Table 2.
Gene/protein expression or metabolic enzyme activity in colorectal cancer cells and correlation with outcome of patients receiving fluoropyrimidine-based chemotherapy
| Treatment setting | Method | Patients (n) | Better response to chemotherapy | Form of the disease | Ref. |
| Thymidylate synthase (TYMS) [OMIM # 188350] | |||||
| 5-FU | RT-PCR | 29 | Low expression | mCRC | Iyevleva et al[24] |
| 5-FU | RT-PCR | 39 | Low expression | CRC | Ishida et al[25] |
| 5-FU | IHC | 57 | Low expression | mCRC | Hosokawa et al[26] |
| 5-FU | IHC | 62 | Low expression | aCRC | Ciaparrone et al[27] |
| 5-FU | RT-PCR | 92 | Low expression | CRC | Nakajima et al[28] |
| 5-FU | RT-PCR | 309 | Low expression | CRC | Kornmann et al[29] |
| 5-FU | IHC | 391 | Not significant | aCRC | Westra et al[438] |
| 5-FU | IHC | 945 | Not significant | CRC | Soong et al[107] |
| FUdR | IHC | 36 | Low expression | mCRC | Davies et al[31] |
| 5-FU/LV or 5-FU | RT-PCR | 29 | Low expression | mCRC | Kornmann et al[32] |
| 5-FU/LV | RT-PCR | 33 | Low expression | aCRC | Salonga et al[17] |
| 5-FU/LV | RT-PCR | 36 | Low expression | mCRC | Lenz et al[7] |
| 5-FU/LV | RT-PCR | 42 | Low expression | CRC | Leichman et al[19] |
| 5-FU/LV | RIA | 102 | Low expression | mCRC | Etienne et al[33] |
| 5-FU/OX | RT-PCR | 45 | Low expression | aCRC | Shirota et al[34] |
| 5-FU/MTX | IHC | 108 | Low expression | aCRC | Paradiso et al[35] |
| 5-FU or 5-FU/MTX or 5-FU/LV | IHC | 24 | Not significant | aCRC | Belvedere et al[439] |
| 5-FU or 5-FU/MTX or 5-FU/LV | IHC | 27 | Not significant | mCRC | Aschele et al[23] |
| 5-FU or 5-FU/MTX or 5-FU/LV | IHC | 48 | Low expression | mCRC | Aschele et al[36] |
| 5-FU/LV/CPT-11 | RT-PCR | 13 | Low expression | aCRC | Yanagisawa et al[37] |
| 5-FU/LV/CPT-11 | IHC | 54 | Low expression | aCRC | Bendardaf et al[38] |
| 5-FU/LV/CPT-11 | IHC | 57 | Not significant | aCRC | Paradiso et al[440] |
| UFT/LV | RT-PCR | 37 | Low expression | mCRC | Ichikawa et al[39] |
| Capecitabine | RT-PCR | 37 | Not significant | aCRC | Vallböhmer et al[97] |
| Capecitabine | IHC | 39 | Not significant | CRC | Lindebjerg et al[441] |
| Capecitabine/CPT-11 | IHC | 556 | Not significant | aCRC | Koopman et al[110] |
| 5-FU-based therapy | IHC | 681 | Not significant | CRC | Karlberg et al[442] |
| Dihydropyrimidine dehydrogenase (DPYD) (OMIM # 612779) | |||||
| 5-FU | RT-PCR | 29 | Not significant | mCRC | Iyevleva et al[24] |
| 5-FU | RT-PCR | 39 | Not significant | CRC | Ishida et al[25] |
| 5-FU | IHC | 62 | Low expression | aCRC | Ciaparrone et al[27] |
| 5-FU | IHC | 303 | Low expression | CRC | Jensen et al[443] |
| 5-FU | RT-PCR | 309 | Low expression | CRC | Kornmann et al[29] |
| 5-FU | IHC | 391 | Not significant | aCRC | Westra et al[438] |
| 5-FU | IHC | 945 | Not significant | CRC | Soong et al[107] |
| 5-FU/LV | RT-PCR | 33 | Low expression | aCRC | Salonga et al[17] |
| UFT/LV | RT-PCR | 37 | Low expression | mCRC | Ichikawa et al[39] |
| 5-FU/LV/CPT-11 | RT-PCR | 13 | Not significant | aCRC | Yanagisawa et al[37] |
| Capecitabine | RT-PCR | 37 | Low expression | aCRC | Vallböhmer et al[97] |
| Capecitabine/CPT-11 | RT-PCR | 67 | Not significant | aCRC | Meropol et al[98] |
| Capecitabine/CPT-11 | IHC | 556 | Low expression | aCRC | Koopman et al[110] |
| 5-FU-based therapy | ELISA | 64 | Low expression | aCRC | Oi et al[444] |
| 5-FU-based therapy | RT-PCR | 102 | Low expression | CRC | Lassman et al[445] |
| 5-FU-based therapy | RT-PCR | 144 | Low expression | aCRC | Gustavsson et al[446] |
| 5-FU-based therapy | IHC | 150 | Low expression | aCRC | Tokunaga et al[447] |
| Thymidine phosphorylase (TYMP) (OMIM # 131222) | |||||
| 5-FU | IHC | 62 | Not significant | aCRC | Ciaparrone et al[27] |
| 5-FU | IHC | 945 | Not significant | CRC | Soong et al[107] |
| 5-FU/LV | RT-PCR | 33 | Low expression | aCRC | Salonga et al[17] |
| 5-FU/LV/CPT-11 | RT-PCR | 13 | Not significant | aCRC | Yanagisawa et al[37] |
| Capecitabine | RT-PCR | 37 | Not significant | aCRC | Vallböhmer et al[97] |
| Capecitabine/OX | IHC | 41 | High expression | mCRC | Petrioli et al[448] |
| Capecitabine/CPT-11 | RT-PCR | 67 | High expression | aCRC | Meropol et al[98] |
| Capecitabine/CPT-11 | IHC | 556 | Not significant | aCRC | Koopman et al[110] |
| 5-FU-based therapy | RT-PCR | 144 | Low expression | aCRC | Gustavsson et al[446] |
| 5-FU-based therapy | IHC | 150 | Low expression | aCRC | Tokunaga et al[447] |
| Uridine monophosphate synthetase (UMPS) (OMIM #613891) | |||||
| 5-FU | RT-PCR | 38 | Not significant | mCRC | Sameshima et al[449] |
| 5-FU | RT-PCR | 39 | Not significant | CRC | Ishida et al[25] |
| 5-FU/LV/OX | RT-PCR | 58 | Not significant | CRC | Dong et al[450] |
| 5-FU/LV/cisplatin | RT-PCR | 22 | High expression | mCRC | Matsuyama et al[113] |
| UFT | RIA | 40 | High expression | CRC | Ichikawa et al[114] |
| UFT | RIA | 124 | High expression | CRC | Ochiai et al[115] |
| UFT | IHC | 150 | High expression | CRC | Tokunaga et al[116] |
| UFT | IHC | 160 | High expression | CRC | Tokunaga et al[117] |
| UFT/LV | RT-PCR | 37 | High expression | mCRC | Ichikawa et al[118] |
| UFT/LV | RT-PCR | 103 | High expression | CRC | Yamada et al[119] |
| 5-FU-based therapy | RT-PCR | 10 | Not significant | CRC | Ishibashi et al[451] |
| 5-FU-based therapy | RIA | 11 | Not significant | CRC | Yamada et al[452] |
| 5-FU-based therapy | RT-PCR | 52 | Not significant | CRC | Kinoshita et al[453] |
| 5-FU-based therapy | RIA | 54 | High expression | CRC | Fujii et al[120] |
| 5-FU-based therapy | RIA | 90 | High expression | CRC | Ochiai et al[121] |
5-FU: 5-fluorouracil; LV: Leucovorin; FUdR: 5-fluorodeoxyuridine; MTX: Methotrexate; OX: Oxaliplatin; UFT: Compound tegafur tablets; CPT-11: Irinotecan; CTX: Cetuximab; RT-PCR: Reverse trascriptase polymerase chain reaction; IHC: Immunohistochemistry; ELISA: Enzyme-linked immunosorbent ssay; RIA: Radioimmunoassay; CRC: Colorectal cancer; aCRC: Advanced colorectal cancer; mCRC: Metastatic colorectal cancer.