Pan‑cancer analysis of transmembrane protease serine 2 and cathepsin L that mediate cellular SARS‑CoV‑2 infection leading to COVID-19.
泛癌分析介导细胞sars ‑ cov ‑ 2 感染导致新型冠状病毒肺炎的跨膜蛋白酶丝氨酸 2 和组织蛋白酶L。
- 作者列表："Katopodis P","Anikin V","Randeva HS","Spandidos DA","Chatha K","Kyrou I","Karteris E
:Severe acute respiratory syndrome (SARS) coronavirus‑2 (SARS‑CoV2) is the cause of a new disease (COVID‑19) which has evolved into a pandemic during the first half of 2020. Older age, male sex and certain underlying diseases, including cancer, appear to significantly increase the risk for severe COVID‑19. SARS‑CoV‑2 infection of host cells is facilitated by the angiotensin‑converting enzyme 2 (ACE‑2), and by transmembrane protease serine 2 (TMPRSS2) and other host cell proteases such as cathepsin L (CTSL). With the exception of ACE‑2, a systematic analysis of these two other SARS‑CoV2 infection mediators in malignancies is lacking. Here, we analysed genetic alteration, RNA expression, and DNA methylation of TMPRSS2 and CTSL across a wide spectrum of tumors and controls. TMPRSS2 was overexpressed in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), uterine corpus endometrial carcinoma and uterine carcinosarcoma, with PRAD and READ exhibiting the highest expression of all cancers. CTSL was upregulated in lymphoid neoplasm diffuse large B‑cell lymphoma, oesophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lower grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, and thymoma. Hypo‑methylation of both genes was evident in most cases where they have been highly upregulated. We have expanded on our observations by including data relating to mutations and copy number alterations at pan‑cancer level. The novel hypotheses that are stemming out of these data need to be further investigated and validated in large clinical studies.
: 严重急性呼吸综合征 (传染性非典型肺炎) 冠状病毒 ‑ 2 传染性非典型肺炎 ‑ CoV2) 是一种新疾病 (covid ‑ 19) 的病因，该疾病已在 2020 年上半年演变为大流行。年龄较大、男性和某些基础疾病 (包括癌症) 似乎会显著增加重度covid ‑ 19 的风险。Sars ‑ cov ‑ 2 感染宿主细胞由血管紧张素转化酶 2 (ace ‑ 2) 和跨膜蛋白酶丝氨酸 2 (TMPRSS2) 和其他宿主细胞蛋白酶如组织蛋白酶L (CTSL) 促进。除ace ‑ 2 外，缺乏对这两种其他sars ‑ CoV2 感染介质在恶性肿瘤中的系统分析。在此，我们分析了TMPRSS2 和CTSL在广泛肿瘤和对照中的遗传改变、RNA表达和DNA甲基化。TMPRSS2 在宫颈鳞癌和宫颈腺癌、结肠腺癌、前列腺腺癌 (PRAD) 、直肠腺癌 (READ) 、子宫内膜样癌和子宫癌肉瘤中过表达，PRAD和READ表现出所有癌症中最高的表达。CTSL在淋巴肿瘤弥漫性大b ‑ 细胞淋巴瘤、食管癌、多形性胶质母细胞瘤、头颈部鳞状细胞癌、低度恶性胶质瘤、胰腺癌、皮肤黑色素瘤、胃腺癌、和胸腺瘤。这两个基因的低甲基化在大多数高度上调的情况下是明显的。我们通过包括与癌症水平的突变和拷贝数改变相关的数据来扩展我们的观察。这些数据产生的新假设需要在大型临床研究中进一步研究和验证。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.