General Research Article

TRPM8 as a Potential Biomarker and Therapeutic Target for Gastric Cancer Identified by a Combination of Text Mining and RNA Sequencing

Author(s): Na Kong, Wendong Li, Jun Zhang, Xin Wang, Lin Hu and Qiqi Xu*

Volume 23, Issue 5, 2023

Published on: 13 June, 2023

Page: [391 - 399] Pages: 9

DOI: 10.2174/1566523223666230529142423

Price: $65

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Abstract

Introduction: Gastric cancer is a well-known malignant tumor that causes millions of deaths worldwide every year. Due to the lack of a specific biomarker for gastric cancer, most patients are diagnosed at an advanced stage of the disease which results in a poor prognosis and a higher death rate. Therefore, novel biomarkers are urgently needed for early diagnosis and to improve the survival rate.

Methods: In this study, we conducted RNA sequencing of tumor samples from 21 patients with gastric cancer. A total of 3192 differentially expressed genes (1589 up-regulated and 1603 down-regulated) were identified. Subsequently, we applied a text-mining algorithm for further analysis of these data and selected 30 representative genes to investigate as candidates for novel biomarkers in gastric cancer.

Results: Among these genes, we confirmed transient receptor potential melastatin 8 channels (TRPM8) as a novel biomarker based on Western blot and immunochemistry validation performed on 134 samples. Compared to normal gastric tissue, the tumor tissues exhibited a significantly higher expression level of TRPM8.

Conclusion: This study provides insights into the underlying role of TRPM8 in cell proliferation. In addition, TRPM8 may be used as a potential therapeutic target for patients with gastric cancer.

Keywords: TRPM8, gastric cancer, proliferation, text mining, biomarker, oncogenes.

Graphical Abstract
[1]
Digklia A, Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol 2016; 22(8): 2403-14.
[http://dx.doi.org/10.3748/wjg.v22.i8.2403] [PMID: 26937129]
[2]
Smyth EC, Nilsson M, Grabsch HI, van Grieken NCT, Lordick F. Gastric cancer. Lancet 2020; 396(10251): 635-48.
[http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]
[3]
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359-86.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[4]
Feng RM, Zong YN, Cao SM, Xu RH. Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics? Cancer Commun 2019; 39(1): 22.
[http://dx.doi.org/10.1186/s40880-019-0368-6] [PMID: 31030667]
[5]
Degiuli M, De Manzoni G, Di Leo A, et al. Gastric cancer: Current status of lymph node dissection. World J Gastroenterol 2016; 22(10): 2875-93.
[http://dx.doi.org/10.3748/wjg.v22.i10.2875] [PMID: 26973384]
[6]
Guo J, Dong B, Ji JF, Wu AW. Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients. World J Gastroenterol 2012; 18(38): 5434-41.
[http://dx.doi.org/10.3748/wjg.v18.i38.5434] [PMID: 23082061]
[7]
He C, Bian XY, Ni XZ, et al. Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer. World J Gastroenterol 2013; 19(14): 2171-8.
[http://dx.doi.org/10.3748/wjg.v19.i14.2171] [PMID: 23599643]
[8]
Jovanović J, Bagheri E. Semantic annotation in biomedicine: The current landscape. J Biomed Semantics 2017; 8(1): 44.
[http://dx.doi.org/10.1186/s13326-017-0153-x] [PMID: 28938912]
[9]
Altman RB, Bergman CM, Blake J, et al. Text mining for biology--the way forward: Opinions from leading scientists. Genome Biol 2008; 9 (Suppl. 2): S7.
[10]
Xiao Z, Hu L, Yang L, et al. TGFβ2 is a prognostic-related biomarker and correlated with immune infiltrates in gastric cancer. J Cell Mol Med 2020; 24(13): 7151-62.
[http://dx.doi.org/10.1111/jcmm.15164] [PMID: 32530106]
[11]
Xu Q, Kong N, Zhang J, Bai N, Bi J, Li W. Expression of transient receptor potential cation channel subfamily M member 8 in gastric cancer and its clinical significance. Exp Ther Med 2021; 21(4): 377.
[http://dx.doi.org/10.3892/etm.2021.9808] [PMID: 33680099]
[12]
Jensen LJ, Saric J, Bork P. Literature mining for the biologist: From information retrieval to biological discovery. Nat Rev Genet 2006; 7(2): 119-29.
[http://dx.doi.org/10.1038/nrg1768] [PMID: 16418747]
[13]
Wu J, Feng X, Guan R, Liang Y. Cancer research trend analysis based on fusion feature representation. Entropy 2021; 23(3): 338.
[http://dx.doi.org/10.3390/e23030338] [PMID: 33809188]
[14]
Hassani H, Beneki C, Unger S, Mazinani MT, Yeganegi MR. Text mining in big data analytics. Big Data Cogn 2020; 4(1): 1.
[http://dx.doi.org/10.3390/bdcc4010001]
[15]
Gonzalez GH, Tahsin T, Goodale BC, Greene AC, Greene CS. Recent advances and emerging applications in text and data mining for biomedical discovery. Brief Bioinform 2016; 17(1): 33-42.
[http://dx.doi.org/10.1093/bib/bbv087] [PMID: 26420781]
[16]
Tsavaler L, Shapero MH, Morkowski S, Laus R. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 2001; 61(9): 3760-9.
[PMID: 11325849]
[17]
Liu Y, Mikrani R, He Y, et al. TRPM8 channels: A review of distribution and clinical role. Eur J Pharmacol 2020; 882173312
[http://dx.doi.org/10.1016/j.ejphar.2020.173312] [PMID: 32610057]
[18]
Hantute-Ghesquier A, Haustrate A, Prevarskaya N, Lehen’kyi V. TRPM family channels in cancer. Pharmaceuticals 2018; 11(2): 58.
[http://dx.doi.org/10.3390/ph11020058] [PMID: 29875336]
[19]
Zhang L, Barritt GJ. Evidence that TRPM8 is an androgen-dependent Ca2+ channel required for the survival of prostate cancer cells. Cancer Res 2004; 64(22): 8365-73.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2146] [PMID: 15548706]
[20]
Legrand G, Humez S, Slomianny C, et al. Ca2+ pools and cell growth. Evidence for sarcoendoplasmic Ca2+-ATPases 2B involvement in human prostate cancer cell growth control. J Biol Chem 2001; 276(50): 47608-14.
[http://dx.doi.org/10.1074/jbc.M107011200] [PMID: 11606580]
[21]
Yang ZH, Wang XH, Wang HP, Hu LQ. Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells. Asian J Androl 2009; 11(2): 157-65.
[http://dx.doi.org/10.1038/aja.2009.1] [PMID: 19234481]
[22]
Gkika D, Flourakis M, Lemonnier L, Prevarskaya N. PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression. Oncogene 2010; 29(32): 4611-6.
[http://dx.doi.org/10.1038/onc.2010.210] [PMID: 20531306]
[23]
Cucu D, Chiritoiu G, Petrescu S, et al. Characterization of functional transient receptor potential melastatin 8 channels in human pancreatic ductal adenocarcinoma cells. Pancreas 2014; 43(5): 795-800.
[http://dx.doi.org/10.1097/MPA.0000000000000106] [PMID: 24658318]
[24]
Borrelli F, Pagano E, Romano B, et al. Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid. Carcinogenesis 2014; 35(12): 2787-97.
[http://dx.doi.org/10.1093/carcin/bgu205] [PMID: 25269802]
[25]
Yee NS, Zhou W, Lee M. Transient receptor potential channel TRPM8 is over-expressed and required for cellular proliferation in pancreatic adenocarcinoma. Cancer Lett 2010; 297(1): 49-55.
[http://dx.doi.org/10.1016/j.canlet.2010.04.023] [PMID: 20605675]
[26]
Li Q, Wang X, Yang Z, Wang B, Li S. Menthol induces cell death via the TRPM8 channel in the human bladder cancer cell line T24. Oncology 2009; 77(6): 335-41.
[http://dx.doi.org/10.1159/000264627] [PMID: 19955836]
[27]
Fan H, Shen YX, Yuan YF. Expression and prognostic roles of TRPV5 and TRPV6 in non-small cell lung cancer after curative resection. Asian Pac J Cancer Prev 2014; 15(6): 2559-63.
[http://dx.doi.org/10.7314/APJCP.2014.15.6.2559] [PMID: 24761864]
[28]
Wong KK, Banham AH, Yaacob NS, Nur Husna SM. The oncogenic roles of TRPM ion channels in cancer. J Cell Physiol 2019; 234(9): 14556-73.
[http://dx.doi.org/10.1002/jcp.28168] [PMID: 30710353]
[29]
Lashinger ESR, Steiginga MS, Hieble JP, et al. AMTB, a TRPM8 channel blocker: Evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol 2008; 295(3): F803-10.
[http://dx.doi.org/10.1152/ajprenal.90269.2008] [PMID: 18562636]
[30]
Liu Z, Wu H, Wei Z, et al. TRPM8: A potential target for cancer treatment. J Cancer Res Clin Oncol 2016; 142(9): 1871-81.
[http://dx.doi.org/10.1007/s00432-015-2112-1] [PMID: 26803314]
[31]
Zhao W, Xu H. High expression of TRPM8 predicts poor prognosis in patients with osteosarcoma. Oncol Lett 2016; 12(2): 1373-9.
[http://dx.doi.org/10.3892/ol.2016.4764] [PMID: 27446440]
[32]
Valero ML, Mello de Queiroz F, Stühmer W, Viana F, Pardo LA. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells. PLoS One 2012; 7(12)e51825
[http://dx.doi.org/10.1371/journal.pone.0051825] [PMID: 23251635]
[33]
Yu S, Xu Z, Zou C, et al. Ion channel TRPM8 promotes hypoxic growth of prostate cancer cells via an O2 -independent and RACK1-mediated mechanism of HIF-1α stabilization. J Pathol 2014; 234(4): 514-25.
[http://dx.doi.org/10.1002/path.4413] [PMID: 25065497]

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