Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma
BackgroundRenal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leuke...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.934128/full |
| _version_ | 1818010926599634944 |
|---|---|
| author | Wenting Zhong Wenting Zhong Hongxia Liu Feng Li Youyu lin Yan Ye Luyun Xu ShengZhao Li Hui Chen Chengcheng Li Yuxuan Lin Wei Zhuang Yao Lin Qingshui Wang Qingshui Wang |
| author_facet | Wenting Zhong Wenting Zhong Hongxia Liu Feng Li Youyu lin Yan Ye Luyun Xu ShengZhao Li Hui Chen Chengcheng Li Yuxuan Lin Wei Zhuang Yao Lin Qingshui Wang Qingshui Wang |
| author_sort | Wenting Zhong |
| collection | DOAJ |
| description | BackgroundRenal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC.MethodsThe expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database.ResultsThe mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients’ prognosis in different subgroups of ccRCC.ConclusionOur study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision. |
| first_indexed | 2024-04-14T06:01:45Z |
| format | Article |
| id | doaj.art-7775b7c293ab4e3e85e1d44825517e54 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T06:01:45Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-7775b7c293ab4e3e85e1d44825517e542022-12-22T02:08:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.934128934128Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinomaWenting Zhong0Wenting Zhong1Hongxia Liu2Feng Li3Youyu lin4Yan Ye5Luyun Xu6ShengZhao Li7Hui Chen8Chengcheng Li9Yuxuan Lin10Wei Zhuang11Yao Lin12Qingshui Wang13Qingshui Wang14Central Laboratory at the Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaDepartment of Pathology, Fujian Provincial Hospital, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaDepartment of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaCentral Laboratory at the Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCentral Laboratory at the Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Life Sciences, Fujian Normal University, Fuzhou, ChinaBackgroundRenal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC.MethodsThe expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database.ResultsThe mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients’ prognosis in different subgroups of ccRCC.ConclusionOur study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision.https://www.frontiersin.org/articles/10.3389/fonc.2022.934128/fullLIFccRCCWGCNAlassonomograminvasion |
| spellingShingle | Wenting Zhong Wenting Zhong Hongxia Liu Feng Li Youyu lin Yan Ye Luyun Xu ShengZhao Li Hui Chen Chengcheng Li Yuxuan Lin Wei Zhuang Yao Lin Qingshui Wang Qingshui Wang Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma Frontiers in Oncology LIF ccRCC WGCNA lasso nomogram invasion |
| title | Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma |
| title_full | Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma |
| title_fullStr | Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma |
| title_full_unstemmed | Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma |
| title_short | Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma |
| title_sort | elevated expression of lif predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma |
| topic | LIF ccRCC WGCNA lasso nomogram invasion |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.934128/full |
| work_keys_str_mv | AT wentingzhong elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT wentingzhong elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT hongxialiu elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT fengli elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT youyulin elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT yanye elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT luyunxu elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT shengzhaoli elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT huichen elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT chengchengli elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT yuxuanlin elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT weizhuang elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT yaolin elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT qingshuiwang elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma AT qingshuiwang elevatedexpressionoflifpredictsapoorprognosisandpromotescellmigrationandinvasionofclearcellrenalcellcarcinoma |