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Table 3 Functional studies of candidate genes

From: Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines

Gene symbol Selection strategy Cytotoxicity validation in cancer cell lines
SNP vs. IC50 Integrated analysis Both SU86 and MDA231 Either THP-1 or BDCM
SNP Location P < 10-4 SNP vs. Exp P < 10-4 (cancer cell lines) (leukemia cell lines)
Exp vs. IC50 P <10-4
PIGB Intron/coding/5UTR/3UTR Gem Gem Yes NP
C3orf23 5UTR/upstream Gem Gem No NP
ZADH2    Gem Yes NP
ARHGEF12    Gem No NP
DPP7    Gem No NP
PSME3    Gem Yes NP
NIPSNAP3B Intron/5UTR Gem   No NP
PIK3R1 Flanking_5UTR/3UTR Gem   No NP
DOK6 Intron Gem   Yes NP
TGFBI Flanking_5UTR Gem   Yes NP
UNC13C    AraC No No
C14orf169    AraC Yes NP
MAP4K4    AraC No NP
URB2 Downstream AraC   No No
TUSC3 Intron/5UTR/3UTR AraC   Yes No
LARS2 5UTR AraC   Yes No
RIS1 (TMEM158) 5UTR AraC   Yes Yes
IGSF4 (CADM1) Intron/downstream/3UTR AraC   No No
LNX2 Intron/5UTR/3UTR AraC   Yes No
SMC2 3UTR AraC   Yes Yes
PLD5 Intron Both   No NP
GPR98 Intron Both   No No
HLA-DRA Intron/3UTR Both   Yes No
ZNF215 Flanking_5UTR/3UTR/coding Both   No No
CABLES1    Both No No
  1. The table lists the top 26 candidate genes selected for siRNA screening for both gemcitabine and AraC, with MTS assay results as well as QRT-PCR assay results when appropriate.
  2. A total of 26 genes were selected for siRNA screening, with 11 genes for gemcitabine, 10 for AraC, and 5 for both. For the validation assays with MTS and QRT-PCR, “Yes” indicates that knockdown of the gene altered drug cytotoxicity, while “No” indicates no alteration. “NP” indicates not performed. The genes that are bolded were functionally validated.