Impact of neoadjuvant concurrent chemoradiation on exosomal markers expression in colorectal cancer

Reviewed by Emily Henderson, B.Sc.Sep 1 2021

Oncotarget published "The impact of neoadjuvant concurrent chemoradiation on exosomal markers (CD63 and CD9) expression and their prognostic significance in patients with rectal adenocarcinoma" which reported that the impact of neoadjuvant concurrent chemoradiation on exosomal markers expression and their prognostic significance in patients with rectal adenocarcinoma are yet to be explored.

The mean tumor CD63 and CD9 scores in pre-NCCR biopsy vs. post-NCCR resected rectum were 106 vs. 165 and 136 vs. 215 respectively.

The mean tumor CD63 and CD9 scores respectively in pre-NCCR biopsy was 99 and 130 in patients with low-intermediate NAR scores compared to 117 and 144 in patients with high NAR scores.

The mean tumor CD63 and CD9 scores respectively in post-NCCR resected rectum was 155 and 205 in patients with low-intermediate NAR scores compared to 180 and 230 in patients with high NAR scores.

There was a trend for higher CD63 and CD9 expression in patients with high NAR scores compared with low-intermediate NAR scores.

Colorectal cancer (CRC) is a common disease."

Dr. Moh'd Khushman, The O'Neal Comprehensive Cancer Center

Tumor response to neoadjuvant therapy may predict long-term outcomes such as disease-free survival and overall survival.

Radiation-derived exosomes promoted proliferation and helped recipient cancer cells to survive the radiation in vitro and decreased the survival of tumor-bearing mice in vivo.

Chemotherapy-induced exosomes have been shown to carry different cargo loads compared to no-chemotherapy-induced exosomes.

Calculating the NAR score is performed using tumor variables before and after treatment with neoadjuvant therapy including the clinical T, the pathological T, and pathological N stages using the formula.

The NAR score was validated using the patient dataset from NSABP R-04 clinical trial where NAR scores were categorized as low, intermediate, and high.

The Khushman Research Team concluded that this study has several limitations.

This is also a retrospective study that is prone to selection bias and provides an inferior level of evidence compared to prospective studies.

Moreover, the method of exosomal markers detection used in this study is IHC.

Apart from providing data about exosomal markers expression, IHC staining doesn't provide data about the origin of exosomes and their function and content.

Despite the demonstrated impact of concurrent chemotherapy and radiation on the expression of CD63 and CD9 and their possible prognostic significance, these results and conclusions should be interpreted with caution and rather considered hypothesis-generating.

Studies that can address our limitations and of larger cohorts need to be conducted to confirm the results and explore the underlying mechanisms.