IMR Press / EJGO / Volume 40 / Issue 5 / DOI: 10.12892/ejgo4902.2019
Open Access Original Research
GCDH contributes to better outcome and acts on chemoresistance and immune exclusion in cervical cancer
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1 Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China
2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of China, University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China;
Eur. J. Gynaecol. Oncol. 2019, 40(5), 831–838; https://doi.org/10.12892/ejgo4902.2019
Published: 10 October 2019
Abstract

Aim: Cervical cancer is a major health problem in women and its genetic culprit remains inclusive. The authors aim to evaluate the role of glutaryl-CoA dehydrogenase (GCDH) in cervical cancer. Materials and Methods: Clinicopathological attribution of GCDH was queried in silico using the human cancer genome atlas project (TCGA) and HPA database. In vitro studies using cell lines and nude mice were used to examine the therapeutic potential of targeting GCDH. Results: GCDH expression was significantly higher in cancer tissue compared with normal cervical tissue. Cervical cancer patients with overexpressed GCDH had significantly better overall survival. Functional annotation indicated enrichment in cell-cycle regulatory pathway. Knockdown (KD) and overexpression (OE) of GCDH-induced increased and decreased proliferation, respectively. Similar results were also obtained in cell-cycle arrest, invasion, migration, and colony formation assays, but having no effect on cell apoptosis. To understand the selection advantage of GCHD-overexpressed cases, the authors analyzed immunological profile in silico. Expression of GCDH correlated with that of IDO2, which was significantly associated with decreased immunity. GCDH-KD-induced decreased expression of IDO2, which also led to decreased kynurenine and tryptophan in culturing media. GCDH-OE promoted chemoresistance in cervical cancer cells due to cell-cycle arrest. GCDH-OE also significantly inhibited tumor growth in vivo yet showed partial resistance to chemotherapy, with increased level of IDO2 expression. Conclusion: GCDH is overexpressed in cervical cancer and represents a less aggressive phenotype of disease, which is also characterized with increased chemoresistance and immune exclusion. Inhibition of IDO2 could be of therapeutic potential.

Keywords
Cervical cancer
GCDH
Chemoresistance
Immune exclusion
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