Furthermore, these genes are highly enriched in certain gene ontology categories, including the digestive system process, secretion and digestion. The present study provided a preliminary survey of the transcriptome of Chinese patients with GC, which may improve the detection of aberrant gene expression in GC and the understanding of the mechanisms of tumorigenesis.

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1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
2	Patel SA: The inferior vena cava (IVC) syndrome as the initial manifestation of newly diagnosed gastric adenocarcinoma: A case report. J Med Case Rep. 9:2042015. View Article : Google Scholar : PubMed/NCBI
3	Du T, Zhang B, Zhang S, Jiang X, Zheng P, Li J, Yan M, Zhu Z and Liu B: Decreased expression of long non-coding RNA WT1-AS promotes cell proliferation and invasion in gastric cancer. Biochim Biophys Acta. 1862:12–19. 2016. View Article : Google Scholar : PubMed/NCBI
4	Yao K, Nagahama T, Matsui T and Iwashita A: Detection and characterization of early gastric cancer for curative endoscopic submucosal dissection. Dig Endosc. 25 Suppl 1:S44–S54. 2013. View Article : Google Scholar
5	Amorim I, Smet A, Alves O, Teixeira S, Saraiva AL, Taulescu M, Reis C, Haesebrouck F and Gärtner F: Presence and significance of Helicobacter spp. in the gastric mucosa of Portuguese dogs. Gut Pathog. 7:122015. View Article : Google Scholar : PubMed/NCBI
6	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
7	Delaunoit T: Latest developments and emerging treatment options in the management of stomach cancer. Cancer Manag Res. 3:257–266. 2011. View Article : Google Scholar : PubMed/NCBI
8	Yegin EG, Kani T, Banzragch M, Kalayci C, Bicakci E and Duman DG: Survival in patients with hypoechoic muscularis propria lesions suggestive of gastrointestinal stromal tumors in gastric wall. Acta Gastroenterol Belg. 78:12–17. 2015.PubMed/NCBI
9	Printz C: High-throughput sequencing detects signs of cancer recurrence. Cancer. 118:40972012. View Article : Google Scholar
10	Conley A, Minciacchi VR, Lee DH, Knudsen BS, Karlan BY, Citrigno L, Viglietto G, Tewari M, Freeman MR, Demichelis F and Di Vizio D: High-throughput sequencing of two populations of extracellular vesicles provides an mRNA signature that can be detected in the circulation of breast cancer patients. RNA Biol. 14:305–316. 2017. View Article : Google Scholar : PubMed/NCBI
11	Dallol A, Buhmeida A, Al-Ahwal MS, Al-Maghrabi J, Bajouh O, Al-Khayyat S, Alam R, Abusanad A, Turki R, Elaimi A, et al: Clinical significance of frequent somatic mutations detected by high-throughput targeted sequencing in archived colorectal cancer samples. J Transl Med. 14:1182016. View Article : Google Scholar : PubMed/NCBI
12	Shaheen MF and Barrette P: Successful endoscopic management of gastric perforation caused by ingesting a sharp chicken bone. Int J Surg Case Rep. 9:12–14. 2015. View Article : Google Scholar : PubMed/NCBI
13	Bonfrate L, Grattagliano I, Palasciano G and Portincasa P: Dynamic carbon 13 breath tests for the study of liver function and gastric emptying. Gastroenterol Rep (Oxf). 3:12–21. 2015. View Article : Google Scholar : PubMed/NCBI
14	Luo YH, Liang L, He RQ, Wen DY, Deng GF, Yang H, He Y, Ma W, Cai XY, Chen JQ and Chen G: RNA-sequencing investigation identifies an effective risk score generated by three novel lncRNAs for the survival of papillary thyroid cancer patients. Oncotarget. 8:74139–74158. 2017.PubMed/NCBI
15	Tichá V, Jansa P and Tichý M: Retrospective study of gastric cancer on the basis of Lauren's classification criteria. Acta Univ Palacki Olomuc Fac Med. 120:193–198. 1988.PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Chen QH, Deng W, Li XW, Liu XF, Wang JM, Wang LF, Xiao N, He Q, Wang YP and Fan YM: Novel CDH1 germline mutations identified in Chinese gastric cancer patients. World J Gastroenterol. 19:909–916. 2013. View Article : Google Scholar : PubMed/NCBI
18	Garziera M, Canzonieri V, Cannizzaro R, Geremia S, Caggiari L, De Zorzi M, Maiero S, Orzes E, Perin T, Zanussi S, et al: Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer. PloS One. 8:e770352013. View Article : Google Scholar : PubMed/NCBI
19	Garziera M, De Re V, Geremia S, Seruca R, Figueiredo J, Melo S, Simões-Correia J, Caggiari L, De Zorzi M, Canzonieri V, et al: A novel CDH1 germline missense mutation in a sporadic gastric cancer patient in north-east of Italy. Clin Exp Med. 13:149–157. 2013. View Article : Google Scholar : PubMed/NCBI
20	Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, Schrader KA, Schaeffer DF, Shumansky K, Zogopoulos G, et al: Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol. 1:23–32. 2015. View Article : Google Scholar : PubMed/NCBI
21	de Campos EC, Ribeiro S, Higashi R, Manfredini R, Kfouri D and Cavalcanti TC: Hereditary diffuse gastric cancer: laparoscopic surgical approach associated to rare mutattion of CDH1 gene. Arq Bras Cir Dig. 28:149–151. 2015.(In English, Portuguese). View Article : Google Scholar : PubMed/NCBI
22	van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, Sijmons R, Aalfs CM, Ausems MG, Gómez García EB, et al: Accuracy of hereditary diffuse gastric cancer testing criteria and outcomes in patients with a germline mutation in CDH1. Gastroenterology. 149:897–906.e19. 2015. View Article : Google Scholar : PubMed/NCBI
23	Benusiglio PR, Colas C, Rouleau E, Uhrhammer N, Romero P, Remenieras A, Moretta J, Wang Q, De Pauw A, Buecher B, et al: Hereditary diffuse gastric cancer syndrome: Improved performances of the 2015 testing criteria for the identification of probands with a CDH1 germline mutation. J Med Genet. 52:563–565. 2015. View Article : Google Scholar : PubMed/NCBI
24	Lajus TB and Sales RM: CDH1 germ-line missense mutation identified by multigene sequencing in a family with no history of diffuse gastric cancer. Gene. 568:215–219. 2015. View Article : Google Scholar : PubMed/NCBI
25	Lynch HT and Lynch JF: Hereditary diffuse gastric cancer: lifesaving total gastrectomy for CDH1 mutation carriers. J Med Genet. 47:433–435. 2010. View Article : Google Scholar : PubMed/NCBI
26	Matsukuma KE, Mullins FM, Dietz L, Zehnder JL, Ford JM, Chun NM and Schrijver I: Hereditary diffuse gastric cancer due to a previously undescribed CDH1 splice site mutation. Hum Pathol. 41:1200–1203. 2010. View Article : Google Scholar : PubMed/NCBI
27	Pinheiro H, Bordeira-Carriço R, Seixas S, Carvalho J, Senz J, Oliveira P, Inácio P, Gusmão L, Rocha J, Huntsman D, et al: Allele-specific CDH1 downregulation and hereditary diffuse gastric cancer. Hum Mol Genet. 19:943–952. 2010. View Article : Google Scholar : PubMed/NCBI
28	Chen B, Zhou Y, Yang P, Liu L, Qin XP and Wu XT: CDH1-160C>A gene polymorphism is an ethnicity-dependent risk factor for gastric cancer. Cytokine. 55:266–273. 2011. View Article : Google Scholar : PubMed/NCBI
29	Chen Y, Kingham K, Ford JM, Rosing J, Van Dam J, Jeffrey RB, Longacre TA, Chun N, Kurian A and Norton JA: A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer. Ann Surg Oncol. 18:2594–2598. 2011. View Article : Google Scholar : PubMed/NCBI
30	Zhang P, Luo HS, Li M and Tan SY: Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2. Onco Targets Ther. 8:845–854. 2015. View Article : Google Scholar : PubMed/NCBI
31	Yu F, Li K, Chen S, Liu Y and Li Y: Pseudolaric acid B circumvents multidrug resistance phenotype in human gastric cancer SGC7901/ADR cells by downregulating Cox-2 and P-gp expression. Cell Biochem Biophys. 71:119–126. 2015. View Article : Google Scholar : PubMed/NCBI
32	Bai YN, Zhang P, Li L, Wang SL, Yao NL, Zhang RS, Liu Z, Yan D, Zhu YL, Ma JZ, et al: Effect of jianpi tongluo jiedu recipe on expression levels of COX-2, NF-kappaBp65, and Bcl-2 in gastric mucosa of patients with precancerous lesions of gastric cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi. 35:167–173. 2015.(In Chinese). PubMed/NCBI
33	Aziz F, Yang X, Wang X and Yan Q: Anti-LeY antibody enhances therapeutic efficacy of celecoxib against gastric cancer by downregulation of MAPKs/COX-2 signaling pathway: Correlation with clinical study. J Cancer Res Clin Oncol. 141:1221–1235. 2015. View Article : Google Scholar : PubMed/NCBI
34	Wang Z, Chen JQ and Liu JL: COX-2 inhibitors and gastric cancer. Gastroenterol Res Pract. 2014:1323202014. View Article : Google Scholar : PubMed/NCBI
35	Schildberg C, Abbas M, Merkel S, Agaimy A, Dimmler A, Schlabrakowski A, Croner R, Leupolt J, Hohenberger W and Allgayer H: COX-2, TFF1, and Src define better prognosis in young patients with gastric cancer. J Surg Oncol. 108:409–413. 2013. View Article : Google Scholar : PubMed/NCBI
36	Chen Z, Liu M, Liu X, Huang S, Li L, Song B, Li H, Ren Q, Hu Z, Zhou Y and Qiao L: COX-2 regulates E-cadherin expression through the NF-kappaB/Snail signaling pathway in gastric cancer. Int J Mol Med. 32:93–100. 2013. View Article : Google Scholar : PubMed/NCBI
37	Tseng YC, Tsai YH, Tseng MJ, Hsu KW, Yang MC, Huang KH, Li AF, Chi CW, Hsieh RH, Ku HH and Yeh TS: Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol Carcinog. 51:939–951. 2012. View Article : Google Scholar : PubMed/NCBI
38	Targosz A, Brzozowski T, Pierzchalski P, Szczyrk U, Ptak-Belowska A, Konturek SJ and Pawlik W: Helicobacter pylori promotes apoptosis, activates cyclooxygenase (COX)-2 and inhibits heat shock protein HSP70 in gastric cancer epithelial cells. Inflam Res. 61:955–966. 2012. View Article : Google Scholar
39	Shin WG, Kim HJ, Cho SJ, Kim HS, Kim KH, Jang MK, Lee JH and Kim HY: The COX-2-1195AA genotype is associated with diffuse-type gastric cancer in Korea. Gut Liver. 6:321–327. 2012. View Article : Google Scholar : PubMed/NCBI
40	Sun WH, Yu Q, Shen H, Ou XL, Cao DZ, Yu T, Qian C, Zhu F, Sun YL, Fu XL and Su H: Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis. World J Gastroenterol. 10:2809–2813. 2004. View Article : Google Scholar : PubMed/NCBI
41	Zucker S, Lysik RM, DiMassimo BI, Zarrabi HM, Moll UM, Grimson R, Tickle SP and Docherty AJ: Plasma assay of gelatinase B: tissue inhibitor of metalloproteinase complexes in cancer. Cancer. 76:700–708. 1995. View Article : Google Scholar : PubMed/NCBI
42	Groblewska M, Siewko M, Mroczko B and Szmitkowski M: The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer. Folia Histochem Cytobiol. 50:12–19. 2012. View Article : Google Scholar : PubMed/NCBI
43	Li M, Yang G, Xie B, Babu K and Huang C: Changes in matrix metalloproteinase-9 levels during progression of atrial fibrillation. J Int Med Res. 42:224–230. 2014. View Article : Google Scholar : PubMed/NCBI
44	Avci N, Ture M, Deligonul A, Cubukcu E, Olmez OF, Sahinturk S, Topak A, Kurt E, Evrensel T, Şahin AB and Yakut T: Association and prognostic significance of the functional −1562C/T polymorphism in the promoter region of MMP-9 in Turkish patients with gastric cancer. Pathol Oncol Res. 21:1243–1247. 2015. View Article : Google Scholar : PubMed/NCBI
45	Xia Y, Lian S, Khoi PN, Yoon HJ, Joo YE, Chay KO, Kim KK and Do Jung Y: Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells. PloS One. 10:e01240072015. View Article : Google Scholar : PubMed/NCBI
46	Akter H, Park M, Kwon OS, Song EJ, Park WS and Kang MJ: Activation of matrix metalloproteinase-9 (MMP-9) by neurotensin promotes cell invasion and migration through ERK pathway in gastric cancer. Tumour Biol. 36:6053–6062. 2015. View Article : Google Scholar : PubMed/NCBI
47	Shan YQ, Ying RC, Zhou CH, Zhu AK, Ye J, Zhu W, Ju TF and Jin HC: MMP-9 is increased in the pathogenesis of gastric cancer by the mediation of HER2. Cancer Gene Ther. 22:101–107. 2015. View Article : Google Scholar : PubMed/NCBI
48	Shimura T, Dagher A, Sachdev M, Ebi M, Yamada T, Yamada T, Joh T and Moses MA: Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer. Cancer Prev Res (Phila). 8:240–248. 2015. View Article : Google Scholar : PubMed/NCBI
49	Yamatoji M, Kasamatsu A, Kouzu Y, Koike H, Sakamoto Y, Ogawara K, Shiiba M, Tanzawa H and Uzawa K: Dermatopontin: A potential predictor for metastasis of human oral cancer. Int J Cancer. 130:2903–2911. 2012. View Article : Google Scholar : PubMed/NCBI
50	Docea AO, Mitruţ P, Grigore D, Pirici D, Călina DC and Gofiţă E: Immunohistochemical expression of TGF beta (TGF-beta), TGF beta receptor 1 (TGFBR1), and Ki67 in intestinal variant of gastric adenocarcinomas. Rom J Morphol Embryol. 53 Suppl 3:S683–S692. 2012.
51	Shinto O, Yashiro M, Kawajiri H, Shimizu K, Shimizu T, Miwa A and Hirakawa K: Combination effect of a TGF-beta receptor kinase inhibitor with 5-FU analog S1 on lymph node metastasis of scirrhous gastric cancer in mice. Cancer Sci. 101:1846–1852. 2010. View Article : Google Scholar : PubMed/NCBI
52	Park D II, Son HJ, Song SY, Choe WH, Lim YJ, Park SJ, Kim JJ, Kim YH, Rhee PL, Paik SW, et al: Role of TGF-beta 1 and TGF-beta type II receptor in gastric cancer. The Korean J Intern Med. 17:160–166. 2002. View Article : Google Scholar : PubMed/NCBI
53	Park SH, Kim YS, Park BK, Hougaard S and Kim SJ: Sequence-specific enhancer binding protein is responsible for the differential expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines: Implication for the loss of TGF-beta type II receptor expression. Oncogene. 20:1235–1245. 2001. View Article : Google Scholar : PubMed/NCBI