ABSTRACT
BACKGROUND: There is conflicting data in the literature about the association of ABO blood type and susceptibility to COVID-19 infection. Moreover, very few studies have examined the effect of blood type on severity of COVID-19 infection. METHODS: This was a retrospective, single-center analysis of adult patients with COVID-19 infection who were hospitalized between March 8th to July 31st, 2020 at a regional tertiary care hospital. All patients who were hospitalized with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection and had a documented ABO blood type were enrolled in this analysis. Aims of this study were to examine the prevalence of ABO blood types in patients with COVID-19 infection and to determine the frequency of severe COVID-19 infection among ABO blood types. RESULTS: A total of 227 cases were identified. Our cohort had a mean age of 63.3 years and 60% were males. The most common blood type was O (49%) followed by A (36%), which was similar to the prevalence of ABO blood types in our regional population. Moreover, there was no significant difference in the frequency of severe COVID-19 infection between ABO blood types (O: 50%, A: 53%, B: 56%, AB: 57%; P=0.93), or any additional outcomes including in-hospital mortality rate (P=0.72), need for ICU admission (P=0.66), ICU free days at day 28 (P=0.51), hospital free days at day 28 (P=0.43), or need for acute renal replacement therapy (P=0.09). CONCLUSION: We did not find an increased susceptibility of any blood type to COVID-19 infection, nor was there an increased risk of severe COVID-19 infection in any ABO blood types.
ABSTRACT
Advanced breast cancers preferentially metastasize to bone where cells in the bone microenvironment produce factors that enhance breast cancer cell homing and growth. Expression of the ubiquitin E3 ligase WWP1 is increased in some breast cancers, but its role in bone metastasis has not been investigated. Here, we studied the effects of WWP1 and itch, its closest family member, on breast cancer bone metastasis. First, we immunostained a multi-tumor tissue microarray and a breast cancer tissue microarray and demonstrated that WWP1 and ITCH are expressed in some of breast cancer cases. We then knocked down WWP1 or itch in MDA-MB-231 breast cancer cells using shRNA and inoculated these cells and control cells into the left ventricle of athymic nude mice. Radiographs showed that mice given shWWP1 cells had more osteolytic lesions than mice given control MDA-MB-231 cells. Histologic analysis confirmed osteolysis and showed significantly increased tumor area in bone marrow of the mice. WWP1 knockdown did not affect cell growth, survival or osteoclastogenic potential, but markedly increased cell migration toward a CXCL12 gradient in vitro. Furthermore, WWP1 knockdown significantly reduced CXCL12-induced CXCR4 lysosomal trafficking and degradation. In contrast, itch knockdown had no effect on MDA-MB-231 cell bone metastasis. Taken together, these findings demonstrate that WWP1 negatively regulates cell migration to CXCL12 by limiting CXCR4 degradation to promote breast cancer metastasis to bone and highlight the potential utility of WWP1 as a prognostic indicator for breast cancer bone metastasis.
Subject(s)
Bone Neoplasms/secondary , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Cell Movement/drug effects , Chemokine CXCL12/pharmacology , Ubiquitin-Protein Ligases/metabolism , Animals , Apoptosis/drug effects , Bone Neoplasms/complications , Bone Neoplasms/pathology , Breast Neoplasms/complications , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Gene Knockdown Techniques , Humans , Lysosomes/drug effects , Lysosomes/metabolism , Mice , Mice, Nude , Middle Aged , Osteolysis/complications , Osteolysis/pathology , Protein Transport/drug effects , RNA, Small Interfering/metabolism , Receptors, CXCR4/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Repressor Proteins/metabolism , Tissue Array AnalysisABSTRACT
The molecular classification for breast carcinomas has been used in clinical studies with a simple surrogate panel of immunohistochemistry (IHC) markers. The objective of this current project was to study the molecular classification of commonly used breast cancer cell lines by IHC analysis. Seventeen breast cancer cell lines were harvested, fixed in formalin and made into cell blocks. IHC analyses were performed on each cell block with antibodies to estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, CK5/6, Ki-67 and androgen receptor (AR). Among the 17 cell lines, MCF-7 and ZR-75-1 fell to Luminal A subtype; BT-474 to Luminal B subtype; SKBR-3, MDA-MD-435 and AU 565 to HER2 over-expression subtype; MDA-MB-231, MCF-12A, HBL 101, HS 598 T, MCF-10A, MCF-10F, BT-20, 468 and BT-483 to basal subtype. MDA-MB-453 belonged to Unclassified subtype. Since each subtype defined by this IHC-based molecular classification does show a distinct clinical outcome, attention should be paid when choosing a cell line for any study.
