Electronic Supplementary Material s87

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Electronic Supplementary Material

Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer

Journal of Cancer Research and Clinical Oncology

Seon Ae Roh1,2,3 ∙ In Ja Park1,2 ∙ Yong Sik Yoon1,2,3 ∙ Yi Hong Kwon1,3 ∙ Jin Hwa Chung1 ∙ Tae Won Kim1,4 ∙ Dong Hyung Cho5 ∙ Byung Ho Lim6 ∙ Seon Kyu Kim6 ∙ Seon Young Kim6 ∙ Yong Sung Kim6 ∙ Jin Cheon Kim1,2,3

1Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea

2Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

3Institute of Innovative Cancer Research, Asan Medical Center, Seoul, Korea

4Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

5Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, Korea

6Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea

Correspondence:

Jin Cheon Kim, MD, PhD, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Tel: 822-3010-3489; Fax: 822-474-9027; E-mail:

Yong Sung Kim, PhD, Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea. Tel: 042-879-8124; Fax: 82-42-879-8119; E-mail:

Table S1

Demographic, clinical features and tumor responses of patients treated with bevacizumab regimens.

Demographic and clinical features
Gender, male/female (%) / 53 (45.7) / 63 (53.8)
Age, mean (range) / 54 (27–84)
ECOG performance status, 0/1/2 / 4 (3.4) / 95 (81.2) / 10 (8.5) /8 (6.9)
Curative tumor resection / 42 (36.3)
Location of primary tumor, colon/rectum / 82 (70.7) / 34 (29.1)
No. of prior chemotherapy lines, 0/1/2≥3 / 36 (31.0) / 29 (24.8) / 23 (19.7) / 22 (19.0) /6 (5.2)
Prior target agent use / 22 (18.8)
No. of metastatic sites, 1/2≥3 / 59 (50.9) / 37 (31.6) / 20 (17.1)
Tumor responses
CR
PR
SD
PD / 9 (7.8)
35 (29.9)
48 (41)
23 (19.7)
Survival period, mean±SEM, months
PFS (range), months / 11.2 ± 10 (1–59)
OS (range), months / 21.5 ± 20.1 (1–115)

ECOG Eastern Cooperative Oncology Group, CR complete response, PR partial response, SD stable disease, PD progressive disease, PFS progression-free survival, OS overall survival, No. number

Table S2. One-hundred-and-seven single nucleotide variants significantly associated with FRB-driven tumor inhibition rates.

Chromosome / Position / Association P (exome sequencing)
chr16 / 70975401 / 2.42E-05
chr3 / 154890037 / 2.42E-05
chr17 / 7951149 / 6.42E-05
chr17 / 7951878 / 6.42E-05
chr5 / 177612734 / 6.42E-05
chr14 / 105418264 / 6.42E-05
chr14 / 105416872 / 8.53E-05
chr14 / 105416087 / 8.53E-05
chr14 / 105416784 / 0.000146
chr14 / 21874068 / 0.0001545
chr14 / 105458512 / 0.0001601
chr14 / 105458521 / 0.0001601
chr14 / 105461067 / 0.0001601
chr1 / 11980449 / 0.0002116
chr6 / 46806939 / 0.0002116
chr7 / 76871113 / 0.0002116
chr13 / 23507710 / 0.0002297
chr2 / 96595271 / 0.0002534
chr6 / 13949673 / 0.0002603
chr20 / 20033319 / 0.0002714
chr15 / 57555523 / 0.0002887
chr1 / 31898463 / 0.0003043
chr1 / 36935128 / 0.0003043
chr1 / 203149120 / 0.0003043
chr1 / 206579683 / 0.0003043
chr10 / 18270208 / 0.0003043
chr10 / 18276586 / 0.0003043
chr11 / 38133302 / 0.0003043
chr14 / 19491760 / 0.0003043
chr15 / 53901720 / 0.0003043
chr15 / 76175828 / 0.0003043
chr19 / 51874965 / 0.0003043
chr2 / 62112081 / 0.0003043
chr2 / 150426399 / 0.0003043
chr22 / 38483247 / 0.0003043
chr3 / 138025136 / 0.0003043
chr8 / 54745538 / 0.0003043
chr15 / 101445815 / 0.0003043
chr1 / 36937065 / 0.0003043
chr10 / 115481018 / 0.0003106
chr1 / 6591937 / 0.0003122
chr14 / 50641347 / 0.0003137
chr7 / 618855 / 0.0003175
chr7 / 618869 / 0.0003175
chr7 / 618938 / 0.0003175
chr12 / 123001737 / 0.0003262
chr12 / 123003317 / 0.0003262
chr13 / 95410745 / 0.0003383
chr14 / 105416823 / 0.0003444
chr14 / 105416010 / 0.0003467
chr1 / 100330237 / 0.0003482
chr2 / 192247808 / 0.000353
chr23 / 69250308 / 0.0003794
chr10 / 135439049 / 0.0003869
chr9 / 72338180 / 0.0003949
chr8 / 145623963 / 0.000401
chr19 / 49368843 / 0.000401
chr19 / 49377242 / 0.000401
chr19 / 49377319 / 0.000401
chr19 / 49377436 / 0.000401
chr22 / 21837429 / 0.0004335
chr1 / 3645835 / 0.000447
chr20 / 29628112 / 0.0004792
chr3 / 39172167 / 0.000487
chr17 / 7948425 / 0.000546
chr15 / 89151262 / 0.0005484
chr5 / 180375095 / 0.00056
chr7 / 142457541 / 0.0005662
chr7 / 154897972 / 0.000586
chr11 / 125891269 / 0.0006027
chr1 / 3785172 / 0.0006219
chr19 / 41448205 / 0.0006361
chr10 / 17110595 / 0.000646
chr16 / 22588118 / 0.0006702
chr4 / 63684558 / 0.0007059
chr18 / 21119777 / 0.0007068
chr23 / 148062377 / 0.0007218
chr3 / 97983040 / 0.0007238
chr1 / 232650750 / 0.0007583
chr12 / 94972290 / 0.0007601
chr10 / 81374977 / 0.0007668
chr3 / 124732618 / 0.0007724
chr14 / 105417147 / 0.0007913
chr2 / 166799596 / 0.0007964
chr7 / 143029371 / 0.0008103
chr22 / 20398374 / 0.0008228
chr1 / 203151794 / 0.0008234
chr17 / 10614442 / 0.0008237
chr1 / 119988404 / 0.0008245
chr4 / 103747541 / 0.0008263
chr4 / 103789782 / 0.0008263
chr4 / 103883608 / 0.0008263
chr1 / 6190215 / 0.0008338
chr14 / 105458555 / 0.0008662
chr19 / 9028432 / 0.0008726
chr3 / 111637816 / 0.0008768
chr1 / 100329889 / 0.000898
chr15 / 38792430 / 0.0009136
chr3 / 9488715 / 0.0009136
chr8 / 30841331 / 0.0009136
chr8 / 30854033 / 0.0009136
chr17 / 22258620 / 0.0009287
chr5 / 169129284 / 0.0009395
chr6 / 117678083 / 0.0009416
chr13 / 103301130 / 0.0009439
chr1 / 171511039 / 0.0009576
chr9 / 110893030 / 0.0009972

Table S3

Single nucleotide variants exhibiting a correlation coefficient (r) between variant-allele frequencies in RNA-seq data and FRB-driven tumor inhibition rates greater than 0.5.

Chromosome / Position / Genes / Correlation
(RNA-seq)
chr19 / 49368843 / PLEKHA4 / 0.77
chr19 / 54726324 / LILRB3 / 0.76
chr15 / 101445815 / ALDH1A3 / 0.76
chr3 / 9426224 / THUMPD3 / 0.76
chr19 / 49377242 / PPP1R15A / 0.74
chr8 / 145603114 / ADCK5 / 0.74
chr19 / 49377319 / PPP1R15A / 0.74
chr19 / 49377436 / PPP1R15A / 0.74
chr3 / 9425944 / THUMPD3 / 0.72
chr20 / 23028724 / THBD / 0.72
chr1 / 228564884 / OBSCN / 0.71
chr15 / 52643564 / MYO5A / 0.69
chr9 / 98211572 / PTCH1 / 0.68
chr11 / 126162468 / TIRAP / 0.68
chr12 / 122186317 / TMEM120B / 0.67
chr1 / 52264064 / NRD1 / 0.67
chr12 / 107219572 / RIC8B / 0.67
chr4 / 57250285 / AASDH / 0.67
chr15 / 75499995 / C15orf39 / 0.66
chr19 / 49376582 / PPP1R15A / 0.66
chr12 / 10313448 / OLR1 / 0.66
chr5 / 147286054 / C5orf46 / 0.64
chr19 / 54745550 / LILRA6 / 0.64
chr6 / 46684222 / PLA2G7 / 0.64
chr21 / 34926043 / SON / 0.64
chr1 / 89528860 / GBP1 / 0.64
chr22 / 36556823 / APOL3 / 0.64
chr1 / 25679393 / TMEM50A / 0.64
chr15 / 81234287 / KIAA1199 / 0.64
chr3 / 39139776 / GORASP1 / 0.64
chr11 / 644568 / DEAF1 / 0.64
chr6 / 135754208 / AHI1 / 0.63
chr5 / 94230358 / MCTP1 / 0.63
chr11 / 47380340 / SPI1 / 0.63
chr19 / 54726347 / LILRB3 / 0.63
chr16 / 88504868 / ZNF469 / 0.63
chr4 / 30725987 / PCDH7 / 0.63
chr19 / 48737706 / CARD8 / 0.63
chr5 / 43295881 / HMGCS1 / 0.63
chr9 / 135277341 / TTF1 / 0.62
chr19 / 49377086 / PPP1R15A / 0.62
chr1 / 31347399 / SDC3 / 0.62
chr19 / 54746081 / LILRB3;LILRA6;LILRA6;LILRA6;LILRA6;LILRA / 0.61
chr14 / 51224417 / NIN / 0.61
chr1 / 52266350 / NRD1 / 0.61
chr22 / 50878196 / PPP6R2 / 0.61
chr12 / 108954823 / SART3 / 0.60
chr6 / 126278230 / HINT3 / 0.60
chr17 / 46939658 / CALCOCO2 / 0.60
chr11 / 77921527 / USP35 / 0.60
chr12 / 57039080 / ATP5B / 0.60
chr15 / 43622265 / LCMT2 / 0.60
chr4 / 57221348 / AASDH / 0.60
chr19 / 54745989 / LILRB3;LILRA6;LILRA6;LILRA6;LILRA6;LILRA / 0.59
chr1 / 146215138 / WI2-3658N16.1 / 0.59
chr14 / 88401213 / GALC / 0.59
chr3 / 197427557 / KIAA0226 / 0.59
chr17 / 17409560 / PEMT / 0.59
chr15 / 42115747 / MAPKBP1 / 0.59
chr13 / 21562948 / LATS2 / 0.59
chr14 / 102815042 / CINP / 0.58
chr1 / 161599693 / FCGR3B / 0.58
chr20 / 49446886 / BCAS4 / 0.58
chr11 / 67258391 / AIP / 0.58
chr2 / 85595818 / ELMOD3 / 0.57
chr21 / 34945721 / SON / 0.57
chr11 / 48146622 / PTPRJ / 0.57
chr12 / 7090193 / LPCAT3 / 0.57
chr22 / 41601385 / L3MBTL2 / 0.57
chr9 / 101765841 / COL15A1 / 0.57
chr4 / 148944467 / ARHGAP10 / 0.57
chr2 / 88876094 / EIF2AK3 / 0.57
chr19 / 51728641 / CD33 / 0.57
chr21 / 30331935 / LTN1 / 0.57
chr2 / 112552427 / ANAPC1 / 0.57
chr11 / 48145375 / PTPRJ / 0.56
chr19 / 50412217 / NUP62 / 0.56
chr18 / 2547500 / METTL4 / 0.56
chr7 / 158590740 / ESYT2 / 0.56
chr2 / 202252539 / TRAK2 / 0.56
chr19 / 41111069 / LTBP4 / 0.56
chr1 / 154573967 / ADAR / 0.56
chr14 / 105415469 / AHNAK2 / 0.56
chr14 / 105415608 / AHNAK2 / 0.56
chr14 / 105407798 / AHNAK2 / 0.56
chr14 / 105408182 / AHNAK2 / 0.56
chr19 / 8669931 / ADAMTS10 / 0.56
chr14 / 105410183 / AHNAK2 / 0.56
chr14 / 105411781 / AHNAK2 / 0.56
chr14 / 105413204 / AHNAK2 / 0.56
chr14 / 105412259 / AHNAK2 / 0.56
chr19 / 14862430 / EMR2 / 0.56
chr3 / 197403844 / KIAA0226 / 0.56
chr5 / 75991420 / IQGAP2 / 0.56
chr15 / 50878630 / TRPM7 / 0.55
chr6 / 143823112 / FUCA2 / 0.55
chr10 / 105209292 / CALHM2 / 0.55
chr4 / 961373 / DGKQ / 0.55
chr20 / 36841914 / KIAA1755 / 0.55
chr1 / 17083888 / MST1P9 / 0.55
chr3 / 32280542 / CMTM8 / 0.55
chr7 / 618938 / PRKAR1B / 0.55
chr5 / 176930135 / DOK3 / 0.54
chr3 / 124731689 / HEG1 / 0.54
chr14 / 105406238 / AHNAK2 / 0.54
chr20 / 3204031 / ITPA / 0.54
chr8 / 120429024 / NOV / 0.54
chr21 / 30339234 / LTN1 / 0.54
chr3 / 112063850 / CD200 / 0.54
chr10 / 46242094 / FAM21C / 0.54
chr11 / 62298597 / AHNAK / 0.54
chr2 / 44004010 / DYNC2LI1 / 0.54
chr19 / 41117869 / LTBP4 / 0.53
chr7 / 4823392 / KIAA0415 / 0.53
chr10 / 98469507 / PIK3AP1 / 0.53
chr12 / 106460938 / NUAK1 / 0.53
chr1 / 236719193 / HEATR1 / 0.53
chr10 / 99376152 / MORN4 / 0.53
chr15 / 34820441 / GOLGA8B / 0.53
chr6 / 56394926 / DST / 0.53
chr14 / 105416230 / AHNAK2 / 0.53
chr5 / 140564048 / PCDHB16 / 0.53
chr17 / 34582971 / TBC1D3C / 0.53
chr14 / 105417894 / AHNAK2 / 0.53
chr11 / 73988167 / P4HA3 / 0.53
chr19 / 58386508 / ZNF814 / 0.53
chr12 / 42853871 / PRICKLE1 / 0.53
chr7 / 111487098 / DOCK4 / 0.53
chr14 / 105412066 / AHNAK2 / 0.53
chr3 / 178968634 / KCNMB3 / 0.53
chr12 / 122079295 / ORAI1 / 0.53
chr15 / 99666979 / SYNM / 0.53
chr12 / 12483764 / MANSC1 / 0.53
chr6 / 74521947 / CD109 / 0.53
chr20 / 36845738 / KIAA1755 / 0.53
chr3 / 46399208 / CCR2 / 0.53
chr15 / 57839587 / CGNL1 / 0.53
chr19 / 50463982 / SIGLEC11 / 0.53
chr14 / 105418344 / AHNAK2 / 0.53
chr14 / 105416959 / AHNAK2 / 0.53
chr14 / 105419234 / AHNAK2 / 0.53
chr15 / 34826284 / GOLGA8B / 0.53
chr3 / 137807259 / DZIP1L / 0.53
chr12 / 121600253 / P2RX7 / 0.53
chr1 / 48764419 / SPATA6 / 0.53
chr21 / 28305212 / ADAMTS5 / 0.53
chr14 / 55243178 / SAMD4A / 0.53
chr3 / 124732820 / HEG1 / 0.53
chr2 / 232597688 / PDE6D / 0.53
chr15 / 34168130 / AVEN / 0.53
chr1 / 156264648 / C1orf85 / 0.53
chr5 / 180276345 / ZFP62 / 0.53
chr8 / 121554051 / SNTB1 / 0.53
chr16 / 67242276 / LRRC29 / 0.53
chr20 / 34055194 / CEP250 / 0.53
chr16 / 16442408 / AC138969.4 / 0.53
chr1 / 153333264 / S100A9 / 0.53
chr1 / 1563702 / MIB2 / 0.53
chr8 / 48883929 / MCM4 / 0.53
chr18 / 5423515 / EPB41L3 / 0.53
chr8 / 145057916 / PARP10 / 0.53
chr19 / 5713245 / LONP1 / 0.53
chr11 / 213397 / RIC8A / 0.53
chr10 / 100003880 / C10orf28 / 0.53
chr12 / 3310411 / TSPAN9 / 0.53
chr1 / 232581501 / SIPA1L2 / 0.53
chr7 / 150739109 / ABCB8 / 0.53
chr5 / 54327231 / GZMK / 0.53
chr21 / 42767561 / MX2 / 0.53
chr5 / 54585118 / DHX29 / 0.53
chr6 / 159457244 / TAGAP / 0.53
chr9 / 139371041 / SEC16A / 0.53
chr17 / 40263349 / DHX58 / 0.53
chr9 / 114911572 / SUSD1 / 0.53
chr2 / 235951752 / SH3BP4 / 0.53
chr17 / 78298926 / RNF213 / 0.53
chr15 / 28436178 / HERC2 / 0.53
chr8 / 61655556 / CHD7 / 0.53
chr6 / 31324580 / HLA-B / 0.53
chr19 / 11226888 / LDLR / 0.53
chr8 / 146278473 / C8orf33 / 0.53
chr7 / 127222490 / GCC1 / 0.53
chr11 / 118918699 / HYOU1 / 0.53
chr11 / 62383988 / B3GAT3 / 0.53
chr9 / 136633707 / VAV2 / 0.53
chr3 / 98519494 / DCBLD2 / 0.53
chr5 / 176778287 / LMAN2 / 0.53
chr6 / 36936697 / MTCH1 / 0.53
chr19 / 871222 / MED16 / 0.53
chr2 / 64863311 / SERTAD2 / 0.53
chr22 / 37457585 / KCTD17 / 0.53
chr11 / 32122109 / RCN1 / 0.53
chr4 / 109084821 / LEF1 / 0.53
chr3 / 5244678 / EDEM1 / 0.53
chr12 / 9098149 / M6PR / 0.53
chr12 / 971262 / WNK1 / 0.53
chr5 / 149502735 / PDGFRB / 0.53
chr18 / 2772321 / SMCHD1 / 0.53
chr1 / 110464595 / CSF1 / 0.53
chr3 / 123512627 / MYLK / 0.53
chr16 / 75646262 / ADAT1 / 0.53
chr17 / 651144 / GEMIN4 / 0.53
chr3 / 180327501 / TTC14 / 0.53
chr10 / 45499009 / ZNF22 / 0.53
chr8 / 105503212 / LRP12 / 0.53
chr8 / 145745327 / LRRC14 / 0.53
chr14 / 24739664 / RABGGTA / 0.53
chr2 / 74654358 / RTKN / 0.53
chr5 / 168123398 / SLIT3 / 0.53
chr7 / 158664166 / WDR60 / 0.53
chr11 / 73611349 / PAAF1 / 0.53
chr6 / 152477230 / SYNE1 / 0.53
chr15 / 41223901 / DLL4 / 0.53
chr3 / 139097997 / COPB2 / 0.53
chr12 / 7091899 / LPCAT3 / 0.53