Xiaoqing Luo1, Shunli Peng1, Sijie Ding1, Qin Zeng1, Rong Wang1, Yueyun Ma1, ShiYu Chen1, Yanxia Wang1, Wei Wang2. 1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China. 2. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China. wangwei9500@hotmail.com.
Abstract
BACKGROUND: Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. METHODS: SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan-Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. RESULTS: SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. CONCLUSIONS: This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.
BACKGROUND: Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. METHODS:SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on humanNSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan-Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. RESULTS:SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. CONCLUSIONS: This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.
Authors: Irene Ferrer; Jon Zugazagoitia; Stephan Herbertz; William John; Luis Paz-Ares; Gerald Schmid-Bindert Journal: Lung Cancer Date: 2018-07-19 Impact factor: 5.705
Authors: K Scheffzek; M R Ahmadian; W Kabsch; L Wiesmüller; A Lautwein; F Schmitz; A Wittinghofer Journal: Science Date: 1997-07-18 Impact factor: 47.728
Authors: Pasi A Jänne; James Chih-Hsin Yang; Dong-Wan Kim; David Planchard; Yuichiro Ohe; Suresh S Ramalingam; Myung-Ju Ahn; Sang-We Kim; Wu-Chou Su; Leora Horn; Daniel Haggstrom; Enriqueta Felip; Joo-Hang Kim; Paul Frewer; Mireille Cantarini; Kathryn H Brown; Paul A Dickinson; Serban Ghiorghiu; Malcolm Ranson Journal: N Engl J Med Date: 2015-04-30 Impact factor: 91.245