Background There is increasing interest in hepatocellular carcinomas (HCC) expressing “stemness”-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of “stemness.” Methods: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. Results: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). Conclusions: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression.
Citations
Citations to this article as recorded by
Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters? Caecilia HC Sukowati, Korri El-Khobar, Chyntia Olivia Maurine Jasirwan, Juferdy Kurniawan, Rino Alvani Gani Annals of Hepatology.2024; 29(1): 101153. CrossRef
Research progress and prospects of AFP-positive gastric cancer Long Zhao, Changjiang Yang, Yilin Lin, Shan Wang, Yingjiang Ye, Zhanlong Shen Foregut Surgery.2022; 2(1): 29. CrossRef
SALL4 and microRNA: The Role of Let-7 Jun Liu, Madeline A. Sauer, Shaza G. Hussein, Junyu Yang, Daniel G. Tenen, Li Chai Genes.2021; 12(9): 1301. CrossRef
Hepatoid Teratoma, Hepatoid Yolk Sac Tumor, and Hepatocellular Carcinoma Khaleel I. Al-Obaidy, Sean R. Williamson, Nathan Shelman, Muhammad T. Idrees, Thomas M. Ulbright American Journal of Surgical Pathology.2021; 45(1): 127. CrossRef
Targeting an Inducible SALL4-Mediated Cancer Vulnerability with Sequential Therapy Junyu Yang, Chong Gao, Miao Liu, Yao-Chung Liu, Junsu Kwon, Jun Qi, Xi Tian, Alicia Stein, Yanjing V. Liu, Nikki R. Kong, Yue Wu, Shenyi Yin, Jianzhong Xi, Zhiyuan Chen, Kalpana Kumari, Hannan Wong, Hongbo Luo, Leslie E. Silberstein, Julie A.I. Thoms, Ash Cancer Research.2021; 81(23): 6018. CrossRef
Lipoprotein‐Like Nanoparticle Carrying Small Interfering RNA Against Spalt‐Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden William Cruz, Huang Huang, Brian Barber, Elisa Pasini, Lili Ding, Gang Zheng, Juan Chen, Mamatha Bhat Hepatology Communications.2020; 4(5): 769. CrossRef
Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features Yakun Wang, Li Sun, Zhongwu Li, Jing Gao, Sai Ge, Cheng Zhang, Jiajia Yuan, Xicheng Wang, Jian Li, Zhihao Lu, Jifang Gong, Ming Lu, Jun Zhou, Zhi Peng, Lin Shen, Xiaotian Zhang Gastric Cancer.2019; 22(6): 1183. CrossRef
Gynecologic Serous Carcinoma: An Immunohistochemical Analysis of Malignant Body Fluid Specimens Shuyue Ren, William Klump Archives of Pathology & Laboratory Medicine.2019; 143(6): 677. CrossRef
The Pluripotency Network in Colorectal Cancer Pathogenesis and Prognosis: an Update Ioannis A Voutsadakis Biomarkers in Medicine.2018; 12(6): 653. CrossRef
Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies Nuozhou Wang, Shanshan Wang, Ming-Yue Li, Bao-guang Hu, Li-ping Liu, Sheng-li Yang, Shucai Yang, Zhongqin Gong, Paul B. S. Lai, George G. Chen Therapeutic Advances in Medical Oncology.2018;[Epub] CrossRef
DNA demethylation induces SALL4 gene re-expression in subgroups of hepatocellular carcinoma associated with Hepatitis B or C virus infection H Fan, Z Cui, H Zhang, S K Mani, A Diab, L Lefrancois, N Fares, P Merle, O Andrisani Oncogene.2017; 36(17): 2435. CrossRef
Higher expression of SALL4 predicts poor cancer prognosis: A meta-analysis Hongyu Shen, Liangpeng Li, Dandan Wang, Sujin Yang, Xiu Chen, Siying Zhou, Shanliang Zhong, Jianhua Zhao, Jinhai Tang Cancer Biomarkers.2017; 19(4): 365. CrossRef
SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway Chuanjin Liu, Haibin Wu, Yanyan Li, Liang Shen, Renchun Yu, Hongwei Yin, Ting Sun, Chunming Sun, Youxin Zhou, Ziwei Du Journal of Neuro-Oncology.2017; 135(2): 263. CrossRef
Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells Germana Castelli, Elvira Pelosi, Ugo Testa Cancers.2017; 9(9): 127. CrossRef
Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis Lorenzo Nicolè, Tiziana Sanavia, Nicola Veronese, Rocco Cappellesso, Claudio Luchini, Paolo Dabrilli, Ambrogio Fassina Oncotarget.2017; 8(14): 22968. CrossRef
SALL4, the missing link between stem cells, development and cancer Hiro Tatetsu, Nikki R. Kong, Gao Chong, Giovanni Amabile, Daniel G. Tenen, Li Chai Gene.2016; 584(2): 111. CrossRef
A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer Soo Jeong Nam, Hyun Yang Yeo, Hee Jin Chang, Bo Hyun Kim, Eun Kyung Hong, Joong-Won Park Cancer Research and Treatment.2016; 48(4): 1229. CrossRef
Functional and clinical significance of SALL4 in breast cancer Ebubekir Dirican, Mustafa Akkiprik Tumor Biology.2016; 37(9): 11701. CrossRef
MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression Qinggang Tian, Yao Xiao, Yanting Wu, Yun Liu, Zhiqing Song, Wenfeng Gao, Jing Zhang, Jingling Yang, Yuguo Zhang, Tuankui Guo, Furong Dai, Zhigang Sun International Journal of Molecular Medicine.2016; 38(5): 1587. CrossRef
Oncogenic protein SALL4 and ZNF217 as prognostic indicators in solid cancers: a meta-analysis of individual studies Ji Cheng, Jinbo Gao, Xiaoming Shuai, Kaixiong Tao Oncotarget.2016; 7(17): 24314. CrossRef