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This study investigated the potential of single nucleotide polymorphisms as predictors of survival in two cohorts comprising 417 metastatic colorectal cancer (mCRC) patients treated with the FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) regimen. The rs4806668G > T of the ribosomal protein gene  RPL28  was associated with shorter progression-free survival and overall survival by 5 and 9 months ( P  = 0.002), with hazard ratios of 3.36 ( P  < 0.001) and 3.07 ( P  = 0.002), respectively. The rs4806668T allele was associated with an increased  RPL28  expression in transverse normal colon tissues (n = 246,  P  = 0.007).  RPL28  expression was higher in colorectal tumors compared to paired normal tissues by up to 124% ( P  < 0.001) in three independent datasets. Metastatic cases with highest  RPL28  tumor expression had a reduced survival in two datasets (n = 88,  P  = 0.009 and n = 56,  P  = 0.009). High  RPL28  was further associated with changes in immunoglobulin and extracellular matrix pathways. Repression of RPL28 reduced proliferation by 1.4-fold to 5.6-fold ( P  < 0.05) in colon cancer HCT116 and HT-29 cells. Our findings suggest that the ribosomal RPL28 protein may influence mCRC outcome.

Germline variability and tumor expression level of ribosomal protein gene RPL28 are associated with survival of metastatic colorectal cancer patients