Article Data

  • Views 248
  • Dowloads 115

Original Research

Open Access

A prognostic index model for assessing the prognosis of ccRCC patients by using the mRNA expression profiles of AIF1L, SERPINC1 and CES1

  • Song Zheng1
  • Zihao Chen2
  • Jianhui Chen1
  • Rong Liu1
  • Mei Song3
  • Angchao Ye4
  • Shaoxing Zhu5,6,7
  • Hua Wang5
  • Zongping Wang5
  • Fangyin Li5
  • Jinhan Lou5
  • Yaping Chen5
  • Fang Fang5
  • Chunmei Wen5
  • Jing Zhang5
  • Bilan Xue5
  • He Wang8
  • Jianmin Lou8
  • Weizhong Cai1,*,
  • Yaoyao Wu8,*,
  • Yipeng Xu5,6,7,*,

1Department of Urology, Fujian Medical University Union Hospital, 350001 Fuzhou, Fujian, China

2Department of Urology, Southern Medical University, 510515 Guangzhou, Guangdong, China

3Department of Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 310022 Hangzhou, Zhejiang, China

4Department of Neurology, Integrated Traditional Chinese and Western Medicine Hospital of Linping District, 310005 Hangzhou, Zhejiang, China

5Department of Urology, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 310022 Hangzhou, Zhejiang, China

6The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Chinese Academy of Sciences, 310063 Hangzhou, Zhejiang, China

7Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310063 Hangzhou, Zhejiang, China

8The Second Clinical Medical College, Zhejiang Chinese Medical University, 310059 Hangzhou, Zhejiang, China

DOI: 10.31083/j.jomh1801025 Vol.18,Issue 1,January 2022 pp.1-9

Submitted: 13 October 2021 Accepted: 29 November 2021

Published: 31 January 2022

*Corresponding Author(s): Weizhong Cai E-mail:
*Corresponding Author(s): Yaoyao Wu E-mail:
*Corresponding Author(s): Yipeng Xu E-mail:


Background: Kidney carcinoma is a major cause of carcinoma-related death, with the prognosis for advanced or metastatic renal cell carcinoma still very poor. The aim of this study was to investigate feasible prognostic biomarkers that can be used to construct a prognostic index model for clear cell renal cell carcinoma (ccRCC) patients. Methods: The mRNA expression profiles of ccRCC samples were downloaded from the The Cancer Genome Atlas (TCGA) dataset and the correlation of AIF1L with malignancy, tumor stage and prognosis were evaluated. Differentially expressed genes (DEGs) between AIF1L-low and AIF1L-high expression groups were selected. Those with prognostic value as determined by univariate and multivariate Cox regression analysis were then used to construct a prognostic index model capable of predicting the outcome of ccRCC patients. Results: The expression level of AIF1L was lower in ccRCC samples than in normal kidney samples. AIF1L expression showed an inverse correlation with tumor stage and a positive association with better prognosis. ccRCC samples were divided into high- and low-expression groups according to the median value of AIF1L expression. In the AIF1L-high expression group, 165 up-regulated DEGs and 601 down-regulated DEGs were identified. Three genes (AIF1L, SERPINC1 and CES1) were selected following univariate and multivariate Cox regression analysis. The hazard ratio (HR) and 95% confidence intervals (CI) for these genes were: AIF1L (HR = 0.83, 95% CI: 0.76–0.91), SERPINC1 (HR = 1.33, 95% CI: 1.12–1.58), and CES1 (HR = 0.87, 95% CI: 0.78–0.97). A prognostic index model based on the expression level of the three genes showed good performance in predicting ccRCC patient outcome, with an area under the ROC curve (AUC) of 0.671. Conclusion: This research provides a better understanding of the correlation between AIF1L expression and ccRCC. We propose a novel prognostic index model comprising AIF1L, SERPINC1 and CES1 expression that may assist physicians in determining the prognosis of ccRCC patients.


ccRCC; Prognostic index model; AIF1L; SERPINC1; CES1

Cite and Share

Song Zheng,Zihao Chen,Jianhui Chen,Rong Liu,Mei Song,Angchao Ye,Shaoxing Zhu,Hua Wang,Zongping Wang,Fangyin Li,Jinhan Lou,Yaping Chen,Fang Fang,Chunmei Wen,Jing Zhang,Bilan Xue,He Wang,Jianmin Lou,Weizhong Cai,Yaoyao Wu,Yipeng Xu. A prognostic index model for assessing the prognosis of ccRCC patients by using the mRNA expression profiles of AIF1L, SERPINC1 and CES1. Journal of Men's Health. 2022. 18(1);1-9.


[1] Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, et al. Epidemiology of Renal Cell Carcinoma. European Urology. 2019; 75: 74–84.

[2] Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: an overview. International Journal of Cancer. 2021; 149: 778–789.

[3] Zhou Y, Zhang R, Ding Y, Wang Z, Yang C, Tao S, et al. Prog-nostic nomograms and Aggtrmmns scoring system for predict-ing overall survival and cancer‐specific survival of patients with kidney cancer. Cancer Medicine. 2020; 9: 2710–2722.

[4] Hadoux J, Vignot S, De La Motte Rouge T. Renal Cell Carci-noma: Focus on Safety and Efficacy of Temsirolimus. Clinical Medicine Insights: Oncology. 2010; 4: 143–154.

[5] Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus Ipilimumab ver-sus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2018; 378: 1277–1290.

[6] Powles T, Plimack ER, Soulières D, Waddell T, Stus V, Gafanov R, et al. Pembrolizumab plus axitinib versus sunitinib monother-apy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. The Lancet Oncology. 2020; 21: 1563–1573.

[7] Grünwald V, Hadaschik B. Re: Nivolumab plus Cabozantinib Versus Sunitinib for Advanced Renal-cell Carcinoma. European Urology. 2021; 80: 256–257.

[8] Hindié E. Lenvatinib plus Pembrolizumab for Renal Cell Carci-noma. New England Journal of Medicine. 2021; 385: 287.

[9] Atkins MB, Tannir NM. Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma. Cancer Treatment Reviews. 2018; 70: 127–137.

[10] Makhov P, Joshi S, Ghatalia P, Kutikov A, Uzzo RG, Kolenko VM. Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies. Molecu-lar Cancer Therapeutics. 2018; 17: 1355–1364.

[11] Turajlic S, Xu H, Litchfield K, Rowan A, Chambers T, Lopez JI, et al. Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal. Cell. 2018; 173: 581–594.e12.

[12] Zhang Y, Wang S, Li L. EF Hand Protein IBA2 Promotes Cell Proliferation in Breast Cancers via Transcriptional Control of Cyclin D1. Cancer Research. 2016; 76: 4535–4545.

[13] Jia J, Bai Y, Fu K, Sun Z, Chen X, Zhao Y. Expression of allograft inflammatory factor-1 and CD68 in haemangioma: implication in the progression of haemangioma. British Journal of Dermatology. 2008; 159: 811–819.

[14] Deininger MH, Seid K, Engel S, Meyermann R, Schluesener HJ. Allograft inflammatory factor-1 defines a distinct subset of infiltrating macrophages/microglial cells in rat and human gliomas. Acta Neuropathologica. 2000; 100: 673–680.

[15] Li T, Feng Z, Jia S, Wang W, Du Z, Chen N, et al. Daintain/AIF-1 promotes breast cancer cell migration by up-regulated TNF-α via activate p38 MAPK signaling pathway. Breast Cancer Re-search and Treatment. 2012; 131: 891–898.

[16] Liu S, Tan W, Chen Q, Chen X, Fu K, Zhao Y, et al. Daintain/AIF-1 promotes breast cancer proliferation via acti-vation of the NF-κB/cyclin D1 pathway and facilitates tumor growth. Cancer Science. 2008; 99: 952–957.

[17] Jia J, Cai Y, Wang R, Fu K, Zhao Y. Overexpression of Allo-graft Inflammatory Factor-1 Promotes the Proliferation and Mi-gration of Human Endothelial Cells (HUV-EC-C) Probably by up-Regulation of Basic Fibroblast Growth Factor. Pediatric Re-search. 2010; 67: 29–34.

[18] Ye Y, Miao S, Lu R, Xia X, Chen Y, Zhang J, et al. Allograft in-flammatory factor-1 is an independent prognostic indicator that regulates β-catenin in gastric cancer. Oncology Reports. 2014; 31: 828–834.

[19] Schulze JO, Quedenau C, Roske Y, Adam T, Schüler H, Behlke J, et al. Structural and functional characterization of human Iba proteins. FEBS Journal. 2008; 275: 4627–4640.

[20] Chen ZW, Ahren B, Ostenson CG, Cintra A, Bergman T, Moller C, et al. Identification, isolation, and characterization of dain-tain (allograft inflammatory factor 1), a macrophage polypep-tide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats. Proceedings of the National Academy of Sciences. 1997; 94: 13879–13884.

[21] Shyamsundar R, Kim YH, Higgins JP, Montgomery K, Jorden M, Sethuraman A, et al. A DNA microarray survey of gene ex-pression in normal human tissues. Genome Biology. 2005; 6: R22.

[22] Autieri MV. CDNA Cloning of Human Allograft Inflammatory Factor-1: Tissue Distribution, Cytokine Induction, and mRNA Expression in Injured Rat Carotid Arteries. Biochemical and Biophysical Research Communications. 1996; 228: 29–37.

[23] Utans U, Arceci RJ, Yamashita Y, Russell ME. Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic rejection. Journal of Clinical Investigation. 1995; 95: 2954–2962.

[24] Wozniak MB, Le Calvez-Kelm F, Abedi-Ardekani B, Byrnes G, Durand G, Carreira C, et al. Integrative genome-wide gene ex-pression profiling of clear cell renal cell carcinoma in Czech Re-public and in the United States. PLoS ONE. 2013; 8: e57886.

[25] Robinson MD, McCarthy DJ, Smyth GK. EdgeR: a Bioconduc-tor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010; 26: 139–140.

[26] Lin H, Chen L, Li W, Chen Z. Novel Therapies for Tongue Squa-mous Cell Carcinoma Patients with High-Grade Tumors. Life. 2021; 11: 813.

[27] Yu G, Wang LG, Han Y, He QY. ClusterProfiler: an R Pack-age for Comparing Biological Themes among Gene Clusters. OMICS. 2012; 16: 284–287.

[28] Lin H, Zelterman D. Modeling Survival Data: Extending the Cox Model. Technometrics. 2002; 44: 85–86.

[29] Xu W, Xu Y, Wang J, Wan F, Wang H, Cao D, et al. Prognostic value and immune infiltration of novel signatures in clear cell renal cell carcinoma microenvironment. Aging. 2019; 11: 6999–7020.

[30] Ganesh K, Massagué J. Targeting metastatic cancer. Nature Medicine. 2021; 27: 34–44.

[31] Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochimica et Biophysica Acta-Molecular Cell Research. 2007; 1773: 642–652.

[32] Yasuda-Yamahara M, Rogg M, Yamahara K, Maier JI, Hu-ber TB, Schell C. AIF1L regulates actomyosin contractility and filopodial extensions in human podocytes. PLoS ONE. 2018; 13: e200487.

[33] Arjonen A, Kaukonen R, Ivaska J. Filopodia and adhesion in cancer cell motility. Cell Adhesion & Migration. 2014; 5: 421–430.

[34] Liu P, Li W, Hu Y, Jiang Y. Absence of AIF1L contributes to cell migration and a poor prognosis of breast cancer. OncoTargets and Therapy. 2018; 11: 5485–5498.

[35] Caspers M, Pavlova A, Driesen J, Harbrecht U, Klamroth R, Kadar J, et al. Deficiencies of antithrombin, protein C and pro-tein S –Practical experience in genetic analysis of a large patient cohort. Thrombosis and Haemostasis. 2017; 108: 247–257.

[36] Xu J, Ying Y, Xiong G, Lai L, Wang Q, Yang Y. Knockdown of serpin peptidase inhibitor clade C member 1 inhibits the growth of nasopharyngeal carcinoma cells. Molecular Medicine Re-ports. 2019; 19: 3658–3666.

[37] Ura B, Biffi S, Monasta L, Arrigoni G, Battisti I, Di Lorenzo G, et al. Two Dimensional-Difference in Gel Electrophoresis (2D-DIGE) Proteomic Approach for the Identification of Biomarkers in Endometrial Cancer Serum. Cancers. 2021; 13: 3639.

[38] Zhao M, Li M, Chen Z, Bian Y, Zheng Y, Hu Z, et al. Identi-fication of immune-related gene signature predicting survival in the tumor microenvironment of lung adenocarcinoma. Immuno-genetics. 2020; 72: 455–465.

[39] Xie J, Wu Z, Xu X, Liang G, Xu J. Screening and identification of key genes and pathways in metastatic uveal melanoma based on gene expression using bioinformatic analysis. Medicine. 2020; 99: e22974.

[40] Xu X, Zhou Y, Miao R, Chen W, Qu K, Pang Q, et al. Transcrip-tional modules related to hepatocellular carcinoma survival: co-expression network analysis. Frontiers of Medicine. 2016; 10: 183–190.

[41] Taketani M, Shii M, Ohura K, Ninomiya S, Imai T. Car-boxylesterase in the liver and small intestine of experimental animals and human. Life Sciences. 2007; 81: 924–932.

[42] Ke CC, Chen LC, Yu CC, Cheng WC, Huang CY, Lin VC, et al. Genetic Analysis Reveals a Significant Contribution of CES1 to Prostate Cancer Progression in Taiwanese Men. Cancers. 2020; 12: 1346.

[43] McCormick JA, Markey GM, Morris TCM, Auld PW, Alexan-der HD. Lactoferrin inducible monocyte cytotoxicity defective in esterase deficient monocytes. British Journal of Haematology. 1991; 77: 287–290.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Directory of Open Access Journals (DOAJ) DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.

SCImago The SCImago Journal & Country Rank is a publicly available portal that includes the journals and country scientific indicators developed from the information contained in the Scopus® database (Elsevier B.V.)

Publication Forum - JUFO (Federation of Finnish Learned Societies) Publication Forum is a classification of publication channels created by the Finnish scientific community to support the quality assessment of academic research.

Scopus CiteScore 0.7 (2021) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Norwegian Register for Scientific Journals, Series and Publishers Search for publication channels (journals, series and publishers) in the Norwegian Register for Scientific Journals, Series and Publishers to see if they are considered as scientific. (

Submission Turnaround Time