Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1979
Peer-review started: January 7, 2020
First decision: February 19, 2020
Revised: March 26, 2020
Accepted: April 17, 2020
Article in press: April 17, 2020
Published online: April 28, 2020
In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment.
We report six cases of stage IV KRAS-mutated mCRC. Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada. The six patients differed in terms of primary tumor location (right/left side), tumor burden (mostly hepatic and peritoneal disease) and clinical disease course. Before treatment onset, total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures. Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival (under 6 mo) from the start of treatment.
A higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment.
Core tip: Although compared to chemotherapy (CT) alone, bevacizumab-containing CT leads to a significantly better tumor response in metastatic colorectal cancer patients, many do not benefit from this regimen probably due to resistance mechanisms or readjustment of proangiogenic pathways. While CXCL5 expression has been described to predict a poor prognosis in different cancers, its relationship with the efficacy of CT regimens has been scarcely addressed. Our three patients showing CXCL5 higher expression (6 times the levels recorded in the others) showed a poor response in terms of progression-free survival. Our observations provide direction for future studies designed to examine in metastatic colorectal cancer patients treated with bevacizumab-containing therapy, the possible association between CXCL5 gene overexpression and a poor response to treatment with angiogenic drugs.