Predictive Value of Cancer Stem-Like Cells and Cancer-Associated Genetic Markers for Peritoneal Recurrence of Colorectal Cancer in Patients after Curative Surgery

Abstract

Objective: The new concept of cancer stem cells has implications in terms of possible application for novel diagnostic and therapeutic procedures. Recently, the CD133 molecule was reported as a marker of cancer stem-like cells in colorectal cancer (CRC). In this study, we examined the prognostic value of free cancer cells in peritoneal washings from CRC patients after curative resection using multiple molecular markers, including cancer stem-like cells. Methods: A total of 170 CRC patients who had undergone curative surgery were studied. Peritoneal washings of the Douglas cavity were collected and used for cytology and molecular diagnosis. Real-time RT-PCR for carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and CD133 mRNA was performed to detect free cancer cells. Results: Molecular detection of CEA, CK20 and/or CD133 (CEA/CK20/CD133) mRNA of the peritoneal washings showed a significant correlation with lymph node metastasis and the tumor stage. The overall survival (OS) rates and peritoneal recurrence-free survival (PFS) rates in CEA/CK20/CD133 mRNA-positive patients were significantly lower than those of marker gene-negative patients. CD133/CEA/CK20 mRNAs in peritoneal washings were independent prognostic factors for OS and PFS. Conclusion: Molecular detection of free cancer cells using multimarkers, including cancer stem-like cells in peritoneal washings of post-curative surgery CRC patients, are useful in prognosis prediction.

CD133, Stem Cells, and Cancer Stem Cells: Myth or Reality?

“…Iinuma showed that peripheral blood CD133 mRNA was the most prognostic when combined with CK and CEA via RT-PCR in 735 stage II and III colorectal cancer patients. Interestingly, CD133 mRNA alone was reportedly not prognostic by Iinuma in stage II and III colorectal cancer, but was prognostic in two other studies that included stage IV patients [71••, 72, 73]. Earlier-stage diseases, small sample size, possibly technical difference, and timing of CD133 mRNA acquisition (preoperative vs postoperative) may explain the differences why CD133 mRNA was not prognostic in the current study.…”

Preliminary Study on the Expression and the Clinical Significance of CD133 in Peripheral Blood of Patients with Gastric Adenocarcinoma

“…Moreover, patients who suffered from deeper invasion were inclined to have a higher level of CD133 mRNA expression after surgery ( P = 0.039). This result was similar to some other reports [28, 29]. Iinuma et al [28] found that the patients with Dukes' B or C of colorectal cancer, who had undergone curative surgery, could possess a higher level of CD133 mRNA in PBMCs.…”

Evaluation of Prognostic Significance of Circulating Tumor Cells Detection in Rectal Cancer Patients Treated with Preoperative Radiotherapy: Prospectively Collected Material Data

“…One of the Fcs of CEA, CK20, and/or CD133 that exceeded cut-off value in patient group indicated the presence of the CTC (CTC (+)), as defined previously in studies by Iinuma [13, 17]. Fc below cut-off value denoted lack of CTC (CTC (−)).…”

“…Previous studies by Nakamura et al [13] and Iinuma et al [11] have shown that expression of CEA/CK20/CD133 mRNA was a useful tool for the detection of CTC in PB of colorectal cancer patients. Based on these studies, we measured the transcriptional levels of three genes: carcinoembryonic antigen [ CEA ], cytokeratin-20 [ CK20 ], and prominin-1 [ CD133 ] by means of qPCR using the relative quantification method (ΔΔCt method) [14].…”