Scientific Publications Database

Article Title: Germline variability and tumor expression level of ribosomal protein gene RPL28 are associated with survival of metastatic colorectal cancer patients
Authors: Labriet, Adrien; Levesque, Eric; Cecchin, Erika; De Mattia, Elena; Villeneuve, Lyne; Rouleau, Michele; Jonker, Derek; Couture, Felix; Simonyan, David; Allain, Eric P.; Buonadonna, Angela; D'Andrea, Mario; Toffoli, Giuseppe; Guillemette, Chantal
Journal: SCIENTIFIC REPORTS Volume 9
Date of Publication:2019
Abstract:
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.