Abstract
Abstract Objectives The recurrence of rectal cancer or its resistance to neoadjuvant treatment develops due to the adaptation to hypoxia, apoptosis or autophagy. Survivin, one of the inhibitors of apoptosis; Beclin 1, which is a positive regulator in the autophagy pathway; and hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase-9 (CA9), which are associated with tumor tissue hypoxia, may be related to resistance to treatment. Our aim was to evaluate the potential tumor markers that may help to monitor the response to neoadjuvant treatment in locally advanced rectal cancer (RC). Methods Twenty-five patients with locally advanced RC were included in the study. Gene expression and protein levels of Beclin 1, Survivin, HIF-1α, and CA9 were analyzed in fresh tissue specimens and blood samples. The relationships of these markers to tumor staging and regression grade were evaluated. Results Higher blood CA9 gene expression levels and lower blood HIF-1α protein levels were found in the response group according to tumor regression grade. After neoadjuvant treatment, tissue Beclin 1 and blood Survivin gene expressions and tissue CA9, blood Beclin 1 and blood HIF-1α protein levels decreased significantly. Conclusion Beclin 1, Survivin, HIF-1α ve CA9 may help to predict the effects of the applied treatment approach.
Highlights
Rectal cancer (RC) is one of the highest morbidity- and mortality-causing factors in humans worldwide [1]
Diniz) Dilek Oncel, Radiology Clinic, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey Mustafa Degirmenci, Oncology Clinic, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey Bulent Ozkan, Department of Biostatistics, Faculty of Medicine, Katip Çelebi University, Izmir, Turkey inducible factor-1α (HIF-1α) and carbonic anhydrase-9 (CA9), which are associated with tumor tissue hypoxia, may be related to resistance to treatment
36% of the patients had downstaging according to the T stage, and 72% of them had downstaging according to the N stage
Summary
Rectal cancer (RC) is one of the highest morbidity- and mortality-causing factors in humans worldwide [1]. Radical surgery is the main RC treatment approach, but neoadjuvant treatments can be considered as a complementary approach. 8–20% of RC patients had a complete response, 30–60% had a partial response, and the remainder had resistance to treatment [2, 3]. Cell death was the aim of these treatments. Resistance to apoptosis is an important factor responsible for inadequate treatment and relapse in gastrointestinal oncology. There is a regulatory association between apoptosis and autophagy. Combined treatments that include apoptotic and autophagic mechanisms, have been investigated in order to overcome cell death resistance in RC [4,5,6]
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