Drug transporters such as
P-glycoprotein (ABCB1) have been associated with
chemotherapy resistance and are considered unfavorable prognostic factors for survival of
cancer patients. Analyzing
mRNA expression levels of a subset of
drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or
protein expression by tissue microarray (TMA) in
tumor samples of
therapy naïve stage IV
head and neck squamous cell carcinoma (
HNSCC) (qRT-PCR, n = 40; TMA, n = 61), this in situ study re-examined the significance of transporter expression for progression-free survival (PFS) and overall survival (OS). Data from The
Cancer Genome Atlas database was used to externally validate the respective findings (n = 317). In general,
HNSCC tended to lower expression of
drug transporters compared to normal epithelium. High ABCB1
mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357) and overall survival (OS, p = 0.0535). Similar results were obtained for the
mRNA of ABCC1 (
MRP1,
multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038). In contrast,
protein expression of ATP7b (
copper transporter ATP7b),
mRNA expression of ABCG2 (BCRP,
breast cancer resistance
protein), ABCC2 (MRP2), and SLC31A1 (hCTR1, human
copper transporter 1) did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of
HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of
drug efflux transporters indicates poor survival, but demonstrates that expression of single
drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of
drug transporters on survival of patients with
HNSCC.