ABSTRACT
The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues. HIGHLIGHTSO_LICharacterization of 5336 regulated proteins out of 11,394 quantified proteins in the lung, spleen, liver, kidney, heart, thyroid and testis autopsies from 19 patients died from COVID-19. C_LIO_LICTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. C_LIO_LIEvidence for suppression of glucose metabolism in the spleen, liver and kidney; suppression of fatty acid metabolism in the kidney; enhanced fatty acid metabolism in the lung, spleen, liver, heart and thyroid from COVID-19 patients; enhanced protein translation initiation in the lung, liver, renal medulla and thyroid. C_LIO_LITentative model for multi-organ injuries in patients died from COVID-19: SARS-CoV-2 infection triggers hyperinflammatory which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart, kidney and thyroid. C_LIO_LITesticular injuries in COVID-19 patients included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. C_LI
ABSTRACT
Purpose To study the clinicalpathologic features,diagnosis,differential diagnosis and prognosis of cervical adenoid basal carcinoma (ABC) for improving further recognition and avoiding the likelihood of unnecessarily aggressive treatment to this disease.Methods Clinical presentations and pathological features of 4 cases of cervical ABC were analyzed by hematoxylin and eosin staining,immunohistochemical EnVision staining and in situ hybridization technology.The relevant literatures were reviewed.Results The age of 4 cases with cervical ABC ranged from 53 to 67 years (mean:61.5 years).All of the 4 patients underwent hysterectomy with bilateral salpingo-oophorectomy.Microscopically,the tumors were composed of small,well-differentiated and uniform basaloid cells and the tumor cells formed rounded nests or cords.The tumor cells arranged in palisading at the periphery of the nests.Some of the nests had central cystic spaces and there may also be focal glandular or squamous differentiation in the centre of the nests.Cervical intraepithelial neoplasia (CIN) lesions were observed in all 4 cases.Immunohistochemically,all the tumor cells were negative for CK7,ER,CEA,CD117 and S-100,while CK5/6,CK8/18,CK19,p16,p53,BCL-2 and p63 were positive.HPV 16/18 DNA were positive by in situ hybridization.The patients remained alive without recurrence and metastasis after follow-up 19 to 62 months.Conclusion ABC of the uterine cervix is a rare neoplasm with excellent prognosis.Differentiation of ABC from adenoid cystic carcinoma,basaloid squamous carcinoma,neuroendocrine carcinoma and adenosquamous carcinoma is important due to their different prognosis.Treatment is predominantly hysterectomy or laser electrocantery excision procedure (Leep).Radiotherapy or chemotherapy is not recommeded.
