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

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...

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Autores principales: Hao, Chengcheng, Cui, Yuxin, Lane, Jane, Jia, Shuqin, Ji, Jiafu, Jiang, Wen G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305399/
https://www.ncbi.nlm.nih.gov/pubmed/34359989
http://dx.doi.org/10.3390/cells10071820
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author Hao, Chengcheng
Cui, Yuxin
Lane, Jane
Jia, Shuqin
Ji, Jiafu
Jiang, Wen G.
author_facet Hao, Chengcheng
Cui, Yuxin
Lane, Jane
Jia, Shuqin
Ji, Jiafu
Jiang, Wen G.
author_sort Hao, Chengcheng
collection PubMed
description 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.
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spelling pubmed-83053992021-07-25 Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer Hao, Chengcheng Cui, Yuxin Lane, Jane Jia, Shuqin Ji, Jiafu Jiang, Wen G. Cells Article 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. MDPI 2021-07-19 /pmc/articles/PMC8305399/ /pubmed/34359989 http://dx.doi.org/10.3390/cells10071820 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hao, Chengcheng
Cui, Yuxin
Lane, Jane
Jia, Shuqin
Ji, Jiafu
Jiang, Wen G.
Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer
title Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer
title_full Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer
title_fullStr Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer
title_full_unstemmed Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer
title_short Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer
title_sort distinctive prognostic value and cellular functions of osteopontin splice variants in human gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305399/
https://www.ncbi.nlm.nih.gov/pubmed/34359989
http://dx.doi.org/10.3390/cells10071820
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