Prognostic implication of ABC transporters and cancer stem cell markers in patients with stage III colon cancer receiving adjuvant FOLFOX‑4 chemotherapy

Abstract

Cancer stem cell (CSC) and ATP-binding cassette (ABC) transporters are associated with treatment resistance and outcomes of patients with cancer. The present study investigated the prognostic implications of pre-therapeutic expression of ABC transporters and CSC markers in patients with colon cancer (CC) who received adjuvant 5-fluorouracil, leucovorin and oxaliplatin combination therapy (FOLFOX-4). The immunohistochemical expression of 3 ABC transporters, including ABC subfamily C member 2 (ABCC2), ABCC3 and ABC subfamily G member 2 (ABCG2), and 3 CSC markers, including sex determining region Y-box 2 (SOX2), leucine-rich repeat-containing G protein-coupled receptor 5 and aldehyde dehydrogenase 1, were determined in 164 CC tissues from patients with stage III CC, who underwent postoperative FOLFOX-4 chemotherapy. The association between the protein expression and patients' prognoses was statistically analyzed. ABCG2 was associated with favorable overall survival rate (OS; P=0.001), and ABCC2, ABCG2 and SOX2 were associated with increased disease-free survival rate (DFS; P=0.001, 0.002 and 0.013, respectively). In multivariate analyses, ABCG2 was an independent prognostic factor for OS [hazard ratio (HR)=2.877; P=0.046], and ABCC2 and SOX2 were independent prognostic factors for DFS (HR=2.831; P=0.014; HR=2.558, P=0.020, respectively). ABCC2, ABCG2 and SOX2 may be promising prognostic markers for patients with CC receiving FOLFOX-4 therapy.

Clinical and Survival Impact of Sex-Determining Region Y-Box 2 in Colorectal Cancer: An Integrated Analysis of the Immunohistochemical Study and Bioinformatics Analysis

“…For example, in the future, the expression of SOX2 is defined as positive or negative, which should be recommended using a uniform standard. Fourth, only Han et al reported that SOX2 expression was correlated with DFS in 164 CRC cases (HR � 2.558, P � 0.020) [6]. Finally, sample sizes on the analyses between SOX2 expression and the clinicopathological features and the prognosis were relatively small in the meta-analysis, more studies with large study population are necessary to further determine whether SOX2 is correlated with clinical and prognostic value in CRC based on IHC methods.…”

“…SOX2 expression is correlated with the prognosis of some human cancers such as non-small cell lung cancer and cervical cancer with better prognosis [20,21] and breast cancer and gastric cancer with worse prognosis [18,19]. Studies have reported that SOX2 is frequently expression in CRC [6,34,35]. However, the function of SOX2 and its survival impact in patients with CRC are still largely uncertain.…”

“…Based on the selection criteria, inappropriate studies were excluded. Finally, 13 studies published between 2010 and 2019 were identified in the present meta-analysis [6,14,23,24,[34][35][36][37][38][39][40][41][42], including 2337 patients with CRC. Eligible studies were conducted in China, Korea, Singapore, Australia, Germany, Sweden, and e Netherlands.…”

“…10 studies with 1431 cases evaluated the relationship between SOX2 expression and the clinicopathological parameters [14,23,24,[35][36][37][38][39][40][41]. Five studies Journal of Oncology with 1451 cases assessed the association between SOX2 expression and the prognosis using multivariate Cox survival analysis [6,23,24,34,42]. 13 studies were considered to be of high quality by using NOS.…”

“…Cancer stem cells (CSCs) are a special subpopulation of tumor cells and have the ability and characteristics of self-renewal and multilineage differentiation and proliferation potential, which are related to tumor progression, metastasis, recurrence, prognosis, and drug resistance [6][7][8]. Many CSC-related markers have been identified and reported to be associated with poor prognosis and resistance to therapy in cancer [9,10].…”