Progress and prospects of biomarkers in primary liver cancer (Review)
- Authors:
- Yu‑Xue Gao
- Tong‑Wang Yang
- Ji‑Ming Yin
- Peng‑Xiang Yang
- Bu‑Xin Kou
- Meng‑Yin Chai
- Xiao‑Ni Liu
- De‑Xi Chen
-
Affiliations: Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China, Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China - Published online on: April 1, 2020 https://doi.org/10.3892/ijo.2020.5035
- Pages: 54-66
This article is mentioned in:
Abstract
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 | |
Gera S, Ettel M, Acosta-Gonzalez G and Xu R: Clinical features, histology, and histogenesis of combined hepatocellular-cholan-giocarcinoma. World J Hepatol. 6:300–309. 2017. View Article : Google Scholar | |
Saffroy R, Pham P, Reffas M, Takka M, Lemoine A and Debuire B: New perspectives and strategy research biomarkers for hepatocel-lular carcinoma. Clin Chem Lab Med. 45:1169–1179. 2007. View Article : Google Scholar | |
Zhou YM, Yang JM, Li B, Yin ZF, Xu F, Wang B, Liu P and Li ZM: Clinicopathologic characteristics of intrahepatic chol-angiocarcinoma in patients with positive serum a-fetoprotein. World J Gastroenterol. 14:2251–2254. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yin X, Zhang BH, Qiu SJ, Ren ZG, Zhou J, Chen XH, Zhou Y and Fan J: Combined hepatocellular carcinoma and cholangiocarci-noma: Clinical features, treatment modalities, and prognosis. Ann Surg Oncol. 19:2869–2876. 2012. View Article : Google Scholar : PubMed/NCBI | |
Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, Budhu A, Zanetti KA, Chen Y, Qin LX, et al: EpCAM and alpha‑fetoprotein expression defnes novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 68:1451–1461. 2008. View Article : Google Scholar : PubMed/NCBI | |
Li R, Yang D, Tang CL, Cai P, Ma KS, Ding SY, Zhang XH, Guo DY and Yan XC: Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: Clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography. BMC Cancer. 16:1582016. View Article : Google Scholar : PubMed/NCBI | |
Bertino G, Ardiri A, Malaguarnera M, Malaguarnera G, Bertino N and Calvagno GS: Hepatocellualar carcinoma serum markers. Semin Oncol. 39:410–433. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hagiwara S, Kudo M, Kawasaki T, Nagashima M, Minami Y, Chung H, Fukunaga T, Kitano M and Nakatani T: Prognostic factors for portal venous invasion in patients with hepatocellular carcinoma. J Gastroenterol. 41:1214–1219. 2006. View Article : Google Scholar | |
Tamura Y, Igarashi M, Kawai H, Suda T, Satomura S and Aoyagi Y: Clinical advantage of highly sensitive on-chip immunoassay for fucosylated fraction of alpha-fetoprotein in patients with hepatocellular carcinoma. Dig Dis Sci. 55:pp. 3576–3583. 2010, View Article : Google Scholar : PubMed/NCBI | |
Choi J, Kim GA, Han S, Lee W, Chun S and Lim YS: Longitudinal assessment of three serum biomarkers to detect very early stage hepatocellular carcinoma. Hepatology. 69:1983–1994. 2019. View Article : Google Scholar | |
Choi JY, Jung SW, Kim HY, Kim M, Kim Y, Kim DG and Oh EJ: Diagnostic value of AFP‑L3 and PIVKA‑II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 19:339–346. 2013. View Article : Google Scholar : PubMed/NCBI | |
Taketa K: Alpha-fetoprotein: Reevaluation in hepatology. Hepatology. 12:1420–1432. 1990. View Article : Google Scholar : PubMed/NCBI | |
Zhang YS, Chu JH, Cui SX, Song ZY and Qu XJ: Des‑γ-carboxy prothrombin (DCP) as a potential autologous growth factor for the development of hepatocellular carcinoma. Cell Physiol Biochem. 34:903–915. 2014. View Article : Google Scholar | |
Hu B, Tian X, Sun J and Meng X: Evaluation of individual and combined applications of serum biomarkers for diagnosis of hepatocellular carcinoma: A meta‑analysis. Int J Mol Sci. 14:23559–23580. 2013. View Article : Google Scholar : PubMed/NCBI | |
Volk ML, Hernandez JC, Su GL, Lok AS and Marrero JA: Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: A comparison of AFP, DCP, and AFP-L3. Cancer Biomark. 3:79–87. 2007. View Article : Google Scholar : PubMed/NCBI | |
Song P, Tobe RG, Inagaki Y, Kokudo N, Hasegawa K, Sugawara Y and Tang W: The management of hepatocellular carcinoma around the world: A comparison of guidelines from 2001 to 2011. Liver Int. 32:1053–1063. 2012. View Article : Google Scholar : PubMed/NCBI | |
Yamamoto K, Imamura H, Matsuyama Y, Kume Y, Ikeda H, Norman GL, Shums Z, Aoki T, Hasegawa K, Beck Y, et al: AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. J Gastroenterol. 45:1272–1282. 2010. View Article : Google Scholar : PubMed/NCBI | |
Chen J, Wu G and Li Y: Evaluation of serum des-gamma-carboxy prothrombin for the diagnosis of hepatitis B virus-related hepatocellular carcinoma: A meta-analysis. Dis Markers. 2018:pp. 89060232018, View Article : Google Scholar : PubMed/NCBI | |
Masuzaki R, Karp SJ and Omata M: New serum markers of hepatocellular carcinoma. Semin Oncol. 39:pp. 434–439. 2012, View Article : Google Scholar : PubMed/NCBI | |
Wang K, Guo W, Li N, Shi J, Zhang C, Lau WY, Wu M and Cheng S: Alpha‑1‑fucosidase as a prognostic indicator for hepatocellular carcinoma following hepatectomy: A large-scale, long-term study. Br J Cancer. 110:1811–1819. 2014. View Article : Google Scholar : PubMed/NCBI | |
Mintz K, Waidely E, Zhou Y, Peng Z, Al‑Youbi AO, Bashammakh AS, El‑Shahawi MS and Leblanc RM: Carbon dots and gold nanoparticles based immunoassay for detection of alpha-L-fucosidase. Anal Chim Acta. 1041:114–121. 2018. View Article : Google Scholar : PubMed/NCBI | |
El‑Tayeh SF, Hussein TD, El‑Houseini ME, Amer MA, El‑Sherbini M and Elshemey WM: Serological biomarkers of hepatocellular carcinoma in Egyptian patients. Dis Markers. 32:255–263. 2012. View Article : Google Scholar | |
Waidely E, Al‑Youbi AO, Bashammakh AS, El‑Shahawi MS and Leblanc RM: Alpha-l-fucosidase immunoassay for early detection of hepatocellular carcinoma. Anal Chem. 89:9459–9466. 2017. View Article : Google Scholar : PubMed/NCBI | |
Wei C, Yang X, Liu N, Geng J, Tai Y, Sun Z, Mei G, Zhou P, Peng Y, Wang C, et al: Tumor microenvironment regulation by the endoplasmic reticulum stress transmission mediator Golgi protein 73 in mice. Hepatology. 70:851–870. 2019. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Zhang X, Zhou S, Shi J, Xu Y, He J, Lin F, Wei A, Zhou L and Chen Z: Knockdown of Golgi phosphoprotein 73 blocks the trafficking of matrix metalloproteinase‑2 in hepatocellular carcinoma cells and inhibits cell invasion. J Cell Mol Med. 23:2399–2409. 2019. View Article : Google Scholar : PubMed/NCBI | |
Block TM, Comunale MA, Lowman M, Steel LF, Romano PR, Fimmel C, Tennant BC, London WT, Evans AA, Blumberg B S, et al: use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. Proc Natl Acad Sci USA. 102:pp. 779–784. 2005, View Article : Google Scholar : PubMed/NCBI | |
Mao Y, Yang H, Xu H, Lu X, Sang X, Du S, Zhao H, Chen W, Xu Y, Chi T, et al: Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 59:1687–1693. 2010. View Article : Google Scholar : PubMed/NCBI | |
Ibrahim GH, Mahmoud MA and Aly NM: Evaluation of circulating transforming growth factor-beta1, glypican-3 and Golgi protein-73 mRNAs expression as predictive markers for hepatocellular carcinoma in Egyptian patients. Mol Biol Rep. 40:7069–7075. 2013. View Article : Google Scholar : PubMed/NCBI | |
Zhang Z, Zhang Y, Wang Y, Xu L and Xu W: Alpha‑fetoprotein‑L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma. Onco Targets Ther. 9:123–129. 2015. | |
Lamort AS, Giopanou I, Psallidas I and Stathopoulos GT: Osteopontin as a link between infammation and cancer: The thorax in the spotlight. Cells. 8:pii: E815. 2019, View Article : Google Scholar | |
Ying X, Zhao Y, Wang JL, Zhou X, Zhao J, He CC, Guo XJ, Jin GH, Wang LJ, Zhu Q and Han SX: Serum anti‑osteopontin autoantibody as a novel diagnostic and prognostic biomarker in patients with hepatocellular carcinoma. Oncol Rep. 32:1550–1556. 2014. View Article : Google Scholar : PubMed/NCBI | |
Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, Sangrajrang S, Hainaut P, Marrero JA and Beretta L: Identification of osteo-pontin as a novel marker for early hepatocellular carcinoma. Hepatology. 55:483–490. 2012. View Article : Google Scholar | |
Zhu Y, Yang J, Xu D, Gao XM, Zhang Z, Hsu JL, Li CW, Lim SO, Sheng YY, Zhang Y, et al: Disruption of tumour-associated macrophage trafficking by the osteopontin‑induced colony‑stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade. Gut. 9:1653–1666. 2019. View Article : Google Scholar | |
Liu K, Duan J, Liu H, Yang X, Yang J, Wu M and Chang Y: Precancer antiviral treatment reduces microvascular invasion of early‑stage Hepatitis B‑related hepatocellular carcinoma. Sci Rep. 9:22202019. View Article : Google Scholar | |
Qin XL, Wang ZR, Shi JS, Lu M, Wang L and He QR: Utility of serum CA19-9 in diagnosis of cholangiocarcinoma: In comparison with CEA. World J Gastroenterol. 10:427–432. 2004. View Article : Google Scholar : PubMed/NCBI | |
Minato H, Nakanuma Y and Terada T: Expression of blood group-related antigens in cholangiocarcinoma in relation to non-neoplastic bile ducts. Histopathology. 28:411–419. 1996. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Li J, Xia Y, Gong R, Wang K, Yan Z, Wan X, Liu G, Wu D, Shi L, et al: Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol. 31:1188–1195. 2013. View Article : Google Scholar : PubMed/NCBI | |
Yamada T, Nakanishi Y, Okamura K, Tsuchikawa T, Nakamura T, Noji T, Asano T, Tanaka K, Kurashima Y, Ebihara Y, et al: Impact of serum carbohydrate antigen 19-9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol. Feb 10–2018, Epub ahead of print. View Article : Google Scholar | |
Carr BI, Kanke F, Wise M and Satomura S: Clinical evaluation of lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci. 52:776–782. 2007. View Article : Google Scholar : PubMed/NCBI | |
Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, Tateishi R, Han KH, Chawla YK, Shiina S, et al: Asia‑Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update. Hepatol Int. 11:317–370. 2017. View Article : Google Scholar : PubMed/NCBI | |
Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, Uemoto S, Kaneko S, Kawasaki S, Ku Y, et al: Evidence-based clinical practice guidelines for hepatocellular carcinoma: The Japan society of hepatology 2013 update (3rd JSH‑HCC Guidelines). Hepatol Res. 45:2015. View Article : Google Scholar | |
World Health Organization (WHO): Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. WHO; Geneva: 2015 | |
Zhou J, Sun HC, Wang Z, Cong WM, Wang JH, Zeng MS, Yang JM, Bie P, Liu LX, Wen TF, et al: Guidelines for diagnosis and treatment of primary liver cancer in China (2017 Edition). Liver Cancer. 7:235–260. 2018. View Article : Google Scholar : PubMed/NCBI | |
Nishida T and Kataoka H: Glypican 3-targeted therapy in hepatocellular carcinoma. Cancers (Basel). 11. pii: E1339. 2019, View Article : Google Scholar | |
Chen C, Huang X, Ying Z, Wu D, Yu Y, Wang X and Chen C: Can glypican‑3 be a disease‑specific biomarker? Clin Transl Med. 6:182017. View Article : Google Scholar | |
Shirakawa H, Kuronuma T, Nishimura Y, Hasebe T, Nakano M, Gotohda N, Takahashi S, Nakagohri T, Konishi M, Kobayashi N, et al: Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. Int J Oncol. 34:649–656. 2009.PubMed/NCBI | |
Capurro M, Wanless IR, Sherman M, Deboer G, Shi W, Miyoshi E and Filmus J: Glypican-3: A novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 125:89–97. 2003. View Article : Google Scholar : PubMed/NCBI | |
Kolluri A and Ho M: The role of glypican-3 in regulating Wnt, YAP, and hedgehog in liver cancer. Front Oncol. 9:7082019. View Article : Google Scholar : PubMed/NCBI | |
Liu H, Li P, Zhai Y, Qu CF, Zhang LJ, Tan YF, Li N and Ding HG: Diagnostic value of glypican-3 in serum and liver for primary hepa-tocellular carcinoma. World J Gastroenterol. 16:4410–4415. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wang L, Yao M, Pan LH, Qian Q and Yao DF: Glypican‑3 is a biomarker and a therapeutic target of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 14:361–366. 2015. View Article : Google Scholar : PubMed/NCBI | |
Han HH, Qiu YJ, Shi YY, Wen W, He XP, Dong LW, Tan YX, Long YT, Tian H and Wang HY: Glypican-3-targeted precision diagnosis of hepatocellular carcinoma on clinical sections with a supramolecular 2D imaging probe. Theranostics. 8:3268–3274. 2018. View Article : Google Scholar : PubMed/NCBI | |
Kakar S, Muir T, Murphy LM, Lloyd RV and Burgart LJ: Immunoreactivity of Hep Par 1 in hepatic and extrahepatic tumors and its correlation with albumin in situ hybridization in hepatocellular carcinoma. Am J Clin Patho. 119:361–366. 2003. View Article : Google Scholar | |
Leong AS, Sormunen RT, Tsui WM and Liew CT: Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology. 33:318–324. 1998. View Article : Google Scholar : PubMed/NCBI | |
Ibrahim TR and Abdel‑Raouf SM: Immunohistochemical study of glypican-3 and HepPar-1 in differentiating hepatocellular carcinoma from metastatic carcinomas in FNA of the liver. Pathol Oncol Res. 21:379–387. 2015. View Article : Google Scholar | |
Kakar S, Gown AM, Goodman ZD and Ferrell LD: Best practices in diagnostic immunohistochemistry: Hepatocellular carcinoma versus metastatic neoplasms. Arch Pathol Lab Med. 131:1648–1654. 2007.PubMed/NCBI | |
Wang C, Zhang Y, Guo K, Wang N, Jin H, Liu Y and Qin W: Heat shock proteins in hepatocellular carcinoma: Molecular mechanism and therapeutic potential. Int J Cancer. 138:1824–1834. 2016. View Article : Google Scholar : PubMed/NCBI | |
Chuma M, Sakamoto M, Yamazaki K, Ohta T, Ohki M, Asaka M and Hirohashi S: Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology. 37:198–207. 2003. View Article : Google Scholar | |
Shin E, Ryu HS, Kim SH, Jung H, Jang JJ and Lee K: The clinicopathological signifcance of heat shock protein 70 and glutamine synthetase expression in hepatocellular carcinoma. J Hepatobiliary Pancreat Sci. 18:pp. 544–550. 2011, View Article : Google Scholar : PubMed/NCBI | |
Kang GH, Lee BS, Lee ES, Kim SH, Lee HY and Kang DY: Prognostic significance of p53, mTOR, c-Met, IGF-1R, and HSP70 overexpression after the resection of hepatocellular carcinoma. Gut Liver. 8:79–87. 2014. View Article : Google Scholar : PubMed/NCBI | |
Evason KJ, Grenert J P, Ferrell LD and Kakar S: Atypical hepato-cellular adenoma-like neoplasms with β-catenin activation show cytogenetic alterations similar to well-differentiated hepatocellular carcinomas. Hum Pathol. 44:750–758. 2013. View Article : Google Scholar | |
Dal Bello B, Rosa L, Campanini N, Tinelli C, Torello Viera F, D'Ambrosio G, Rossi S and Silini EM: Glutamine synthetase immunostaining correlates with pathologic features of hepa-tocellular carcinoma and better survival after radiofrequency thermal ablation. Clin Cancer Res. 16:2157–2166. 2010. View Article : Google Scholar : PubMed/NCBI | |
Osada T, Nagashima I, Tsuno NH, Kitayama J and Nagawa H: Prognostic significance of glutamine synthetase expression in unifocal advanced hepatocellular carcinoma. J Hepatol. 33:247–253. 2000. View Article : Google Scholar : PubMed/NCBI | |
Nguyen TB, Roncalli M, Di Tommaso L and Kakar S: Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma. Mod Pathol. 29:283–292. 2016. View Article : Google Scholar : PubMed/NCBI | |
Uthamalingam P, Das A, Behra A, Kalra N and Chawla Y: Diagnostic value of glypican3, heat shock protein 70 and glutamine synthetase in hepatocellular carcinoma arising in cirrhotic and non-cirrhotic livers. J Clin Exp Hepatol. 8:173–180. 2018. View Article : Google Scholar : PubMed/NCBI | |
Lagana SM, Moreira RK, Remotti HE and Bao F: Glutamine synthetase, heat shock protein-70, and glypican-3 in intrahepatic cholangiocarcinoma and tumors metastatic to liver. Appl Immunohistochem Mol Morphol. 21:254–257. 2013. | |
Timek DT, Shi J, Liu H and Lin F: Arginase‑1, HepPar‑1, and Glypican-3 are the most effective panel of markers in distinguishing hepatocellular carcinoma from metastatic tumor on fine‑needle aspiration specimens. Am J Clin Pathol. 138:pp. 203–210. 2012, View Article : Google Scholar : PubMed/NCBI | |
Pesce JT, Ramalingam TR, Mentink‑Kane MM, Wilson MS, El Kasmi KC, Smith AM, Thompson RW, Cheever AW, Murray PJ and Wynn TA: Arginase-1-expressing macrophages suppress Th2 cytokine‑driven infammation and fibrosis. PLoS Pathog. 5:e10003712009. View Article : Google Scholar | |
Fujiwara M, Kwok S, Yano H and Pai RK: Arginase‑1 is a more sensitive marker of hepatic differentiation than HepPar-1 and glypican-3 in fine-needle aspiration biopsies. Cancer Cytopathol. 120:230–237. 2012. View Article : Google Scholar : PubMed/NCBI | |
Yan BC, Gong C, Song J, Krausz T, Tretiakova M, Hyjek E, Al‑Ahmadie H, Alves V, Xiao SY, Anders RA and Hart JA: Arginase-1: A new immunohistochemical marker of hepatocytes and hepatocellular neoplasms. Am J Surg Pathol. 34:pp. 1147–1154. 2010, View Article : Google Scholar : PubMed/NCBI | |
Moll R, Divo M and Langbein L: The human keratins: Biology and pathology. Histochem Cell Biol. 129:705–733. 2008. View Article : Google Scholar : PubMed/NCBI | |
Ryu HS, Lee K, Shin E, Kim SH, Jing J, Jung HY, Lee H and Jang JJ: Comparative analysis of immunohistochemical markers for differential diagnosis of hepatocelluar carcinoma and cholan-giocarcinoma. Tumori. 98:478–484. 2012. View Article : Google Scholar : PubMed/NCBI | |
Liu LZ, Yang LX, Zheng BH, Dong PP, Liu XY, Wang ZC, Zhou J, Fan J, Wang XY and Gao Q: CK7/CK19 index: A potential prognostic factor for postoperative intrahepatic cholangiocarcinoma patients. J Surg Oncol. 117:pp. 1531–1539. 2018, View Article : Google Scholar : PubMed/NCBI | |
Pinato DJ, Pirisi M, Maslen L and Sharma R: Tissue biomarkers of prognostic significance in hepatocellular carcinoma. Adv Anat Pathol. 21:270–284. 2014. View Article : Google Scholar : PubMed/NCBI | |
Calderaro J, Couchy G, Imbeaud S, Amaddeo G, Letouzé E, Blanc JF, Laurent C, Hajji Y, Azoulay D, Bioulac-Sage P, et al: Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol. 67:727–738. 2017. View Article : Google Scholar : PubMed/NCBI | |
Totoki Y, Tatsuno K, Covington KR, Ueda H, Creighton CJ, Kato M, Tsuji S, Donehower LA, Slagle BL, Nakamura H, et al: Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat Genet. 46:1267–1273. 2014. View Article : Google Scholar : PubMed/NCBI | |
Yu JI, Choi C, Ha SY, Park CK, Kang SY, Joh JW, Paik SW, Kim S, Kim M, Jung SH and Park HC: Clinical importance of TERT overexpression in hepatocellular carcinoma treated with curative surgical resection in HBV endemic area. Sci Rep. 7:122582017. View Article : Google Scholar : PubMed/NCBI | |
Wang P, Dong Q, Zhang C, Kuan PF, Liu Y, Jeck WR, Andersen JB, Jiang W, Savich GL, Tan TX, et al: Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene. 32:3091–3100. 2013. View Article : Google Scholar | |
Xu YF, Liu HD, Liu ZL, Pan C, Yang XQ, Ning SL, Zhang ZL, Guo S and Yu JM: Sprouty2 suppresses progression and correlates to favourable prognosis of intrahepatic cholangiocar-cinoma via antagonizing FGFR2 signalling. J Cell Mol Med. 22:5596–5606. 2018. View Article : Google Scholar : PubMed/NCBI | |
Mazzaferro V, El‑Rayes BF, Droz Dit Busset M, Cotsoglou C, Harris W P, Damjanov N, Masi G, Rimassa L, Personeni N, Braiteh F, et al: Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangio-carcinoma. Br J Cancer. 120:165–171. 2019. View Article : Google Scholar | |
Sheng Y, Wei J, Zhang Y, Gao X, Wang Z, Yang J, Yan S, Zhu Y, Zhang Z, Xu D, et al: Mutated EPHA2 is a target for combating lymphatic metastasis in intrahepatic cholangiocarcinoma. Int J Cancer. 144:2440–2452. 2019. View Article : Google Scholar | |
Tian XP, Wang CY, Jin XH, Li M, Wang FW, Huang WJ, Yun JP, Xu RH, Cai QQ and Xie D: Acidic microenvironment up‑regu-lates exosomal miR-21 and miR-10b in early-stage hepatocellular carcinoma to promote cancer cell proliferation and metastasis. Theranostics. 9:1965–1979. 2019. View Article : Google Scholar : | |
Amr KS, Elmawgoud Atia HA, Elazeem Elbnhawy RA and Ezzat WM: Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma. Genes Dis. 4:215–221. 2017. View Article : Google Scholar | |
Wang L, Sun L, Wang Y, Yao B, Liu R, Chen T, Tu K, Liu Q and Liu Z: MiR-1204 promotes hepatocellular carcinoma progression through activating MAPK and c-Jun/AP1 signaling by targeting ZNF418. Int J Biol Sci. 15:pp. 1514–1522. 2019, View Article : Google Scholar : PubMed/NCBI | |
Ji J, Rong Y, Luo CL, Li S, Jiang X, Weng H, Chen H, Zhang WW, Xie W and Wang FB: Up-regulation of hsa-miR-210 promotes venous metastasis and predicts poor prognosis in hepatocellular carcinoma. Front Oncol. 8:5692018. View Article : Google Scholar : PubMed/NCBI | |
Li F, Wang F, Zhu C, Wei Q, Zhang T and Zhou YL: MiR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker. Int J Nanomedicine. 13:2295–2307. 2018. View Article : Google Scholar : PubMed/NCBI | |
Li H, Zhou ZQ, Yang ZR, Tong DN, Guan J, Shi BJ, Nie J, Ding XT, Li B, Zhou GW and Zhang ZY: MicroRNA‑191 acts as a tumor promoter by modulating the TET1-p53 pathway in intrahepatic cholangiocarcinoma. Hepatology. 66:136–151. 2017. View Article : Google Scholar : PubMed/NCBI | |
Wu J, Yang B, Zhang Y, Feng X, He B, Xie H, Zhou L, Wu J and Zheng S: MiR-424-5prepresses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5. Int J Biol Sci. 15:pp. 1591–1599. 2019, View Article : Google Scholar : | |
Marisi G, Cucchetti A, Ulivi P, Canale M, Cabibbo G, Solaini L, Foschi FG, De Matteis S, Ercolani G, Valgiusti M, et al: Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers. World J Gastroenterol. 24:4152–4163. 2018. View Article : Google Scholar : PubMed/NCBI | |
Shao Q, Ren P, Li Y, Peng B, Dai L, Lei N, Yao W, Zhao G, Li L and Zhang J: Autoantibodies against glucose‑regulated protein 78 as serological diagnostic biomarkers in hepatocellular carcinoma. Int J Oncol. 41:1061–1067. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chiou JF, Tai CJ, Huang MT, Wei PL, Wang YH, An J, Wu CH, Liu TZ and Chang YJ: Glucose‑regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocel-lular carcinoma. Ann Surg Oncol. 17:pp. 603–612. 2010, View Article : Google Scholar | |
Li R, Yanjiao G and Wubin H: Secreted GRP78 activates EGFR‑SRC‑STAT3 signaling and confers the resistance to sora-feinib in HCC cells. Oncotarget. 8:19354–19364. 2017. View Article : Google Scholar : PubMed/NCBI | |
Hu H, Gao L, Wang C, Li Y, Ma H, Chen L, Qin J, Liu B, Liu Y and Liang C: Lower serum soluble-EGFR is a potential biomarker for metastasis of HCC demonstrated by N-glycoproteomic analysis. Discov Med. 19:333–341. 2015.PubMed/NCBI | |
Ezzoukhry Z, Louandre C, Trécherel E, Godin C, Chauffert B, Dupont S, Diouf M, Barbare JC, Mazière JC and Galmiche A: EGFR activation is a potential determinant of primary resistance of hepatocellular carcinoma cells to sorafenib. Int J Cancer. 131:2961–2969. 2012. View Article : Google Scholar : PubMed/NCBI | |
Komposch K and Sibilia M: EGFR signaling in liver diseases. Int J Mol Sci. 17:pii: E30. 2015, View Article : Google Scholar | |
Firtina Karagonlar Z, Koc D, Iscan E, Erdal E and Atabey N: Elevated hepatocyte growth factor expression as an autocrine c-Met activation mechanism in acquired resistance to sorafenib in hepatocellular carcinoma cells. Cancer Sci. 107:pp. 407–416. 2016, View Article : Google Scholar : PubMed/NCBI | |
Xiang Q, Chen W, Ren M, Wang J, Zhang H, Deng DY, Zhang L, Shang C and Chen Y: Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET. Clin Cancer Res. 20:pp. 2959–2970. 2014, View Article : Google Scholar : PubMed/NCBI | |
Han P, Li H, Jiang X, Zhai B, Tan G, Zhao D, Qiao H, Liu B, Jiang H and Sun X: Dual inhibition of Akt and c‑Met as a second-line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells. Mol Oncol. 11:320–334. 2017. View Article : Google Scholar : PubMed/NCBI | |
Capurro M, Martin T, Shi W and Filmus J: Glypican‑3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling. J Cell Sci. 127:pp. 1565–1575. 2014, View Article : Google Scholar : PubMed/NCBI | |
Austinat M, Dunsch R, Wittekind C, Tannapfel A, Gebhardt R and Gaunitz F: Correlation between beta-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma. Mol Cancer. 7:212008. View Article : Google Scholar : PubMed/NCBI | |
Lachenmayer A, Alsinet C, Savic R, Cabellos L, Toffanin S, Hoshida Y, Villanueva A, Minguez B, Newell P, Tsai H W, et al: Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib. Clin Cancer Res. 18:4997–5007. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hu CT, Wu JR, Cheng CC and Wu WS: The therapeutic targeting of HGF/c-Met signaling in hepatocellular carcinoma: Alternative approaches. Cancers (Basel). 9. pii: E58. 2017, View Article : Google Scholar | |
Gao W, Kim H and Ho M: Human monoclonal antibody targeting the heparan sulfate chains of glypican-3 inhibits HGF-mediated migration and motility of hepatocellular carcinoma cells. PLoS One. 10:e01376642015. View Article : Google Scholar : PubMed/NCBI | |
Yu J, Yuan X, Sjöholm L, Liu T, Kong F, Ekström TJ, Björkholm M and Xu D: Telomerase reverse transcriptase regulates DNMT3B expression/aberrant DNA methylation phenotype and AKT activation in hepatocellular carcinoma. Cancer Lett. 434:33–41. 2018. View Article : Google Scholar : PubMed/NCBI | |
Wang S, Zhu M, Wang Q, Hou Y, Li L, Weng H, Zhao Y, Chen D, Ding H, Guo J and Li M: Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signaling. Cell Death Dis. 10:pp. 832019, View Article : Google Scholar | |
Meng X, Franklin DA, Dong J and Zhang Y: MDM2‑p53 pathway in hepatocellular carcinoma. Cancer Res. 74:7161–7167. 2014. View Article : Google Scholar : PubMed/NCBI |