Expression of tumor-driving pathways and genes in adenoid cystic carcinoma of the parotid gland

Introduction:

Adenoid cystic carcinoma (ACC) is a rare but highly malignant tumor of the parotid gland, which shows a poor long-term prognosis. In particular, the perineural invasion leads to locoregional recurrences or lung metastases after years. The underlying molecular mechanisms remain largely unknown. Knowledge about the tumor-driving signaling pathways could be used to identify targets of diagnostics and treatment.

Methods:

From 14 patients with ACC and the corresponding non-tumor area, formalin fixed and paraffin embedded tissue materials were used for microdissection followed by total RNA isolation. By using the "PanCancer Pathway" of the NanoString's nCounter technology, the gene expression of 770 genes were analyzed.

Results:

Expression profiling and subsequent hierarchical cluster analysis clearly differentiated between non-tumor gland tissue samples and ACC. The majority of ACC show an upregulation of chromatin modification, cell cycle apoptosis, DNA damage repair, as well as NOTCH, TGFbeta, and WNT signaling. In contrast transcriptional misregulation as well as PI3K, MAPK, RAS, HEDGEHOG and JAK-STAT signaling was down-regulated. In particular, the NOTCH pathway could be a potential target for future ACC treatment strategies. Moreover, FANCA, which is involved in DNA repair is significantly upregulated (Fc> 2, pBH = 0.002) in ACC vs. non-tumor. Importantly, the prognostic potential (Disease Free Survival) of FANCA expression in ACC was demonstrated (p < 0.05).

Conclusions:

The genetic profile in ACC, analyzed by the NanoString Technology can help to better understand tumor biology. Furthermore, this could lead to important insights necessary to develop optimized therapeutically solutions.

Publication History

Publication Date:
23 April 2019 (online)