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Article

Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

by 1,2,†, 2,†, 2, 3, 3 and 2,*
1
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
2
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK
3
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, No. 52, Beijing 100142, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to the study.
Academic Editors: Daniela Spano and Giuseppina Comito
Cells 2021, 10(7), 1820; https://doi.org/10.3390/cells10071820
Received: 9 June 2021 / Revised: 14 July 2021 / Accepted: 15 July 2021 / Published: 19 July 2021
Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer. View Full-Text
Keywords: osteopontin; OPN splice variants; gastric cancer; prognosis; biological function; chemoresistance osteopontin; OPN splice variants; gastric cancer; prognosis; biological function; chemoresistance
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MDPI and ACS Style

Hao, C.; Cui, Y.; Lane, J.; Jia, S.; Ji, J.; Jiang, W.G. Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer. Cells 2021, 10, 1820. https://doi.org/10.3390/cells10071820

AMA Style

Hao C, Cui Y, Lane J, Jia S, Ji J, Jiang WG. Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer. Cells. 2021; 10(7):1820. https://doi.org/10.3390/cells10071820

Chicago/Turabian Style

Hao, Chengcheng, Yuxin Cui, Jane Lane, Shuqin Jia, Jiafu Ji, and Wen G. Jiang. 2021. "Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer" Cells 10, no. 7: 1820. https://doi.org/10.3390/cells10071820

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