Int J Biol Sci 2021; 17(3):897-910. doi:10.7150/ijbs.54055

Research Paper

Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19

Jiewen Fu1*, Chunli Wei1*, Jiayue He1*, Lianmei Zhang2*, Ju Zhou1, Kyathegowdanadoddi Srinivasa Balaji3, Shiyi Shen1, Jiangzhou Peng4✉, Amrish Sharma5✉, Junjiang Fu1✉

1. Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan, China.
2. Department of Pathology, the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu, China.
3. PG Department of Biotechnology, Teresian College, University of Mysore, Mysore 570011, Karnataka, India.
4. Department of Thoracic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China.
5. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
*Equal contributions

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Citation:
Fu J, Wei C, He J, Zhang L, Zhou J, Balaji KS, Shen S, Peng J, Sharma A, Fu J. Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19. Int J Biol Sci 2021; 17(3):897-910. doi:10.7150/ijbs.54055. Available from https://www.ijbs.com/v17p0897.htm

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Abstract

HSPA5 (BiP, GRP78) has been reported as a potential host-cell receptor for SARS-Cov-2, but its expression profiles on different tissues including tumors, its susceptibility to SARS-Cov-2 virus and severity of its adverse effects on malignant patients are unclear. In the current study, HSPA5 has been found to be expressed ubiquitously in normal tissues and significantly increased in 14 of 31 types of cancer tissues. In lung cancer, mRNA levels of HSPA5 were 253-fold increase than that of ACE2. Meanwhile, in both malignant tumors and matched normal samples across almost all cancer types, mRNA levels of HSPA5 were much higher than those of ACE2. Higher expression of HSPA5 significantly decreased patient overall survival (OS) in 7 types of cancers. Moreover, systematic analyses found that 7.15% of 5,068 COVID-19 cases have malignant cancer coincidental situations, and the rate of severe events of COVID-19 patients with cancers present a higher trend than that for all COVID-19 patients, showing a significant difference (33.33% vs 16.09%, p<0.01). Collectively, these data imply that the tissues with high HSPA5 expression, not low ACE2 expression, are susceptible to be invaded by SARS-CoV-2. Taken together, this study not only indicates the clinical significance of HSPA5 in COVID-19 disease and cancers, but also provides potential clues for further medical treatments and managements of COVID-19 patients.

Keywords: cancer, HSPA5, prognostics, SARS-CoV-2, transcriptomics.