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.

中文翻译：

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正常个体和患有 COVID-19 的癌症患者中 HSPA5 (GRP78) 表达谱的评估和表征

HSPA5（BiP、GRP78）已被报道为 SARS-Cov-2 的潜在宿主细胞受体，但其在包括肿瘤在内的不同组织中的表达谱、其对 SARS-Cov-2 病毒的易感性及其对恶性肿瘤的不良影响的严重程度患者不清楚。目前的研究发现，HSPA5在正常组织中普遍表达，并在31种癌组织中的14种中显着增加。在肺癌中，HSPA5的mRNA水平比ACE2增加了253倍。同时，在几乎所有癌症类型的恶性肿瘤和匹配的正常样本中，HSPA5的mRNA水平远高于ACE2的mRNA水平。HSPA5的较高表达显着降低了 7 种癌症患者的总生存期 (OS)。此外，系统分析发现，5,068例COVID-19病例中，有7.15%存在恶性肿瘤巧合情况，且患有癌症的COVID-19患者的严重事件发生率呈现出高于所有COVID-19患者的严重事件发生率的趋势，表现出显着差异（33.33% vs 16.09%，p <0.01）。总的来说，这些数据表明，HSPA5 高表达的组织（而非 ACE2 表达低的组织）更容易受到 SARS-CoV-2 的侵袭。总而言之，这项研究不仅表明了 HSPA5 在 COVID-19 疾病和癌症中的临床意义，而且为 COVID-19 患者的进一步医疗和管理提供了潜在的线索。