TNNT2 as a potential biomarker for the progression and prognosis of colorectal cancer

Jing,Li; Feng,Li; Zhou,Zhiguo; Shi,Shuai; Deng,Ruoying; Wang,Zhicong; Zhang,Yi; Ren,Zhixue; Liu,Yibing

doi:10.3892/or.2020.7637

TNNT2 as a potential biomarker for the progression and prognosis of colorectal cancer

Authors:
- Li Jing
- Li Feng
- Zhiguo Zhou
- Shuai Shi
- Ruoying Deng
- Zhicong Wang
- Yi Zhang
- Zhixue Ren
- Yibing Liu
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Affiliations: Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Radiotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, The Seven People's Hospital of Hebei Province, Dingzhou, Hebei 073000, P.R. China
Published online on: June 9, 2020 https://doi.org/10.3892/or.2020.7637
Pages: 628-636
Copyright: © Jing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. At present, there are limited effective biomarkers of CRC. The present study aimed to identify potential signatures associated with the tumorigenesis and prognosis of CRC using publicly available databases, and further validate the identified biomarkers in CRC cell lines. Identification of differentially expressed mRNAs between CRC and paracancerous samples was conducted based on data from The Cancer Genome Atlas (TCGA; 471 tumor samples and 41 normal samples). Survival analysis was performed to explore the prognostic value of troponin 2 (TNNT2) in the TCGA training set, which was further validated in an external dataset, GSE17531. Functional enrichment analysis was conducted to determine the possible biological functions using GSEA 3.0. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting were utilized to detect the mRNA and protein expression levels of TNNT2 between CRC and normal colorectal cells. Immunohistochemistry was performed to detect the protein expression of TNNT2 in CRC and normal tissues. TNNT2 was significantly upregulated in CRC samples compared with adjacent normal samples in the TCGA dataset. Increased expression of TNNT2 was associated with inferior prognosis in the TCGA training dataset and GSE17531 validation dataset. Functional enrichment analysis revealed that the ErbB signaling pathway and glycerophospholipid metabolism pathway were significantly activated in the TNNT2 high expression group. Overexpression of TNNT2 mRNA and TNNT2 protein in CRC tumor cells was confirmed by RT‑qPCR and western blotting, respectively. Immunohistochemistry indicated increased protein expression levels of TNNT2 in CRC tissues in comparison with normal tissues. TNNT2 was associated with the tumorigenesis and prognosis of CRC, which may be useful for novel biomarker identification and targeted therapeutic strategy development.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Douaiher J, Ravipati A, Grams B, Chowdhury S, Alatise O and Are C: Colorectal cancer-global burden, trends, and geographical variations. J Surg Oncol. 115:619–630. 2017. View Article : Google Scholar : PubMed/NCBI
3	Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi RE and Corcione F: Worldwide burden of colorectal cancer: A review. Updates Surg. 68:7–11. 2016. View Article : Google Scholar : PubMed/NCBI
4	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
5	Zheng R, Zeng H, Zhang S, Chen T and Chen W: National estimates of cancer prevalence in China, 2011. Cancer Lett. 370:33–38. 2016. View Article : Google Scholar : PubMed/NCBI
6	Karanikas M and Esebidis A: Increasing incidence of colon cancer in patients <50 years old: A new entity? Ann Transl Med. 4:1642016. View Article : Google Scholar : PubMed/NCBI
7	Zhang X, Shao S, Gao Y, Zhang M and Lu Y: Meta-analysis of relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi. 19:334–338. 2016.(In Chinese). PubMed/NCBI
8	Brenner H, Kloor M and Pox CP: Colorectal cancer. Lancet. 383:1490–1502. 2014. View Article : Google Scholar : PubMed/NCBI
9	Yusup A, Wang HJ, Rahmutula A, Sayim P, Zhao ZL and Zhang GQ: Clinical features and prognosis in colorectal cancer patients with different ethnicities in Northwest China. World J Gastroenterol. 41:7183–7188. 2013. View Article : Google Scholar
10	Ren Q and Jin B: The clinical value and biological function of PTTG1 in colorectal cancer. Biomed Pharmacother. 89:108–115. 2017. View Article : Google Scholar : PubMed/NCBI
11	Gil J, Ramsey D, Szmida E, Leszczynski P, Pawlowski P, Bebenek M and Sasiadek MM: TheBAXgene as a candidate for negative autophagy-related genes regulator on mRNA levels in colorectal cancer. Med Oncol. 34:162017. View Article : Google Scholar : PubMed/NCBI
12	Mansour MA and Senga T: HOXD8 exerts a tumor-suppressing role in colorectal cancer as an apoptotic inducer. Int J Biochem Cell Biol. 88:1–13. 2017. View Article : Google Scholar : PubMed/NCBI
13	Roelofs HM, Te Morsche RH, van Heumen BW, Nagengast FM and Peters WH: Over-expression of COX-2 mRNA in colorectal cancer. BMC Gastroenterology. 14:12014. View Article : Google Scholar : PubMed/NCBI
14	Zhang JS, Yang LQ, Du BR and Gao H: Higher RABEX-5 mRNA predicts unfavourable survival in patients with colorectal cancer. Eur Rev Med Pharmacol Sci. 21:2372–2376. 2017.PubMed/NCBI
15	Wang L, Shen X, Wang Z, Xiao X, Wei P, Wang Q, Ren F, Wang Y, Liu Z, Sheng W, et al: A molecular signature for the prediction of recurrence in colorectal cancer. Mol Cancer. 14:222015. View Article : Google Scholar : PubMed/NCBI
16	Yarden Y and Pines G: The ERBB network: At last, cancer therapy meets systems biology. Nat Rev Cancer. 12:553–563. 2012. View Article : Google Scholar : PubMed/NCBI
17	Hynes NE and Lane HA: ERBB receptors and cance: The complexity of targeted inhibitors. Nat Rev Cancer. 5:341–354. 2005. View Article : Google Scholar : PubMed/NCBI
18	Wang H, Xi Q and Wu G: Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway. Cancer Med. 5:1599–1606. 2016. View Article : Google Scholar : PubMed/NCBI
19	Li N, Bu X, Tian X, Wu P, Yang L and Huang P: Fatty acid synthase regulates proliferation and migration of colorectal cancer cells Via HER2-PI3K/Akt signaling pathway. Nutr Cancer. 64:864–870. 2012. View Article : Google Scholar : PubMed/NCBI
20	Nikolayeva O and Robinson MD: edgeR for Differential RNA-seq and ChIP-seq Analysis: An application to stem cell biology. Methods Mol Biol. 1150:45–79. 2014. View Article : Google Scholar : PubMed/NCBI
21	Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI
22	Gazzoni GF, Fraga MB, Ferrari ADL, Soliz PDC, Borges AP, Bartholomay E, Kalil CAA, Giaretta V and Rohde LEP: Predictors of total mortality and echocardiographic response for cardiac resynchronization therapy: A cohort study. Arq Bras Cardiol. 109:569–578. 2017.(In English, Portuguese). PubMed/NCBI
23	Kang JS, Lee S, Son D, Han Y, Lee KB, Kim JR, Kwon W, Kim SW and Jang JY: Prognostic predictability of the new American Joint Committee on Cancer 8th staging system for distal bile duct cancer: Limited usefulness compared with the 7th staging system. J Hepatobiliary Pancreat Sci. 25:124–130. 2018. View Article : Google Scholar : PubMed/NCBI
24	Liu L, Shi M, Wang Z, Lu H, Li C, Tao Y, Chen X and Zhao J: A molecular and staging model predicts survival in patients with resected non-small cell lung cancer. BMC Cancer. 18:9662018. View Article : Google Scholar : PubMed/NCBI
25	Ohtsuki I and Morimoto S: Troponin: Regulatory function and disorders. Biochem Biophys Res Commun. 369:62–73. 2008. View Article : Google Scholar : PubMed/NCBI
26	Wei B and Jin JP: TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure-function relationships. Gene. 582:1–13. 2016. View Article : Google Scholar : PubMed/NCBI
27	Van Spaendonck-Zwarts KY, Van Rijsingen IA, Van den Berg MP, Lekanne Deprez RH, Post JG, van Mil AM, Asselbergs FW, Christiaans I, van Langen IM, Wilde AA, et al: Genetic analysis in 418 index patients with idiopathic dilated cardiomyopathy: Overview of 10 years' experience. Eur J Heart Fail. 15:628–636. 2013. View Article : Google Scholar : PubMed/NCBI
28	Kong SW, Hu YW, Ho JW, Ikeda S, Polster S, John R, Hall JL, Bisping E, Pieske B, dos Remedios CG and Pu WT: Heart failure-associated changes in RNA splicing of sarcomere genes. Circ Cardiovasc Genet. 3:138–146. 2010. View Article : Google Scholar : PubMed/NCBI
29	Kozlovski I, Siegfried Z, Amar-Schwartz A and Karni R: The role of RNA alternative splicing in regulating cancer metabolism. Human Genet. 136:1113–1127. 2017. View Article : Google Scholar
30	Munkley J, Livermore K, Rajan P and Elliott DJ: RNA splicing and splicing regulator changes in prostate cancer pathology. Hum Genet. 136:1143–1154. 2017. View Article : Google Scholar : PubMed/NCBI
31	Lokody I: Alternative splicing: Aberrant splicing promotes colon tumour growth. Nat Rev Cancer. 14:382–383. 2014. View Article : Google Scholar : PubMed/NCBI
32	Zong Z, Li H, Yi C, Ying H, Zhu Z and Wang H: Genome-wide profiling of prognostic alternative splicing signature in colorectal cancer. Front Oncol. 8:5372018. View Article : Google Scholar : PubMed/NCBI
33	Adams JE III, Bodor GS, Dávila-Román VG, Delmez JA, Apple FS, Ladenson JH and Jaffe AS: Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 88:101–106. 1993. View Article : Google Scholar : PubMed/NCBI
34	De Luca A, Carotenuto A, Rachiglio A, Gallo M, Maiello MR, Aldinucci D, Pinto A and Normanno N: The role of the EGFR signaling in tumor microenvironment. J Cell Physiol. 214:559–567. 2008. View Article : Google Scholar : PubMed/NCBI
35	Mallini P, Lennard T, Kirby J and Meeson A: Epithelial-to-mesenchymal transition: What is the impact on breast cancer stem cells and drug resistance. Cancer Treat Rev. 40:341–348. 2014. View Article : Google Scholar : PubMed/NCBI
36	Spano JP, Fagard R, Soria JC, Rixe O, Khayat D and Milano G: Epidermal growth factor receptor signaling in colorectal cancer: Preclinical data and therapeutic perspectives. Ann Oncol. 16:189–194. 2005. View Article : Google Scholar : PubMed/NCBI
37	Hung CY, Yeh TS, Tsai CK, Wu RC, Lai YC, Chiang MH, Lu KY, Lin CN, Cheng ML and Lin G: Glycerophospholipids pathways and chromosomal instability in gastric cancer: Global lipidomics analysis. World J Gastrointest Oncol. 11:181–194. 2019. View Article : Google Scholar : PubMed/NCBI
38	Mika A, Kobiela J, Czumaj A, Chmielewski M, Stepnowski P and Sledzinski T: Hyper-elongation in colorectal cancer tissue-cerotic acid is a potential novel serum metabolic marker of colorectal malignancies. Cell Physiol Biochem. 41:722–730. 2017. View Article : Google Scholar : PubMed/NCBI
39	Mirnezami R, Spagou K, Vorkas PA, Lewis MR, Kinross J, Want E, Shion H, Goldin RD, Darzi A, Takats Z, et al: Chemical mapping of the colorectal cancer microenvironment via MALDI imaging mass spectrometry (MALDI-MSI) reveals novel cancer-associated field effects. Mol Oncol. 8:39–49. 2014. View Article : Google Scholar : PubMed/NCBI