ACE2 mRNA was found to be significantly over-expressed in the following types of cancer:

- colon adenocarcinoma (COAD)
- kidney renal papillary cell carcinoma (KIRP)
- pancreatic adenocarcinoma (PAAD)
- rectum adenocarcinoma (READ)
- stomach adenocarcinoma (STAD)

Over-expression of ACE2 in Cancer Tissue

ACE2 mRNA was found to be significantly under-expressed in the following types of cancer when compared against normal tissue:

- kidney chromophobe (KICH)
- sarcoma (SARC)
- testicular germ cell tumors (TGCT)
- thyroid carcinoma (THCA)

Under-expression of ACE2 in Cancer Tissue

Patients were divided into two groups: high ACE2 expression and low ACE2 expression.  The survival analysis was analyzed using a Kaplan-Meier plot.  No significant difference was observed in overall survival between the two expression level groups, but it was observed that patients with READ and STAD had more favorable outcomes in the high ACE2 expression group than the low expression group.  

- COAD: colon adenocarcinoma
- KIRP: kidney renal papillary cell carcinoma
- PAAD: pancreatic adenocarcinoma
- READ: rectum adenocarcinoma
- STAD: stomach adenocarcinoma
- KICH: kidney chromophobe
- SARC: sarcoma
- TGCT: testicular germ cell tumors
- THCA: thyroid carcinoma

Survival Prognosis of Patients with High/Low ACE2 Expression in Cancer Tissue

Data were obtained from the Gene Expression Profiling Interactive Analysis (GEPIA) based off of The Cancer Genome Atlas (TCGA).  Gene expression is reported as transcripts per kilobase  million (TPM).  Abbreviations used in the figure include:

- ACC. -  Adrenocortical  carcinoma
- BLCA  -  Bladder  Urothelial  Carcinoma
- BRCA  -  Breast  invasive  carcinoma
- CESC  - Cervical  squamous  cell  carcinoma  and  endocervical adenocarcinoma
- CHOL  - Cholangiocarcinoma
- COAD  -  Colon  adenocarcinoma
- DLBC  -  Lymphoid  Neoplasm Diffuse Large B-cell Lymphom
- ESCA - Esophageal carcinomaGBM - Glioblastoma multiforme
- HNSC - Head and Neck squamous cell carcinoma
- KICH  -  Kidney  Chromophobe
- KIRC  - Kidney  renal  clear  cell  carcinoma
- KIRP  - Kidney  renal papillary  cell  carcinoma
- LAML  -  Acute  Myeloid  Leukemia
- LGG  -  Brain  Lower  Grade Glioma
- LIHC -  Liver  hepatocellular carcinoma
- LUAD  -  Lung adenocarcinoma
- LUSC  - Lung  squamous  cell  carcinoma
- OV  -  Ovarian  serous  cystadenocarcinoma
- PAAD  - Pancreatic  adenocarcinoma
- PCPG  -  Pheochromocytoma  and  Paraganglioma
- PRAD  - Prostate adenocarcinoma
- READ - Rectum adenocarcinoma
- SARC – Sarcoma
- SKCM - Skin Cutaneous Melanoma
- STAD - Stomach adenocarcinoma
- TGCT - Testicular Germ Cell  Tumors
- THCA  -  Thyroid  carcinoma
- THYM  –  Thymoma;  UCEC  -  Uterine  Corpus Endometrial Carcinoma
- UCS - Uterine Carcinosarcoma

Comparing ACE2 and CD147 Expression in Cancer Tissue

According to the GEPIA dataset, nearly all cancer tissues can express ACE2 with renal cancer having the highest expression level.  Some cancerous tissues were found to have a significant increase in ACE2 when compared against the same noncancerous tissue.  

Michigan State University

- cancer tissue
- human airway epithelium tissue
- human brain expression
- protein and mRNA expression
- relationship to COVID-19

ACE2 Expression in Tissue and Organs

Ren, P., Gong, C., & Ma, S. (2020). Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients. Open Medicine, 15(1), 613-622.
https://www.degruyter.com/view/journals/med/15/1/article-p613.xml
doi: 10.1515/med-2020-0208 

Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients

One of the primary manifestations of COVID-19 is respiratory disease.  ACE2 expression was assessed in human airway epithelial tissue to better understand how SARS-CoV-2 interacts. with these cells. Studies included:

- ACE2 expression in healthy nonsmokers
- ACE2 expression in smokers
- ACE2 expression modulation by air pollution
- ACE2 expression modulated by miRNA (miR-1246)
- ACE2 expression in basal cells from the large and small airway epithelia of healthy nonsmokers

ACE2 Expression in Human Airway Epithelial Tissue

Cancer Tissue Expression of ACE2

Expression levels were determined using the HPA (https://www.proteinatlas.org).  Tissues that express ACE2 were broken down into five categories based off of the amount of ACE2 mRNA expression:

- (1, highest expression, score range: 122-10) small intestine, colon, duodenum, kidney, testis, gallbladder and heart muscle
- (2, medium high expression, score range: 5-1) adipose tissue, thyroid gland, epididymis, ductus deferens, breast, pancreas, rectum, ovary, esophagus, liver, seminal vesicle, salivary gland and placenta
- (3, medium low expression, score range: 0.9-0.5) vagina, lung, appendix, skeletal muscle, fallopian tube, lymph node, tongue, stomach and prostate
- (4, low expression, score range: 0.4-0.1) remaining tissues
- (5, no expression, score range: 0) parathyroid gland, bone marrow, monocytes, B-cells, NK-cells, dendritic cells and total peripheral blood mononuclear cell

ACE2 Protein and mRNA Expression in Tissue

ACE2 is known to be expressed in a variety of different tissues, including:

- Heart, kidneys, gastrointestinal (GI) tract, lungs, brain, testes, bladder, adipose tissue, vascular system, cholangiocytes (epithelial cells of the oral and nasal mucosa)

ACE2 expression may explain the SARS-CoV-2 organ localization.

Expression of ACE2 in Tissue and COVID-19

ACE2 expression was quantified in 21 regions of the human brain using multiple tissue expression (MTE) arrays (*p < 0.01 (ANOVA); error bars represent one standard deviation of the mean).  The highest expression was found in the pons, amygdala, and the medulla oblongata.  The pons and medulla oblongata are notably known to control breathing and respiration. 

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