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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Kidney Cancer | Research

CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma

Authors: Hui-feng Wu, Hao Liu, Zhe-wei Zhang, Ji-min Chen

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Background

Most sarcomatoid differentiated renal cell carcinoma was differentiated from Chromophobe renal cell carcinoma (KICH) and related to a bad prognosis. Thus, finding biomarkers is important for the therapy of KICH.

Methods

The UCSC was used for determining the expression of mRNA and miRNA and clinical data in KICH and normal samples. KEGG and GO were used for predicting potential function of differently expressed genes (DEGs). Optimal prognostic markers were determined by Lasso regression. Kaplan–Meier survival, ROC, and cox regression were used for assessing prognosis value. GSEA was used for predicting potential function of markers. The relations between markers and immune cell infiltration were determined by Pearson method. The upstream miRNA of markers was predicted in TargetScan and DIANA.

Results

The 6162 upregulated and 13,903 downregulated DEGs were identified in KICH. Further CENPE and LDHA were screened out as optimal prognostic risk signatures. CENPE was highly expressed while LDHA was lowly expressed in KICH samples, and the high expressions of 2 genes contributed to bad prognosis. The functions of CENPE and LDHA were mainly enriched in proliferation related pathways such as cell cycle and DNA replication. In addition, the correlation of 2 genes with immune infiltrates in KICH was also observed. Finally, we found that has-miR-577 was the common upstream of 2 genes and the binding sites can be predicted.

Conclusion

CENPE and LDHA were identified as the important prognostic biomarkers in KICH, and they might be involved in the proliferation of cancer cell.
Literature
1.
Roldan-Romero JM, Santos M, Lanillos J, Caleiras E, Anguera G, Maroto P, et al. Molecular characterization of chromophobe renal cell carcinoma reveals mTOR pathway alterations in patients with poor outcome. Mod Pathol. 2020;33(12):2580–90.PubMedCrossRef
2.
Alaghehbandan R, Trpkov K, Tretiakova M, Luis AS, Rogala JD, Hes O. Comprehensive review of numerical chromosomal aberrations in chromophobe renal cell carcinoma including its variant morphologies. Adv Anat Pathol. 2021;28(1):8–20.PubMedCrossRef
3.
Linehan WM, Ricketts CJ. The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications. Nat Rev Urol. 2019;16(9):539–52.PubMedCrossRef
4.
Paule B, Brion N. Temsirolimus in metastatic chromophobe renal cell carcinoma after interferon and sorafenib therapy. Anticancer Res. 2011;31(1):331–3.PubMed
5.
Agrawal R, Kaushal K. Attention and short-term memory in normal children, aggressive children, and non-aggressive children with attention-deficit disorder. J Gen Psychol. 1987;114(4):335–44.PubMedCrossRef
6.
Li X, Ma C. Alpha-2-Heremans-Schmid-glycoprotein (AHSG) a potential biomarker associated with prognosis of chromophobe renal cell carcinoma: the PROPOLIS study. Health Sci Rep. 2022;5(6):e878.PubMedPubMedCentralCrossRef
7.
Klatte T, Han KR, Said JW, Bohm M, Allhoff EP, Kabbinavar FF, et al. Pathobiology and prognosis of chromophobe renal cell carcinoma. Urol Oncol. 2008;26(6):604–9.PubMedCrossRef
8.
Shan L, Zhao M, Lu Y, Ning H, Yang S, Song Y, et al. CENPE promotes lung adenocarcinoma proliferation and is directly regulated by FOXM1. Int J Oncol. 2019;55(1):257–66.PubMed
9.
Zhu X, Luo X, Feng G, Huang H, He Y, Ma W, et al. CENPE expression is associated with its DNA methylation status in esophageal adenocarcinoma and independently predicts unfavorable overall survival. PLoS ONE. 2019;14(2):e0207341.PubMedPubMedCentralCrossRef
10.
Li Y, Shi Y, Wang X, Yu X, Wu C, Ding S. Silencing of CHFR sensitizes gastric carcinoma to PARP inhibitor treatment. Transl Oncol. 2020;13(1):113–21.PubMedCrossRef
11.
Ma C, Wang J, Zhou J, Liao K, Yang M, Li F, et al. CENPE promotes glioblastomas proliferation by directly binding to WEE1. Transl Cancer Res. 2020;9(2):717–25.PubMedPubMedCentralCrossRef
12.
Li TF, Zeng HJ, Shan Z, Ye RY, Cheang TY, Zhang YJ, et al. Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer. Cancer Cell Int. 2020;20:123.PubMedPubMedCentralCrossRef
13.
Wang Q, Xu J, Xiong Z, Xu T, Liu J, Liu Y, et al. CENPA promotes clear cell renal cell carcinoma progression and metastasis via Wnt/beta-catenin signaling pathway. J Transl Med. 2021;19(1):417.PubMedPubMedCentralCrossRef
14.
Huo N, Cong R, Sun ZJ, Li WC, Zhu X, Xue CY, et al. STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis. Cell Death Dis. 2021;12(9):799.PubMedPubMedCentralCrossRef
15.
Feng Y, Xiong Y, Qiao T, Li X, Jia L, Han Y. Lactate dehydrogenase A: a key player in carcinogenesis and potential target in cancer therapy. Cancer Med. 2018;7(12):6124–36.PubMedPubMedCentralCrossRef
16.
Wang C, Li Y, Yan S, Wang H, Shao X, Xiao M, et al. Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2. Nat Commun. 2020;11(1):3162.PubMedPubMedCentralCrossRef
17.
Shi L, An S, Liu Y, Liu J, Wang F. PCK1 regulates glycolysis and tumor progression in clear cell renal cell carcinoma through LDHA. Onco Targets Ther. 2020;13:2613–27.PubMedPubMedCentralCrossRef
18.
Lei T, Qian H, Lei P, Hu Y. Ferroptosis-related gene signature associates with immunity and predicts prognosis accurately in patients with osteosarcoma. Cancer Sci. 2021;112(11):4785–98.PubMedPubMedCentralCrossRef
19.
Zhang C, Zhang M, Ge S, Huang W, Lin X, Gao J, et al. Reduced m6A modification predicts malignant phenotypes and augmented Wnt/PI3K-Akt signaling in gastric cancer. Cancer Med. 2019;8(10):4766–81.PubMedPubMedCentralCrossRef
20.
Dai X, Lu L, Deng S, Meng J, Wan C, Huang J, et al. USP7 targeting modulates anti-tumor immune response by reprogramming tumor-associated macrophages in lung cancer. Theranostics. 2020;10(20):9332–47.PubMedPubMedCentralCrossRef
21.
22.
Hao X, Qu T. Expression of CENPE and its prognostic role in non-small cell lung cancer. Open Med (Wars). 2019;14:497–502.PubMedCrossRef
23.
Scaife RM. G2 cell cycle arrest, down-regulation of cyclin B, and induction of mitotic catastrophe by the flavoprotein inhibitor diphenyleneiodonium. Mol Cancer Ther. 2004;3(10):1229–37.PubMedCrossRef
24.
25.
Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-kinase, growth disorders, and cancer. N Engl J Med. 2018;379(21):2052–62.PubMedCrossRef
26.
Shi M, Niu J, Niu X, Guo H, Bai Y, Shi J, et al. Lin28A/CENPE promoting the proliferation and chemoresistance of acute myeloid leukemia. Front Oncol. 2021;11: 763232.PubMedPubMedCentralCrossRef
27.
Wang J, Dai W, Zhang M. E2F1 induced neuroblastoma cell migration and invasion via activation of CENPE/FOXM1 signaling pathway. Int J Neurosci. 2022;1–13.
28.
di Meo NA, Lasorsa F, Rutigliano M, Milella M, Ferro M, Battaglia M, et al. The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery. Expert Rev Mol Diagn. 2023;23(4):297–313.PubMedCrossRef
29.
Lucarelli G, Loizzo D, Franzin R, Battaglia S, Ferro M, Cantiello F, et al. Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma. Expert Rev Mol Diagn. 2019;19(5):397–407.PubMedCrossRef
30.
di Meo NA, Lasorsa F, Rutigliano M, Loizzo D, Ferro M, Stella A, et al. Renal cell carcinoma as a metabolic disease: an update on main pathways, potential biomarkers, and therapeutic targets. Int J Mol Sci. 2022;23(22):14360.PubMedPubMedCentralCrossRef
31.
De Marco S, Torsello B, Minutiello E, Morabito I, Grasselli C, Bombelli S, et al. The cross-talk between Abl2 tyrosine kinase and TGFbeta1 signalling modulates the invasion of clear cell renal cell carcinoma cells. FEBS Lett. 2023;597(8):1098–113.PubMedCrossRef
32.
Bianchi C, Meregalli C, Bombelli S, Di Stefano V, Salerno F, Torsello B, et al. The glucose and lipid metabolism reprogramming is grade-dependent in clear cell renal cell carcinoma primary cultures and is targetable to modulate cell viability and proliferation. Oncotarget. 2017;8(69):113502–15.PubMedPubMedCentralCrossRef
33.
Ragone R, Sallustio F, Piccinonna S, Rutigliano M, Vanessa G, Palazzo S, et al. Renal cell carcinoma: a study through NMR-based metabolomics combined with transcriptomics. Diseases. 2016;4(1):7.PubMedPubMedCentralCrossRef
34.
Lucarelli G, Galleggiante V, Rutigliano M, Sanguedolce F, Cagiano S, Bufo P, et al. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma. Oncotarget. 2015;6(15):13371–86.PubMedPubMedCentralCrossRef
35.
Lucarelli G, Rutigliano M, Sallustio F, Ribatti D, Giglio A, Lepore Signorile M, et al. Integrated multi-omics characterization reveals a distinctive metabolic signature and the role of NDUFA4L2 in promoting angiogenesis, chemoresistance, and mitochondrial dysfunction in clear cell renal cell carcinoma. Aging (Albany NY). 2018;10(12):3957–85.PubMedCrossRef
36.
Bombelli S, Torsello B, De Marco S, Lucarelli G, Cifola I, Grasselli C, et al. 36-kDa annexin A3 isoform negatively modulates lipid storage in clear cell renal cell carcinoma cells. Am J Pathol. 2020;190(11):2317–26.PubMedCrossRef
37.
Lucarelli G, Rutigliano M, Loizzo D, di Meo NA, Lasorsa F, Mastropasqua M, et al. MUC1 tissue expression and its soluble form CA15-3 identify a clear cell renal cell carcinoma with distinct metabolic profile and poor clinical outcome. Int J Mol Sci. 2022;23(22):13968.PubMedPubMedCentralCrossRef
38.
Pathria G, Scott DA, Feng Y, Sang Lee J, Fujita Y, Zhang G, et al. Targeting the Warburg effect via LDHA inhibition engages ATF4 signaling for cancer cell survival. EMBO J. 2018;37(20):e99735.PubMedPubMedCentralCrossRef
39.
Li G, Li Y, Wang DY. Overexpression of miR-329-3p sensitizes osteosarcoma cells to cisplatin through suppression of glucose metabolism by targeting LDHA. Cell Biol Int. 2021;45(4):766–74.PubMedCrossRef
40.
Yu C, Hou L, Cui H, Zhang L, Tan X, Leng X, et al. LDHA upregulation independently predicts poor survival in lung adenocarcinoma, but not in lung squamous cell carcinoma. Fut Oncol. 2018;14(24):2483–92.CrossRef
41.
Ban EJ, Kim D, Kim JK, Kang SW, Lee J, Jeong JJ, et al. Lactate dehydrogenase A as a potential new biomarker for thyroid cancer. Endocrinol Metab (Seoul). 2021;36(1):96–105.PubMedCrossRef
42.
Huang X, Li X, Xie X, Ye F, Chen B, Song C, et al. High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer. Breast. 2016;30:39–46.PubMedCrossRef
43.
44.
45.
Cai H, Li J, Zhang Y, Liao Y, Zhu Y, Wang C, et al. LDHA promotes oral squamous cell carcinoma progression through facilitating glycolysis and epithelial-mesenchymal transition. Front Oncol. 2019;9:1446.PubMedPubMedCentralCrossRef
46.
Rathmell KW, Chen F, Creighton CJ. Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for pan-cancer studies. Oncoscience. 2015;2(2):81–90.PubMedPubMedCentralCrossRef
47.
Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD, Shen H, et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014;26(3):319–30.PubMedPubMedCentralCrossRef
48.
49.
Tamma R, Rutigliano M, Lucarelli G, Annese T, Ruggieri S, Cascardi E, et al. Microvascular density, macrophages, and mast cells in human clear cell renal carcinoma with and without bevacizumab treatment. Urol Oncol. 2019;37(6):355e11-359.CrossRef
50.
Netti GS, Lucarelli G, Spadaccino F, Castellano G, Gigante M, Divella C, et al. PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma. Aging (Albany NY). 2020;12(8):7585–602.PubMedCrossRef
51.
Lucarelli G, Rutigliano M, Ferro M, Giglio A, Intini A, Triggiano F, et al. Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma. Urol Oncol. 2017;35(7):461e15-527.CrossRef
52.
Lasorsa F, di Meo NA, Rutigliano M, Milella M, Ferro M, Pandolfo SD, et al. Immune checkpoint inhibitors in renal cell carcinoma: molecular basis and rationale for their use in clinical practice. Biomedicines. 2023;11(4):1071.PubMedPubMedCentralCrossRef
53.
Ghini V, Laera L, Fantechi B, Monte FD, Benelli M, McCartney A, et al. Metabolomics to assess response to immune checkpoint inhibitors in patients with non-small-cell lung cancer. Cancers (Basel). 2020;12(12):3574.PubMedCrossRef
54.
Lucarelli G, Netti GS, Rutigliano M, Lasorsa F, Loizzo D, Milella M, et al. MUC1 expression affects the immunoflogosis in renal cell carcinoma microenvironment through complement system activation and immune infiltrate modulation. Int J Mol Sci. 2023;24(5):4814.PubMedPubMedCentralCrossRef
55.
Lasorsa F, Rutigliano M, Milella M, Ferro M, Pandolfo SD, Crocetto F, et al. Cellular and molecular players in the tumor microenvironment of renal cell carcinoma. J Clin Med. 2023;12(12):3888.PubMedPubMedCentralCrossRef
56.
Luan Y, Zhang W, Xie J, Mao J. CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT/mTOR pathway. Clin Transl Oncol. 2021;23(2):222–8.PubMedCrossRef
57.
58.
Zhang XB, Shu WB, Li AB, Lan GH. The anion gap and mortality in critically ill patients with hip fractures. Contrast Media Mol Imaging. 2022;2022:1591507.PubMedPubMedCentral
59.
60.
Wei GH, Wang X. lncRNA MEG3 inhibit proliferation and metastasis of gastric cancer via p53 signaling pathway. Eur Rev Med Pharmacol Sci. 2017;21(17):3850–6.PubMed
61.
Yao Y, Liu C, Wang B, Guan X, Fang L, Zhan F, et al. HOXB9 blocks cell cycle progression to inhibit pancreatic cancer cell proliferation through the DNMT1/RBL2/c-Myc axis. Cancer Lett. 2022;533:215595.PubMedCrossRef
62.
Prendergast L, McClurg UL, Hristova R, Berlinguer-Palmini R, Greener S, Veitch K, et al. Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability. Nat Commun. 2020;11(1):4534.PubMedPubMedCentralCrossRef
63.
Shi K, Zhu X, Wu J, Chen Y, Zhang J, Sun X. Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma. Bioengineered. 2021;12(1):5950–70.PubMedPubMedCentralCrossRef
64.
St Paul M, Ohashi PS. The roles of CD8(+) T cell subsets in antitumor immunity. Trends Cell Biol. 2020;30(9):695–704.PubMedCrossRef
65.
Anderson NR, Minutolo NG, Gill S, Klichinsky M. Macrophage-based approaches for cancer immunotherapy. Cancer Res. 2021;81(5):1201–8.PubMedCrossRef
66.
Liang ML, Hsieh TH, Ng KH, Tsai YN, Tsai CF, Chao ME, et al. Downregulation of miR-137 and miR-6500-3p promotes cell proliferation in pediatric high-grade gliomas. Oncotarget. 2016;7(15):19723–37.PubMedPubMedCentralCrossRef
67.
Shao X, Zheng X, Ma D, Liu Y, Liu G. Inhibition of lncRNA-NEAT1 sensitizes 5-Fu resistant cervical cancer cells through de-repressing the microRNA-34a/LDHA axis. Biosci Rep. 2021;41(7):BSR20200533.PubMedPubMedCentralCrossRef
68.
Guo Z, Lu X, Yang F, Qin L, Yang N, Cai P, et al. The expression of miR-205 in prostate carcinoma and the relationship with prognosis in patients. Comput Math Methods Med. 2022;2022:1784791.PubMedPubMedCentralCrossRef
69.
Niu L, Wang XF, Wang XR. Crocin suppresses cell proliferation and migration by regulating miR-577/NFIB in renal cell carcinoma. J Biol Regul Homeost Agents. 2020;34(4):1523–7.PubMed
70.
Dong X, Fu X, Yu M, Li Z. Long intergenic non-protein coding RNA 1094 promotes initiation and progression of glioblastoma by promoting microRNA-577-regulated stabilization of brain-derived neurotrophic factor. Cancer Manag Res. 2020;12:5619–31.PubMedPubMedCentralCrossRef
Metadata
Title
CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma
Authors
Hui-feng Wu
Hao Liu
Zhe-wei Zhang
Ji-min Chen
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01449-0

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