TY - JOUR
TI - Membranous CD44v6 is upregulated as an early event in colorectal cancer:
Downregulation is associated with circulating tumor cells and poor
prognosis
AU - Kataki, Agapi
AU - Giannakoulis, Vassilis G.
AU - Derventzi, Anastasia and
AU - Papiris, Konstantinos
AU - Koniaris, Eythimios
AU - Konstadoulakis,
AU - Manousos
JO - Oncology Letters
PY - 2021
VL - 22
TODO - 6
SP - null
PB - SPANDIDOS PUBL LTD
SN - 1792-1074, 1792-1082
TODO - 10.3892/ol.2021.13081
TODO - membranous CD44 variant 6; metastasis-associated protein 1; circulating
tumor cells; polyps; colorectal cancer; tumor microenvironment
TODO - Previous studies have reported that CD44 variant 6 (CD44v6) and
metastasis-associated protein 1 (MTA1) are contributing factors to
cancer progression. The present study aimed to evaluate the expression
profiles for associations with patients' demographic data,
clinicopathological characteristics, the presence of partial
epithelial-to-mesenchymal transition (pEMT), metastatic potential based
on the presence of CK20(+) CEA(+) CXCR4(+) circulating tumor cells
(CTCs) and prognosis (median follow-up, 45 months). Thus, frozen tissue
samples from 31 patients with stage I-III colorectal cancer (CRC), 15
benign colorectal polyps and seven normal colorectal tissues were
analyzed to detect membranous (m)CD44v6 and MTA1 expression via flow
cytometry. The results demonstrated that the mCD44v6 and MTA1 expression
profiles were significantly correlated (r(s)=+0.786, P<0.001). Notably,
MTA1 expression was not associated with any of the clinicopathological
characteristics assessed. The percentage of mCD44v6-positive cells
within tumors was higher in the right-sided cancer lesions (P=0.014),
suggesting that proximal and distal CRCs are distinct
clinicopathological entities. Furthermore, downregulated mCD44v6
expression was significantly associated with the presence of CTCs
(P=0.017). This association was stronger for pEMT (co-expression of N-
and E-cadherin mRNAs) primary lesions (P=0.009). In addition, patients
with CRC with low levels of mCD44v6 had unfavorable survival outcomes
(P=0.037). Taken together, these results suggest that targeted analysis
of membranous CD44v6 as opposed to membranous-cytoplasmic expression is
important in determining the prognosis of patients with CRC.
Furthermore, downregulated mCD44v6 expression in malignancies presenting
CTCs reinforces the importance of tumor-stroma reciprocal influence
during the metastatic process and encourages the assessment of relevant
therapeutic strategies.
ER -