PURPOSE: This study investigated the prognostic importance of protein expression of ATP-binding cassette (ABC) transporters ABCC10 and ABCC11 in colorectal cancer. METHODS: Protein content of ABCC10 and ABCC11 was assessed in tumor tissue blocks of 140 colorectal cancer patients and associated with survival of patients with regard to 5-fluorouracil-based therapy. RESULTS: Low ABCC10 protein content in tumors increased hazard ratio of patient's death more than three times in comparison with high ABCC10-expressing tumors (P = 0.004). In contrast, the low ABCC11 content increased the hazard ratio of cancer recurrence in patients almost four times (P = 0.016). Analysis of patients treated with regimens based on 5-fluorouracil revealed that patients with low ABCC11 content in their tumors had shorter disease-free interval than those with higher content (P = 0.024). CONCLUSIONS: The present study shows for the first time that the protein expression of ABCC10 significantly associates with overall survival and the expression of ABCC11 with disease-free interval of colorectal cancer patients and provides strong impulse for further validation of their prognostic value in colorectal cancer.
- MeSH
- ATP-Binding Cassette Transporters metabolism MeSH
- Antimetabolites, Antineoplastic therapeutic use MeSH
- Fluorouracil therapeutic use MeSH
- Colorectal Neoplasms drug therapy pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Survival Rate MeSH
- Follow-Up Studies MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- Multidrug Resistance-Associated Proteins metabolism MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Worldwide, colorectal cancer (CRC) is the third most common cancer, with the highest mortality rates occurring in Central Europe. The use of chemotherapy to treat CRC is limited by the inter-individual variability in drug response and the development of cancer cell resistance. ATP-binding cassette (ABC) transporters play a crucial role in the development of resistance by the efflux of anticancer agents outside of cancer cells. The aim of this study was to explore transcript levels of all human ABCs in tumours and non-neoplastic control tissues from CRC patients collected before the first line of treatment by 5-fluorouracil (5-FU)-containing regimen. The prognostic potential of ABCs was evaluated by the correlation of transcript levels with clinical factors. Relations between transcript levels of ABCs in tumours and chemotherapy efficacy were also addressed. The transcript profile of all known human ABCs was assessed using real-time polymerase chain reaction with a relative standard curve. The majority of the studied ABCs were down-regulated or unchanged between tumours and control tissues. ABCA12, ABCA13, ABCB6, ABCC1, ABCC2 and ABCE1 were up-regulated in tumours versus control tissues. Transcript levels of ABCA12, ABCC7 and ABCC8 increased in direction from colon to rectum. Additionally, transcript levels of ABCB9, ABCB11, ABCG5 and ABCG8 followed the reverse significant trend, i.e. a decrease in direction from colon to rectum. The transcript level of ABCC10 in tumours correlated with the grade (P = 0.01). Transcript levels of ABCC6, ABCC11, ABCF1 and ABCF2 were significantly lower in non-responders to palliative chemotherapy in comparison with responders. The disease-free interval of patients treated by adjuvant chemotherapy was significantly shorter in patients with low transcript levels of ABCA7, ABCA13, ABCB4, ABCC11 and ABCD4. In conclusion, ABCC11 may be a promising candidate marker for a validation study on 5-FU therapy outcome.
- MeSH
- ATP-Binding Cassette Transporters genetics MeSH
- Chemotherapy, Adjuvant MeSH
- Antineoplastic Agents therapeutic use MeSH
- Colon metabolism MeSH
- Colorectal Neoplasms drug therapy genetics mortality MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger genetics MeSH
- Neoplasm Metastasis MeSH
- Survival Rate MeSH
- Pilot Projects MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Prognosis MeSH
- Disease Progression MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Rectum metabolism MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
