Identification of DDX60 as a Regulator of MHC-I Class Molecules in Colorectal Cancer

Nina Geng; Tuo Hu; Chunbo He

doi:10.3390/biomedicines10123092

Identification of DDX60 as a Regulator of MHC-I Class Molecules in Colorectal Cancer

Biomedicines. 2022 Dec 1;10(12):3092. doi: 10.3390/biomedicines10123092.

Authors

Nina Geng^{1

2}, Tuo Hu^{1

3}, Chunbo He¹

Affiliations

¹ Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
² Collège Jean-de-Brébeuf, Montréal, QC H3T 1C1, Canada.
³ Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China.

Abstract

Immune checkpoint blockade (ICB) therapies induce durable responses in approximately 15% of colorectal cancer (CRC) patients who exhibit microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). However, more than 80% of CRC patients do not respond to current immunotherapy. The main challenge with these patients is lack of MHC-I signaling to unmask their cancer cells so the immune cells can detect them. Here, we started by comparing IFNγ signature genes and MHC-I correlated gene lists to determine the potential candidates for MHC-I regulators. Then, the protein expression level of listed potential candidates in normal and cancer tissue was compared to select final candidates with enough disparity between the two types of tissues. ISG15 and DDX60 were further tested by wet-lab experiments. Overexpression of DDX60 upregulated the expression of MHC-I, while knockdown of DDX60 reduced the MHC-I expression in CRC cells. Moreover, DDX60 was downregulated in CRC tissues, and lower levels of DDX60 were associated with a poor prognosis. Our data showed that DDX60 could regulate MHC-I expression in CRC; thus, targeting DDX60 may improve the effects of immunotherapy in some patients.

Keywords: DDX60; MHC-I; colorectal cancer; immunotherapy.

Grants and funding

This work was supported by the Fred & Pamela Buffett Cancer Center (no number). Tuo Hu is supported by the China Scholarship Council, the Starting Funding of Faculty from Sun Yat-sen University (No. 2021276), and National Key Clinical Discipline.