Analysis of gene family expression in African endemic- and AIDS-related Kaposi's sarcoma

Kaposi's sarcoma (KS) is subdivided into four epidemiological variants, all of which have in common a similar histopathology and expression of human herpes virus 8 (HHV-8) in the lesions. Two forms are associated with immune suppression, post-transplant KS and AIDS-related KS, while the two others, classic KS and African endemic KS are not. HHV-8 infections are normally benign, with the incidence of HHV-8 infection being much higher than the incidence of KS. The cellular deregulation that leads to the formation of KS lesions is poorly understood, as is the infected cell type. It is also unknown whether gene expression patterns are similar between the epidemiological forms, especially as two forms are not associated with immune dysfunction. To gain insight into the genes expressed in KS lesions, we have generated Serial Analysis of Gene Expression (SAGE) libraries from both AIDS-KS and African endemic KS tissue to analyze mRNA levels in KS. The SAGE libraries were compared with each other and with libraries in the SAGEmap database. Systematic analysis of the level of gene expression of twelve specific gene families or related genes, including HHV-8 genes, was performed for both endemic KS and AIDS-KS tissue. The results suggested that endemic KS and AIDS-KS have a similar pattern of gene expression, in line with their comparable histopathology. High or very high expression was found in KS compared with other libraries for psoriasin, HLA-C, complement component 1, keratin 16, galectin 9, plexin D1, CD51, CD31, CCL18, CCL19, CCL21, and many other genes. In general, not the tag counts but rather the tag count ratio of KS versus other libraries gave information about the level of gene expression. Interestingly, a few genes were overexpressed in AIDS-KS compared with endemic KS (e.g. Von Willebrand Factor, D component of complement), while others were overexpressed in endemic KS (e.g. HLA-F, MMP-12, CD74, calgranulin-A). It has been suggested that iron is an important factor in the establishment of KS. Analysis of iron-related gene expression in KS, however, suggested no clear abnormalities. Relatively high expression was only found for the light polypeptide of ferritin, and heme oxygenase-1, and intermediate expression was seen for the hemoglobin scavenger receptor CD163, compatible with macrophage-related iron-uptake as erythrocytes leak from abnormal vessels in the KS lesions. In conclusion, the comparison of gene family expression in KS SAGE libraries has provided new insights into the molecular mechanism involved in the pathogenesis of KS.