Long noncoding RNAs (lncRNAs) have been shown to be involved in the development and progression of advanced gastric cancer (AGC). However, the roles of lncRNAs in advanced gastric cancer during the process of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are not well understood. A high-throughput microarray analysis was performed to compare the expression profiles of lncRNAs and messenger RNAs (mRNAs) in AGC serum samples during the process of CRS + HIPEC. Several potentially AGC-associated lncRNAs were verified by real-time quantitative reverse transcription polymerase chain reaction (PCR) analysis. Using abundant and varied probes, we were able to assess 33,045 lncRNAs and 30,215 mRNAs in our microarray. We found that 566 lncRNAs were differentially expressed (2-fold change) in AGC serum samples, indicating the significantly up- or downregulated lncRNAs play important roles in AGC during the process of CRS + HIPEC. Quantitative PCR results further verified that eight lncRNAs were aberrantly expressed in AGC serum samples after CRS + HIEC compared with matched serum sample before CRS + HIPEC. Among them, BC031243 and RP11-356I2.2 were the most aberrantly expressed lncRNAs, as estimated by quantitative PCR in six pairs of AGC serum samples. Our study demonstrated the expression patterns of lncRNAs in AGC serums before and after CRS + HIPEC by microarray. These results revealed that lncRNAs were differentially expressed during the process of CRS + HIPEC, suggesting that they might play key roles in tumor development.
Advanced gastric cancer (AGC) Cytoreductive surgery (CRS) Hyperthermic intraperitoneal chemotherapy (HIPEC) LncRNAs
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This work was supported by Guangdong Province Natural Science Fund (No. S2013010016662), the health bureau of Guangdong province (Nos. A2014224 and B2014196), Science and Technology Planning Project of Guangdong Province (No. 2013B021800284), and the National Natural Science Foundation of China (Nos. 81201932 and 81372493).
Conflicts of interest
The authors declare no competing financial interests.
XQ. Z and HJ. S designed the research; XL. Z, JP. W, and HS. T, XQ. Z, HJ.S contributed equally to this work; other authors reviewed and revised the manuscript.
Liu L, Wang S, Cao X, Liu J. Diagnostic value of circulating microRNAs for gastric cancer in asian populations: a meta-analysis. Tumour Biol. 2014;35(12):11995–2004.CrossRefPubMedGoogle Scholar
Pinheiro DD, Ferreira WA, Barros MB, Araujo MD, Rodrigues-Antunes S, Borges BD. Perspectives on new biomarkers in gastric cancer: diagnostic and prognostic applications. World J Gastroenterol. 2014;20:11574–85.CrossRefPubMedCentralGoogle Scholar
Montori G, Coccolini F, Ceresoli M, Catena F, Colaianni N, Poletti E. The treatment of peritoneal carcinomatosis in advanced gastric cancer: state of the art. Int J Surg Oncol. 2014;2014, 912418.PubMedPubMedCentralGoogle Scholar
Zhang XL, Shi HJ, Wang JP, Tang HS, Wu YB, Fang ZY, et al. MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin. World J Gastroenterol. 2014;20:11347–55.CrossRefPubMedPubMedCentralGoogle Scholar
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA hotair reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentralGoogle Scholar
Lu J, Xie F, Geng L, Shen W, Sui C, Yang J. Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV. Tumour Biol. 2014. doi:10.1007/s13277-014-2951-4.
He X, Tan X, Wang X, Jin H, Liu L, Ma L, et al. C-myc-activated long noncoding RNA ccat1 promotes colon cancer cell proliferation and invasion. Tumour Biol. 2014;35(12):12181–8.CrossRefPubMedGoogle Scholar
Li J, Liu D, Hua R, Zhang J, Liu W, Huo Y, et al. Long non-coding RNAs expressed in pancreatic ductal adenocarcinoma and lncRNA bc008363 an independent prognostic factor in pdac. Pancreatology. 2014;14(5):385–90.CrossRefPubMedGoogle Scholar
Guo Q, Zhao Y, Chen J, Hu J, Wang S, Zhang D, et al. Braf-activated long non-coding RNA contributes to colorectal cancer migration by inducing epithelial-mesenchymal transition. Oncol Lett. 2014;8:869–75.PubMedPubMedCentralGoogle Scholar
Wang Y, Zhang D, Wu K, Zhao Q, Nie Y, Fan D. Long noncoding RNA mrul promotes abcb1 expression in multidrug-resistant gastric cancer cell sublines. Mol Cell Biol. 2014;34:3182–93.CrossRefPubMedPubMedCentralGoogle Scholar
Hou P, Zhao Y, Li Z, Yao R, Ma M, Gao Y, et al. LincRNA-ror induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell Death Dis. 2014;5:e1287.CrossRefPubMedPubMedCentralGoogle Scholar
Nie FQ, Zhu Q, Xu TP, Zou YF, Xie M, Sun M, et al. Long non-coding RNA MVIH indicates a poor prognosis for non-small cell lung cancer and promotes cell proliferation and invasion. Tumour Biol. 2014;35:7587–94.CrossRefPubMedGoogle Scholar
Yang F, Xue X, Bi J, Zheng L, Zhi K, Gu Y, et al. Long noncoding RNA ccat1, which could be activated by c-myc, promotes the progression of gastric carcinoma. J Cancer Res Clin Oncol. 2013;139:437–45.CrossRefPubMedGoogle Scholar
Vigetti D, Deleonibus S, Moretto P, Bowen T, Fischer JW, Grandoch M, et al. Natural antisense transcript for hyaluronan synthase 2 (has2-as1) induces transcription of has2 via protein o-glcnacylation. J Biol Chem. 2014;289(42):28816–26.CrossRefPubMedPubMedCentralGoogle Scholar
Tong YS, Zhou XL, Wang XW, Wu QQ, Yang TX, Lv J, et al. Association of decreased expression of long non-coding RNA loc285194 with chemoradiotherapy resistance and poor prognosis in esophageal squamous cell carcinoma. J Transl Med. 2014;12:233.CrossRefPubMedPubMedCentralGoogle Scholar
Wu Y, Zhang L, Wang Y, Li H, Ren X, Wei F, et al. Long noncoding RNA hotair involvement in cancer. Tumour Biol. 2014;35(10):9531–8.CrossRefPubMedGoogle Scholar
Kitayama J. Intraperitoneal chemotherapy against peritoneal carcinomatosis: current status and future perspective. Surg Oncol. 2014;23:99–106.CrossRefPubMedGoogle Scholar
Thomassen I, van Gestel YR, van Ramshorst B, Luyer MD, Bosscha K, Nienhuijs SW, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014;134:622–8.CrossRefPubMedGoogle Scholar
Konigsrainer I, Horvath P, Struller F, Konigsrainer A, Beckert S. Initial clinical experience with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in signet-ring cell gastric cancer with peritoneal metastases. J Gastric Cancer. 2014;14:117–22.CrossRefPubMedPubMedCentralGoogle Scholar
Dedrick RL, Flessner MF. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst. 1997;89:480–7.CrossRefPubMedGoogle Scholar
Okines A, Verheij M, Allum W, Cunningham D, Cervantes A. Gastric cancer: esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v50–4.CrossRefPubMedGoogle Scholar
Roviello F, Caruso S, Marrelli D, Pedrazzani C, Neri A, De Stefano A, et al. Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: state of the art and future developments. Surg Oncol. 2011;20:e38–54.CrossRefPubMedGoogle Scholar
Konstantinidis IT, Young C, Tsikitis VL, Lee E, Jie T, Ong ES. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion: the University of Arizona early experience. World J Gastrointest Surg. 2012;4:135–40.CrossRefPubMedPubMedCentralGoogle Scholar
Ghosal S, Das S, Chakrabarti J. Long noncoding RNAs: new players in the molecular mechanism for maintenance and differentiation of pluripotent stem cells. Stem Cells Dev. 2013;22:2240–53.CrossRefPubMedPubMedCentralGoogle Scholar
Chakravadhanula M, Ozols VV, Hampton CN, Zhou L, Catchpoole D, Bhardwaj RD. Expression of the hox genes and hotair in atypical teratoid rhabdoid tumors and other pediatric brain tumors. Cancer Genet. 2014;207(9):425–8.CrossRefPubMedGoogle Scholar
Vincent-Salomon A, Ganem-Elbaz C, Manie E, Raynal V, Sastre-Garau X, Stoppa-Lyonnet D, et al. X inactive-specific transcript RNA coating and genetic instability of the X chromosome in brca1 breast tumors. Cancer Res. 2007;67:5134–40.CrossRefPubMedGoogle Scholar
Takahashi H, Carninci P. Widespread genome transcription: new possibilities for RNA therapies. Biochem Biophys Res Commun. 2014;452(2):294–301.CrossRefPubMedGoogle Scholar
Shi R, Zhou JY, Zhou H, Zhao Z, Liang SH, Zheng WL, et al. The role of pinx1 in growth control of breast cancer cells and its potential molecular mechanism by mRNA and lncRNA expression profiles screening. Biomed Res Int. 2014;2014:978984.PubMedPubMedCentralGoogle Scholar
Lai F, Orom UA, Cesaroni M, Beringer M, Taatjes DJ, Blobel GA, et al. Activating RNAs associate with mediator to enhance chromatin architecture and transcription. Nature. 2013;494:497–501.CrossRefPubMedPubMedCentralGoogle Scholar