Min Zhou1, Bingshu Li1, Jianfeng Liu1, Li Hong1. 1. Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Abstract
PURPOSE: Pyroptosis is a form of lytic programmed cell death that is associated with the pathogenesis of many tumors. However, the potential roles of pyroptosis-related genes (PRGs) in the tumor microenvironment (TME) remain unclear. MATERIALS AND METHODS: We systematically described the genetic and transcriptional alterations in PRGs in gynecological cancers. An unsupervised clustering method was used to investigate the molecular subtypes of ovarian cancer (OV) and systematically analyze the TME cell infiltration characteristics. A prognostic signature and nomogram were established to quantify the pyroptosis patterns of individual tumors. We also analyzed the expression levels of eight PRGs in the OV tissues. RESULTS: Two distinct molecular subtypes of OV were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, immune infiltrating cells, and immune checkpoints. A prognostic signature was established, and its predictive capability was validated. Low risk score, characterized by activation of immunity, upregulation of programmed death-ligand 1 expression, lower tumor immune dysfunction and exclusion scores, lower tumor mutation burden, and favorable prognosis. These findings suggested that low-risk patients with OV may be more sensitive to immunotherapy. In addition, this signature could effectively predict the response to chemotherapy in patients with OV. Furthermore, a prognostic nomogram was generated, which exhibited superior predictive accuracy. CONCLUSION: This study highlights the crucial role of PRGs in the TME and may help develop immunotherapies and promote individualized therapeutic strategies for patients with OV.
PURPOSE: Pyroptosis is a form of lytic programmed cell death that is associated with the pathogenesis of many tumors. However, the potential roles of pyroptosis-related genes (PRGs) in the tumor microenvironment (TME) remain unclear. MATERIALS AND METHODS: We systematically described the genetic and transcriptional alterations in PRGs in gynecological cancers. An unsupervised clustering method was used to investigate the molecular subtypes of ovarian cancer (OV) and systematically analyze the TME cell infiltration characteristics. A prognostic signature and nomogram were established to quantify the pyroptosis patterns of individual tumors. We also analyzed the expression levels of eight PRGs in the OV tissues. RESULTS: Two distinct molecular subtypes of OV were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, immune infiltrating cells, and immune checkpoints. A prognostic signature was established, and its predictive capability was validated. Low risk score, characterized by activation of immunity, upregulation of programmed death-ligand 1 expression, lower tumor immune dysfunction and exclusion scores, lower tumor mutation burden, and favorable prognosis. These findings suggested that low-risk patients with OV may be more sensitive to immunotherapy. In addition, this signature could effectively predict the response to chemotherapy in patients with OV. Furthermore, a prognostic nomogram was generated, which exhibited superior predictive accuracy. CONCLUSION: This study highlights the crucial role of PRGs in the TME and may help develop immunotherapies and promote individualized therapeutic strategies for patients with OV.
Authors: Peng Jiang; Shengqing Gu; Deng Pan; Jingxin Fu; Avinash Sahu; Xihao Hu; Ziyi Li; Nicole Traugh; Xia Bu; Bo Li; Jun Liu; Gordon J Freeman; Myles A Brown; Kai W Wucherpfennig; X Shirley Liu Journal: Nat Med Date: 2018-08-20 Impact factor: 53.440
Authors: Kyle C Strickland; Brooke E Howitt; Sachet A Shukla; Scott Rodig; Lauren L Ritterhouse; Joyce F Liu; Judy E Garber; Dipanjan Chowdhury; Catherine J Wu; Alan D D'Andrea; Ursula A Matulonis; Panagiotis A Konstantinopoulos Journal: Oncotarget Date: 2016-03-22