@Article{096504021X16232280278813,
AUTHOR = {Chiara Dalle Fratte, Silvia Mezzalira, Jerry Polesel, Elena De Mattia, Antonio Palumbo, Angela Buonadonna, Elisa Palazzari, Antonino De Paoli, Claudio Belluco, Vincenzo Canzonieri, Giuseppe Toffoli, Erika Cecchin},
TITLE = {A Panel of Tumor Biomarkers to Predict Complete Pathological Response  to Neoadjuvant Treatment in Locally Advanced Rectal Cancer},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {9},
PAGES = {847--855},
URL = {http://www.techscience.com/or/v28n9/48480},
ISSN = {1555-3906},
ABSTRACT = {Pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients 
is related to a favorable prognosis. The identification of early biomarkers predictive of pathological complete 
response would help optimize the multimodality management of the patients. A panel of 11 tumor-related 
proteins was investigated by immunohistochemistry in the pretreatment biopsy of a group of locally advanced 
rectal cancer patients to identify early biomarkers of pathological complete response to neoadjuvant chemoradiotherapy. A mono-institutional retrospective cohort of 95 stage II/III locally advanced rectal cancer patients 
treated with neoadjuvant chemoradiotherapy and surgery was selected based on clinical–pathological characteristics and the availability of a pretreatment tumor biopsy. Eleven selected protein marker expression (MLH1, 
GLUT1, Ki67, CA-IX, CXCR4, COX2, CXCL12, HIF1a, VEGF, CD44, and RAD51) was investigated. The 
optimal cutoff values were calculated by receiver operating characteristic curve analysis. Classification and 
regression tree analysis was performed to investigate the biomarker interaction. Patients presenting either Ki-67 
or HIF1a or RAD51 below the cutoff value, or CXCR4 or COX2 above the cutoff value, were more likely 
to get a pathological complete response. Classification and regression tree analysis identified three groups of 
patients resulting from the combination of Ki-67 and CXCR4 expression. Patients with high expression of 
Ki-67 had the lowest chance to get a pathological complete response (18%), as compared to patients with low 
expression of both Ki-67 and CXCR4 (29%), and patients with low Ki-67 and high CXCR4 expression (70%). 
Pretreatment Ki-67, CXCR4, COX2, HIF1a, and RAD51 in tumor biopsies are associated with pathological 
complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. A combined evaluation of Ki-67 and CXCR4 would increase their predictive potential. If validated, their optimal cutoff could be 
used to select patients for a tailored multimodality treatment.},
DOI = {10.3727/096504021X16232280278813}
}