Down-regulation of TRPV6 Is Associated With Adverse Prognosis in Hepatocellular Carcinoma Treated With Curative Resection

被引:4
作者
Koh, Hyun Hee [1 ]
Choi, Sangjoon [1 ]
Park, Cheol-Keun [1 ,2 ]
Ha, Sang Yun [1 ]
机构
[1] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Pathol & Translat Genom, 81 Irwon Ro, Seoul 06351, South Korea
[2] Seegene Med Fdn, Anat Pathol Reference Lab, Seoul, South Korea
关键词
Hepatocellular carcinoma; prognosis; recurrence; TRPV6; biomarkers; CALCIUM-CHANNEL; PROSTATE-CANCER; CATION CHANNEL; EXPRESSION; RECURRENCE; SORAFENIB; GROWTH; CAT1;
D O I
10.21873/cgp.20318
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: Transient receptor potential vanilloid 6 (TRPV6), an endothelial Ca2+-selective entry channel, is expressed in various cancer types, and a selective TRPV6 inhibitor is currently being investigated in a clinical trial. However, TRPV6 expression in hepatocellular carcinoma (HCC) has not been reported. Materials and Methods: We evaluated TRPV6 expression in 219 cases of HCC and analyzed its association with clinicopathological parameters and prognostic significance. TRPV6 mRNA expression was compared between HCC and non-tumor liver tissues using various public datasets, and its prognostic effect was examined in The Cancer Genome Atlas (TCGA) cohort. Results: Low TRPV6 expression was found in 37.4% of patients, which was significantly associated with adverse histologic features, and patients with low TRPV6 expression had shorter recurrence-free and disease free survival. TRPV6 mRNA expression was consistently lower in HCC compared to non-tumor liver samples in public datasets, at the whole tissue level as well as single-cell level. Patients with low TRPV6 expression in the TCGA cohort had shorter progression free survival. Conclusion: TRPV6 expression is down-regulated in HCCs and associated with a poor prognosis. TRPV6 may be a prognostic biomarker in HCC.
引用
收藏
页码:259 / 269
页数:11
相关论文
共 41 条
[31]   TRPV Channels in Tumor Growth and Progression [J].
Santoni, Giorgio ;
Farfariello, Valerio ;
Amantini, Consuelo .
TRANSIENT RECEPTOR POTENTIAL CHANNELS, 2011, 704 :947-967
[32]   Barrier to autointegration factor 1, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, and splicing factor 3b subunit 4 as early-stage cancer decision markers and drivers of hepatocellular carcinoma [J].
Shen, Qingyu ;
Eun, Jung Woo ;
Lee, Kyungbun ;
Kim, Hyung Seok ;
Yang, Hee Doo ;
Kim, Sang Yean ;
Lee, Eun Kyung ;
Kim, Taemook ;
Kang, Keunsoo ;
Kim, Seongchan ;
Min, Dal-Hee ;
Oh, Soon-Nam ;
Lee, Young-Joon ;
Moon, Hyuk ;
Ro, Simon Weonsang ;
Park, Won Sang ;
Lee, Jung Young ;
Nam, Suk Woo .
HEPATOLOGY, 2018, 67 (04) :1360-1377
[33]   Recurrence of Hepatocellular Carcinoma [J].
Sherman, Morris .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (19) :2045-2047
[34]   Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study [J].
Villa, Erica ;
Critelli, Rosina ;
Lei, Barbara ;
Marzocchi, Guido ;
Camma, Calogero ;
Giannelli, Gianluigi ;
Pontisso, Patrizia ;
Cabibbo, Giuseppe ;
Enea, Marco ;
Colopi, Stefano ;
Caporali, Cristian ;
Pollicino, Teresa ;
Milosa, Fabiola ;
Karampatou, Aimilia ;
Todesca, Paola ;
Bertolini, Elena ;
Maccio, Livia ;
Luz Martinez-Chantar, Maria ;
Turola, Elena ;
Del Buono, Mariagrazia ;
De Maria, Nicola ;
Ballestri, Stefano ;
Schepis, Filippo ;
Loria, Paola ;
Gerunda, Giorgio Enrico ;
Losi, Luisa ;
Cillo, Umberto .
GUT, 2016, 65 (05) :861-869
[35]   TRPV6 and prostate cancer:: cancer growth beyond the prostate correlates with increased TRPV6 Ca2+ channel expression [J].
Wissenbach, U ;
Niemeyer, B ;
Himmerkus, N ;
Fixemer, T ;
Bonkhoff, H ;
Flockerzi, V .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 322 (04) :1359-1363
[36]   Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer [J].
Wissenbach, U ;
Niemeyer, BA ;
Fixemer, T ;
Schneidewind, A ;
Trost, C ;
Cavalié, A ;
Reus, K ;
Meese, E ;
Bonkhoff, H ;
Flockerzi, V .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (22) :19461-19468
[37]   Decreased Expression of the Epithelial Ca2+ Channel TRPV5 and TRPV6 in Human Renal Cell Carcinoma Associated With Vitamin D Receptor [J].
Wu, Yongyang ;
Miyamoto, Tatsuya ;
Li, Kai ;
Nakagomi, Hiroshi ;
Sawada, Norifumi ;
Kira, Satoru ;
Kobayashi, Hideki ;
Zakohji, Hidenori ;
Tsuchida, Takayuki ;
Fukazawa, Mizuya ;
Araki, Isao ;
Takeda, Masayuki .
JOURNAL OF UROLOGY, 2011, 186 (06) :2419-2425
[38]   Inhibition of Transient Receptor Potential Vanilloid 6 channel, elevated in human ovarian cancers, reduces tumour growth in a xenograft model [J].
Xue, Hui ;
Wang, Yuzhuo ;
MacCormack, Tyson J. ;
Lutes, Tyler ;
Rice, Christopher ;
Davey, Michelle ;
Dugourd, Dominique ;
Ilenchuk, T. Toney ;
Stewart, John M. .
JOURNAL OF CANCER, 2018, 9 (17) :3196-3207
[39]   TRPV6 plays a new role in predicting survival of patients with esophageal squamous cell carcinoma [J].
Zhang, Shui-Shen ;
Xie, Xuan ;
Wen, Jing ;
Luo, Kong-Jia ;
Liu, Qian-wen ;
Yang, Hong ;
Hu, Yi ;
Fu, Jian-Hua .
DIAGNOSTIC PATHOLOGY, 2016, 11
[40]   Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial [J].
Zhu, Andrew X. ;
Finn, Richard S. ;
Edeline, Julien ;
Cattan, Stephane ;
Ogasawara, Sadahisa ;
Palmer, Daniel ;
Verslype, Chris ;
Zagonel, Vittorina ;
Fartoux, Laetitia ;
Vogel, Arndt ;
Sarker, Debashis ;
Verset, Gontran ;
Chan, Stephen L. ;
Knox, Jennifer ;
Daniele, Bruno ;
Webber, Andrea L. ;
Ebbinghaus, Scot W. ;
Ma, Junshui ;
Siegel, Abby B. ;
Cheng, Ann-Lii ;
Kudo, Masatoshi .
LANCET ONCOLOGY, 2018, 19 (07) :940-952