Downregulation of ATP-Binding Cassette Subfamily C Member 4 Increases Sensitivity to Neoadjuvant Radiotherapy for Locally Advanced Rectal Carcinoma

Abstract

Our data indicate that ATP-binding cassette subfamily C member 4 may be a useful molecular marker in predicting radiosensitivity, and a potential target in improving the response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients.

Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

“…48 Multidrug resistance-associated proteins (MRPs), also known as adenosine triphosphate-binding cassette (ABC) transporters, are another important class of molecules that might be associated with response to irradiation and cytotoxic drugs. 49 The significant association observed between sensitivity to neoadjuvant RT and downregulation of ABCC4 (MRP4) indicates a possible role of this protein as a predictive biomarker, 50 and the correlation between high ABCC4 expression and shorter DFS makes it a good biomarker of poor outcome in LARC. 51 Finally, the negative effect on pathological response of aberrant expression of MRP3, another member of this family, was recently shown by Yu et al in 144 pretreatment rectal biopsies from patients treated with NCRT.…”

Prognostic Significance and Molecular Mechanism of ATP-Binding Cassette Subfamily C Member 4 in Resistance to Neoadjuvant Radiotherapy of Locally Advanced Rectal Carcinoma

“…According to our previous data, the positive rate of ABCC4 expression in pretreatment tissue specimens of LARC was substantial while ABCC4 expression in biopsy specimens was significantly associated with short-term pathological response to nRT in LARC patients [5]. In the present study, we aimed to evaluate the long-term prognostic significance of ABCC4 in this group of LARC patients treated with nRT.…”

“…Biopsy tissue specimens were obtained from 121 LARC patients with a mean age of 57.8 (SD = 11.2) years, as previously described [5]. Pretreatment biopsy was examined to confirm the diagnosis of rectal adenocarcinoma.…”

“…Our previous studies have demonstrated a combined predictive value of p53 and p21 for tumor regression after preoperative nRT in rectal carcinoma patients and identified that ATP-binding cassette subfamily C member 4 (ABCC4) may play a role in response to irradiation of CRC cell line HT29 in vitro [4]–[5]. ABCC4 has been identified as an active ATP-dependent export pump belonging to the ATP-binding cassette transporter superfamily for exporting cyclic nucleotides and organic anions across extra- and intra-cellular membranes [6].…”

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

“…Cells were harvested at 24 h after being treated with irradiation of 4 Gy for cell apoptosis analysis by flow cytometry assay as described previously [16].…”