Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels

Xiaozeng Lin; Yan Gu; Yingying Su; Ying Dong; Pierre Major; Anil Kapoor; Damu Tang

doi:10.3390/cancers14112805

Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels

Cancers (Basel). 2022 Jun 5;14(11):2805. doi: 10.3390/cancers14112805.

Authors

Xiaozeng Lin^{1

2

3}, Yan Gu^{1

2

3}, Yingying Su^{1

2

3}, Ying Dong^{1

2

3}, Pierre Major⁴, Anil Kapoor^{1

2

3}, Damu Tang^{1

2

3}

Affiliations

¹ Urological Cancer Center for Research and Innovation (UCCRI), St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada.
² The Research Institute of St Joe's Hamilton, St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada.
³ Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada.
⁴ Department of Oncology, McMaster University, Hamilton, ON L8V 5C2, Canada.

Abstract

Effective assessment of adrenocortical carcinoma (ACC) prognosis is critical in patient management. We report four novel and robust prognostic multigene panels. Sig27var25, SigIQvar8, SigCmbnvar5, and SigCmbn_B predict ACC relapse at area under the curve (AUC) of 0.89, 0.79, 0.78, and 0.80, respectively, and fatality at AUC of 0.91, 0.88, 0.85, and 0.87, respectively. Among their 33 component genes, 31 are novel. They could be differentially expressed in ACCs from normal tissues, tumors with different severity (stages and lymph node metastasis), ACCs with TP53 mutations, and tumors with differentially expressed immune checkpoints (CTLA4, PD1, TGFBR1, and others). All panels correlate with reductions of ACC-associated CD8+ and/or NK cells. Furthermore, we provide the first evidence for the association of mesenchymal stem cells (MSCs) with ACC relapse (p = 2 × 10^-6) and prognosis (p = 2 × 10^-8). Sig27var25, SigIQvar8, SigCmbnvar5, and SigCmbn_B correlate with MSC (spearman r ≥ 0.53, p ≤ 1.38 × 10^-5). Sig27var25 and SigIQvar8 were derived from a prostate cancer (PC) and clear cell renal cell carcinoma (ccRCC) multigene signature, respectively; SigCmbnvar5 and SigCmbn_B are combinations of both panels, revealing close relationships of ACC with PC and ccRCC. The origin of these four panels from PC and ccRCC favors their prognostic potential towards ACC.

Keywords: adrenocortical carcinoma; disease-free survival; immune checkpoint proteins; mesenchymal stem cells; overall survival; prognostic biomarkers.

Grants and funding

Y.G. is supported by a Postdoctoral Fellowship provided by St Joe’s, Hamilton. Grant support was from the Canadian Cancer Society (grant #: 319412) and CIHR to DT. This research was also supported by funds from the Urological Cancer Centre for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada.