Abstract
Phosphofructokinase muscle (PFKM), encoded by PFKM on chromosome 12q13.11, is abundantly expressed in skeletal muscle. PFKM is a member of the glycolytic gene family that is involved in the carcinogenesis of various tumours; however, its potential role in the development of epithelial ovarian cancer in Han Chinese women remains unclear. In China, the Han population comprises a large representative group. Therefore, this study aimed to explore the relationship between PFKM polymorphisms and susceptibility to ovarian cancer. We examined 275 patients with epithelial ovarian cancer and 371 healthy individuals. The polymerase chain reaction restriction fragment length polymorphism method was used to genotype two single nucleotide polymorphisms in PFKM, including rs4075913 and rs2228500. The results showed that rs2228500 did not affect the susceptibility to ovarian cancer, but for rs4075913, the frequency of the AG/GG genotypes and G allele in ovarian cancer patients was significantly higher than that in healthy individuals. In addition, patients with the AG/GG genotypes had a worse prognosis than did patients with the AA genotype (P value = 0.0327). Therefore, PFKM is likely related to the susceptibility and prognosis of epithelial ovarian cancer in the Chinese Han population, and rs4075913 is a potential risk factor.
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References
Ahsan H, Halpern J, Kibriya MG et al (2014) A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age. Cancer Epidemiology, Biomarkers & Prevention: a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 23(4):658–669. https://doi.org/10.1158/1055-9965.EPI-13-0340
Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
Chandra A, Pius C, Nabeel M et al (2019) Ovarian cancer: current status and strategies for improving therapeutic outcomes. Cancer Med 8(16):7018–7031. https://doi.org/10.1002/cam4.2560
Chang HW, Yang CH, Chang PL, Cheng YH, Chuang LY (2006) SNP-RFLPing: restriction enzyme mining for SNPs in genomes. BMC Genomics 7:30. https://doi.org/10.1186/1471-2164-7-30
Chen Y, Yu Q, Duan X et al (2020) Phosphofructokinase-M inhibits cell growth via modulating the FOXO3 pathway in renal cell carcinoma cells. Biochem Biophys Res Commun 530(1):67–74. https://doi.org/10.1016/j.bbrc.2020.06.062
Coughlan AY, Testa G (2021) Exploiting epigenetic dependencies in ovarian cancer therapy. Int J Cancer 149(10):1732–1743. https://doi.org/10.1002/ijc.33727
Epstein T, Gatenby RA, Brown JS (2017) The Warburg effect as an adaptation of cancer cells to rapid fluctuations in energy demand. PLoS ONE 12(9):e0185085. https://doi.org/10.1371/journal.pone.0185085
Foulkes WD (2021) The ten genes for breast (and ovarian) cancer susceptibility. Nat Rev Clin Oncol 18(5):259–260. https://doi.org/10.1038/s41571-021-00491-3
Gao C, Zhuang J, Zhou C et al (2019) SNP mutation-related genes in breast cancer for monitoring and prognosis of patients: A study based on the TCGA database. Cancer Med 8(5):2303–2312. https://doi.org/10.1002/cam4.2065
Gao W, Huang M, Chen X et al (2021) The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells. Cell Death Dis 12(4):408. https://doi.org/10.1038/s41419-021-03681-0
Gupta KK, Gupta VK, Naumann RW (2019) Ovarian cancer: screening and future directions. Int J Gynecol Cancer: off J Int Gynecol Cancer Soc 29(1):195–200. https://doi.org/10.1136/ijgc-2018-000016
Hannibal CG, Frederiksen K, Vang R, Kurman RJ, Kjaer SK (2020) Risk of specific types of ovarian cancer after borderline ovarian tumors in Denmark: A nationwide study. Int J Cancer 147(4):990–995. https://doi.org/10.1002/ijc.32864
Howard TD, Akots G, Bowden DW (1996) Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): reassignment to human chromosome 12q. Genomics 34(1):122–127. https://doi.org/10.1006/geno.1996.0250
Keildson S, Fadista J, Ladenvall C et al (2014) Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity. Diabetes 63(3):1154–1165. https://doi.org/10.2337/db13-1301
Lee SY, Jin CC, Choi JE et al (2016) Genetic polymorphisms in glycolytic pathway are associated with the prognosis of patients with early stage non-small cell lung cancer. Sci Rep 6:35603. https://doi.org/10.1038/srep35603
Menon U, Karpinskyj C, Gentry-Maharaj A (2018) Ovarian cancer prevention and screening. Obstet Gynecol 131(5):909–927. https://doi.org/10.1097/AOG.0000000000002580
Shi L, Pan H, Liu Z, Xie J, Han W (2017) Roles of PFKFB3 in cancer. Signal Transduct Target Ther 2:17044. https://doi.org/10.1038/sigtrans.2017.44
Silwal-Pandit L, Langerød A, Børresen-Dale AL (2017) TP53 Mutations in Breast and Ovarian Cancer. Cold Spring Harb Perspect Med 7(1):a026252. https://doi.org/10.1101/cshperspect.a026252
Solé X, Guinó E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies. Bioinformatics (oxford, England) 22(15):1928–1929. https://doi.org/10.1093/bioinformatics/btl268
Sun CM, Xiong DB, Yan Y et al (2016) Genetic alteration in phosphofructokinase family promotes growth of muscle-invasive bladder cancer. Int J Biol Markers 31(3):e286–e293. https://doi.org/10.5301/jbm.5000189
Tan D, Sheng L, Yi QH (2018) Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer. Cancer Biomark: Sect A Disease Mark 21(2):287–297. https://doi.org/10.3233/CBM-170357
Teoh, S. T., & Lunt, S. Y. (2018). Metabolism in cancer metastasis: bioenergetics, biosynthesis, and beyond. Wiley interdisciplinary reviews. Systems biology and medicine, 10(2), https://doi.org/10.1002/wsbm.1406. https://doi.org/10.1002/wsbm.1406.
Thomas LW, Ashcroft M (2019) Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria. Cellular Mol Life Sci: CMLS 76(9):1759–1777. https://doi.org/10.1007/s00018-019-03039-y
Torre LA, Trabert B, DeSantis CE et al (2018) Ovarian cancer statistics, 2018. CA: Cancer J Clin 68(4):284–296. https://doi.org/10.3322/caac.21456
Vieux EF, Kwok PY, Miller RD (2002) Primer design for PCR and sequencing in high-throughput analysis of SNPs. BioTechniques Suppl, 28–32
Webb PM, Jordan SJ (2017) Epidemiology of epithelial ovarian cancer. best practice & research. Clin Obst Gynaecol 41:3–14. https://doi.org/10.1016/j.bpobgyn.2016.08.006
Webb BA, Forouhar F, Szu FE et al (2015) Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations. Nature 523(7558):111–114. https://doi.org/10.1038/nature14405
Wei JH, Feng ZH, Cao Y et al (2019) Predictive value of single-nucleotide polymorphism signature for recurrence in localised renal cell carcinoma: a retrospective analysis and multicentre validation study. Lancet Oncol 20(4):591–600. https://doi.org/10.1016/S1470-2045(18)30932-X
Xintaropoulou C, Ward C, Wise A et al (2018) Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment. BMC Cancer 18(1):636. https://doi.org/10.1186/s12885-018-4521-4
Yang C, Xia BR, Zhang ZC et al (2020) Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant. Front Immunol 11:577869. https://doi.org/10.3389/fimmu.2020.577869
Yi, W., Clark, P. M., Mason, D. E., et al. (2012). Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science (New York, N.Y.), 337(6097), 975–980. DOI: https://doi.org/10.1126/science.1222278.
Zhang Z, Deng X, Liu Y et al (2019) PKM2, function and expression and regulation. Cell Biosci 9:52. https://doi.org/10.1186/s13578-019-0317-8
Zhang HB, Zeng Y, Li TL, Wang G (2020) Correlation between polymorphisms in IGF2/H19 gene locus and epithelial ovarian cancer risk in Chinese population. Genomics 112(3):2510–2515. https://doi.org/10.1016/j.ygeno.2020.02.002
Zhou Y, Lin F, Wan T et al (2021) ZEB1 enhances Warburg effect to facilitate tumorigenesis and metastasis of HCC by transcriptionally activating PFKM. Theranostics 11(12):5926–5938. https://doi.org/10.7150/thno.56490
Acknowledgements
Thanks to Dr. Linjie Zhao and Dr. Zhilong Li for helping to polish this paper.
Funding
This work was supported by the National Natural Science Foundation of China (No. 81974226, No. 81974365 and No. 32171264) and Sichuan Science and Technology Program (No. 2020ZYD007 and No. 2021YFS0026).
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(I) Conception and design: Qinni Yang;(II) Administrative support: Lin Zhang;(III) Provision of study materials or patients: Bin Zhou; Lin Zhang;(IV) Collection and assembly of data: Qinni Yang; Ran Zhang; Min Su; Siyu Long(V) Data analysis and interpretation: Qinni Yang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
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Yang, Q., Zhang, R., Long, S. et al. Prognostic Value of PFKM Polymorphisms and Susceptibility to Epithelial Ovarian Cancer in Han Women of Southwest China. Iran J Sci Technol Trans Sci 46, 1275–1282 (2022). https://doi.org/10.1007/s40995-022-01328-z
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DOI: https://doi.org/10.1007/s40995-022-01328-z