APRIL is overexpressed in cancer: link with tumor progression

Abstract

Background: BAFF and APRIL share two receptors - TACI and BCMA - and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.

Methods: We compared the expression of BAFF, APRIL, TACI and BAFF-R gene expression in 40 human tumor types - brain, epithelial, lymphoid, germ cells - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.

Results: We found significant overexpression of TACI in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, BAFF and APRIL are overexpressed in many cancers and we show that APRIL expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.

Conclusion: Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.

Figure 1

BAFF expression in various cancers. BAFF gene expression in normal brain, glioblastoma multiforme [34-37], normal breast, breast carcinoma[40], normal esophagus, esophageal adenocarcinoma[41], normal kidney, renal carcinoma[42], normal testis, adult male germ cell tumor[43], Hodgkin lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma and follicular lymphoma[33]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.

Figure 2

APRIL expression in various cancers. APRIL gene expression in normal bladder, bladder carcinoma[44,45], normal esophagus, esophageal adenocarcinoma[41,46], normal brain, glioblastoma multiform[34,36], normal oral mucosa, head and neck carcinoma[47,48], normal B cell, lymphoma[49,50], normal pancreas, pancreatic adenocarcinoma[51], normal testis and adult male germ cell tumor[43]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.

Figure 3

Association between APRIL expression and aggressiveness in various cancers. APRIL gene expression in glioma[52], bladder carcinoma[53], breast carcinoma[54,55] and cervical carcinoma[56]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.

Figure 4

TACI expression in various cancers. TACI gene expression in normal plasma cells, smoldering myeloma[60], normal thyroid, thyroid carcinoma[61] and lymphoma[62]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.