The impact of neoadjuvant concurrent chemoradiation on exosomal markers (CD63 and CD9) expression and their prognostic significance in patients with rectal adenocarcinoma
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Moh’d Khushman1, Pranitha Prodduturvar2, Wadad Mneimneh3, Valeria Dal Zotto4, Shalla Akbar4, Leander Grimm5, Paul Rider5, John Hunter5, Omar Alkharabsheh1, Girijesh Kumar Patel6, Jesus C. Fabregas7 and Ajay P. Singh4
1 Hematology-Oncology, O’Neal Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA
2 Medical Oncology, Mayo Clinic, Rochester, MN, USA
3 Pathology, Case Western Reserve University, Cleveland, OH, USA
4 Pathology, The University of South Alabama, Mobile, AL, USA
5 Colorectal Surgery, The University of South Alabama, Mobile, AL, USA
6 Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA
7 Harvard T.H. Chan School of Public Health, Boston, MA, USA
Keywords: exosomes; exosomal markers; CD63; CD9; neoadjuvant chemoradiation
Received: April 21, 2021 Accepted: June 22, 2021 Published: July 20, 2021
Introduction: Exosomes have pivotal roles in cancer development. The impact of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression and their prognostic significance in patients with rectal adenocarcinoma are yet to be explored.
Materials and Methods: Between 2015 and 2018, 33 patients had rectal adenocarcinoma treated with NCCR and had pre-NCCR biopsy and post-NCCR resected rectum. CD63 and CD9 expression was assessed by immunohistochemistry (IHC). The short-term surrogate endpoint neoadjuvant rectal (NAR) score was used for assessment of prognostic significance. Un-Paired t-test was used for statistical analysis.
Results: The mean tumor CD63 and CD9 scores in pre-NCCR biopsy vs. post-NCCR resected rectum were 106 vs. 165 (P = 0.0022) and 136 vs. 215 (P < 0.0001) respectively. The mean tumor CD63 and CD9 scores respectively in pre-NCCR biopsy was 99 and 130 in patients with low-intermediate NAR score compared to 117 and 144 in patients with high NAR score (P = 0.4934) (P = 0.5519). The mean tumor CD63 and CD9 scores respectively in post-NCCR resected rectum was 155 and 205 in patients with low-intermediate NAR score compared to 180 and 230 in patients with high NAR score (P = 0.3793) (P = 0.2837).
Conclusions: The expression of the exosomal markers (CD63 and CD9) increased in patients with rectal adenocarcinoma after treatment with NCCR. The exosomal markers (CD63 and CD9) may have a prognostic significance. There was a trend for higher CD63 and CD9 expression in patients with high NAR score compared with low-intermediate NAR scores. The lack of statistical significance is likely due to the small sample size.
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