Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5*rs34324334 and RAN*rs14035) with Susceptibility to Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Genomic DNA Extraction and Amplification Analysis
2.3. Bioinformatic Analysis
2.4. Statistical Analysis
3. Results
3.1. The Fundamental Characteristics of the Study Population
3.2. XPO5*rs34324334 and RAN*rs14035 Variants with Susceptibility to HCC
3.3. XPO5*rs34324334 and RAN*rs14035 Variants Stratified by Clinical and Laboratory Measurements among HCC Patients
3.4. In Silico Data Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Yang, C.; Huang, X.; Liu, Z.; Qin, W.; Wang, C. Metabolism-associated molecular classification of hepatocellular carcinoma. Mol. Oncol. 2020, 14, 896–913. [Google Scholar] [CrossRef] [Green Version]
- Llovet, J.M.; Kelley, R.K.; Villanueva, A.; Singal, A.G.; Pikarsky, E.; Roayaie, S.; Lencioni, R.; Koike, K.; Zucman-Rossi, J.; Finn, R.S. Hepatocellular carcinoma. Nat. Rev. Dis. Prim. 2021, 7, 6. [Google Scholar] [CrossRef] [PubMed]
- Saad, A.M.; Abdel-Megied, A.E.S.; Elbaz, R.A.; Hassab El-Nabi, S.E.; Elshazli, R.M. Genetic variants of APEX1 p.Asp148Glu and XRCC1 p.Gln399Arg with the susceptibility of hepatocellular carcinoma. J. Med. Virol. 2021, 93, 6278–6291. [Google Scholar] [CrossRef] [PubMed]
- Amer, T.; El-Baz, R.; Mokhtar, A.R.; El-Shaer, S.; Elshazli, R.; Settin, A. Genetic polymorphisms of IL-23R (rs7517847) and LEP (rs7799039) among Egyptian patients with hepatocellular carcinoma. Arch. Physiol. Biochem. 2017, 123, 279–285. [Google Scholar] [CrossRef]
- Lehman, E.M.; Soliman, A.S.; Ismail, K.; Hablas, A.; Seifeldin, I.A.; Ramadan, M.; El-Hamzawy, H.; Shoushtari, C.S.; Wilson, M.L. Patterns of hepatocellular carcinoma incidence in Egypt from a population-based cancer registry. Hepatol. Res. 2008, 38, 465–473. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ezzat, R.; Eltabbakh, M.; El Kassas, M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J. Gastrointest. Oncol. 2021, 13, 1919–1938. [Google Scholar] [CrossRef]
- Sagnelli, E.; Macera, M.; Russo, A.; Coppola, N.; Sagnelli, C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection 2020, 48, 7–17. [Google Scholar] [CrossRef] [PubMed]
- Margini, C.; Dufour, J.F. The story of HCC in NAFLD: From epidemiology, across pathogenesis, to prevention and treatment. Liver Int. 2016, 36, 317–324. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ni, J.S.; Zheng, H.; Huang, Z.P.; Hong, Y.G.; Ou, Y.L.; Tao, Y.P.; Wang, M.C.; Wang, Z.G.; Yang, Y.; Zhou, W.P. MicroRNA-197-3p acts as a prognostic marker and inhibits cell invasion in hepatocellular carcinoma. Oncol. Lett. 2019, 17, 2317–2327. [Google Scholar] [CrossRef] [Green Version]
- Chu, R.; Mo, G.; Duan, Z.; Huang, M.; Chang, J.; Li, X.; Liu, P. miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression. Cell Commun. Signal. 2014, 12, 45. [Google Scholar] [CrossRef]
- Sun, H.L.; Cui, R.; Zhou, J.; Teng, K.Y.; Hsiao, Y.H.; Nakanishi, K.; Fassan, M.; Luo, Z.; Shi, G.; Tili, E.; et al. ERK Activation Globally Downregulates miRNAs through Phosphorylating Exportin-5. Cancer Cell 2016, 30, 723–736. [Google Scholar] [CrossRef] [Green Version]
- Elshazli, R.M.; Toraih, E.A.; Hussein, M.H.; Ruiz, E.M.; Kandil, E.; Fawzy, M.S. Pan-Cancer Study on Variants of Canonical miRNA Biogenesis Pathway Components: A Pooled Analysis. Cancers 2023, 15, 338. [Google Scholar] [CrossRef]
- Oura, K.; Morishita, A.; Masaki, T. Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma—A Review. Int. J. Mol. Sci. 2020, 21, 8362. [Google Scholar] [CrossRef]
- Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281–297. [Google Scholar] [CrossRef] [Green Version]
- Carthew, R.W.; Sontheimer, E.J. Origins and Mechanisms of miRNAs and siRNAs. Cell 2009, 136, 642–655. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pasha, T.; Zatorska, A.; Sharipov, D.; Rogelj, B.; Hortobágyi, T.; Hirth, F. Karyopherin abnormalities in neurodegenerative proteinopathies. Brain 2021, 144, 2915–2932. [Google Scholar] [CrossRef]
- Quan, Y.; Ji, Z.-L.; Wang, X.; Tartakoff, A.M.; Tao, T. Evolutionary and Transcriptional Analysis of Karyopherin β Superfamily Proteins. Mol. Cell. Proteom. 2008, 7, 1254–1269. [Google Scholar] [CrossRef] [Green Version]
- Wu, K.; He, J.; Pu, W.; Peng, Y. The Role of Exportin-5 in MicroRNA Biogenesis and Cancer. Genom. Proteom. Bioinform. 2018, 16, 120–126. [Google Scholar] [CrossRef] [PubMed]
- Yi, R.; Qin, Y.; Macara, I.G.; Cullen, B.R. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes. Dev. 2003, 17, 3011–3016. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Matchett, K.B.; McFarlane, S.; Hamilton, S.E.; Eltuhamy, Y.S.; Davidson, M.A.; Murray, J.T.; Faheem, A.M.; El-Tanani, M. Ran GTPase in nuclear envelope formation and cancer metastasis. Adv. Exp. Med. Biol. 2014, 773, 323–351. [Google Scholar] [CrossRef] [Green Version]
- El-Tanani, M.; Dakirel, H.; Raynor, B.; Morgan, R. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy. Cancers 2016, 8, 35. [Google Scholar] [CrossRef] [Green Version]
- Krol, J.; Loedige, I.; Filipowicz, W. The widespread regulation of microRNA biogenesis, function and decay. Nat. Rev. Genet. 2010, 11, 597–610. [Google Scholar] [CrossRef]
- Bao, X.; Liu, H.; Liu, X.; Ruan, K.; Zhang, Y.; Zhang, Z.; Hu, Q.; Liu, Y.; Akram, S.; Zhang, J.; et al. Mitosis-specific acetylation tunes Ran effector binding for chromosome segregation. J. Mol. Cell Biol. 2018, 10, 18–32. [Google Scholar] [CrossRef]
- Sanz-García, M.; López-Sánchez, I.; Lazo, P.A. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol. Cell. Proteom. 2008, 7, 2199–2214. [Google Scholar] [CrossRef] [Green Version]
- Hayder, H.; O’Brien, J.; Nadeem, U.; Peng, C. MicroRNAs: Crucial regulators of placental development. Reproduction 2018, 155, R259–R271. [Google Scholar] [CrossRef] [Green Version]
- Zeng, Y.; Cullen, B.R. Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res. 2004, 32, 4776–4785. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Muqbil, I.; Bao, B.; Abou-Samra, A.B.; Mohammad, R.M.; Azmi, A.S. Nuclear export mediated regulation of microRNAs: Potential target for drug intervention. Curr. Drug. Targets 2013, 14, 1094–1100. [Google Scholar] [CrossRef] [Green Version]
- Lee, E.J.; Baek, M.; Gusev, Y.; Brackett, D.J.; Nuovo, G.J.; Schmittgen, T.D. Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA 2008, 14, 35–42. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, D.; Fu, Z.; Yang, G.; Gao, D.; Wang, T.; Liu, Z.; Li, G.; Wang, Y. Exportin-5 SUMOylation promotes hepatocellular carcinoma progression. Exp. Cell Res. 2020, 395, 112219. [Google Scholar] [CrossRef]
- Melo, S.A.; Moutinho, C.; Ropero, S.; Calin, G.A.; Rossi, S.; Spizzo, R.; Fernandez, A.F.; Davalos, V.; Villanueva, A.; Montoya, G.; et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell 2010, 18, 303–315. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Melo, S.A.; Esteller, M. A precursor microRNA in a cancer cell nucleus: Get me out of here! Cell Cycle 2011, 10, 922–925. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Y.C.; Song, C.H.; Yang, W.J.; Dai, L.P.; Wang, P.; Shi, J.X.; Zhang, J.Y.; Wang, K.J. [Correlation between tag single nucleotide polymorphisms of microRNA regulatory genes and the genetic susceptibility of primary liver cancer]. Zhonghua Yu Fang Yi Xue Za Zhi 2012, 46, 533–537. [Google Scholar]
- Gomaa, A.; Allam, N.; Elsharkawy, A.; El Kassas, M.; Waked, I. Hepatitis C infection in Egypt: Prevalence, impact and management strategies. Hepat. Med. 2017, 9, 17–25. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef]
- Marrero, J.A.; Kulik, L.M.; Sirlin, C.B.; Zhu, A.X.; Finn, R.S.; Abecassis, M.M.; Roberts, L.R.; Heimbach, J.K. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018, 68, 723–750. [Google Scholar] [CrossRef] [Green Version]
- Botstein, D.; White, R.L.; Skolnick, M.; Davis, R.W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 1980, 32, 314–331. [Google Scholar]
- Galal, A.A.; Abd Elmajeed, A.A.; Elbaz, R.A.; Wafa, A.M.; Elshazli, R.M. Association of Apolipoprotein E gene polymorphism with the risk of T2DM and obesity among Egyptian subjects. Gene 2021, 769, 145223. [Google Scholar] [CrossRef]
- Elsaid, A.; Elshazli, R.; El-Tarapely, F.; Darwish, H.; Abdel-Malak, C. Association of monoallelic MUTYH mutation among Egyptian patients with colorectal cancer. Fam. Cancer 2017, 16, 83–90. [Google Scholar] [CrossRef]
- Yahia, S.; Hammad, A.; El-Gilany, A.H.; El-Assmy, M.; El-Tanbouly, R.; Elsaid, A.M.; Elmoursi, L.Z.; Elshazli, R.M.; Shoaib, R.M. Genetic variant in the 5′ untranslated region of endothelin1 (EDN1) gene in children with primary nephrotic syndrome. J. Biochem. Mol. Toxicol. 2022, 36, e22963. [Google Scholar] [CrossRef]
- Alghamdi, S.A.; Kattan, S.W.; Toraih, E.A.; Alrowaili, M.G.; Fawzy, M.S.; Elshazli, R.M. Association of AIRE (rs2075876), but not CTLA4 (rs231775) polymorphisms with systemic lupus erythematosus. Gene 2021, 768, 145270. [Google Scholar] [CrossRef] [PubMed]
- Pajares, M.J.; Alemany-Cosme, E.; Goñi, S.; Bandres, E.; Palanca-Ballester, C.; Sandoval, J. Epigenetic Regulation of microRNAs in Cancer: Shortening the Distance from Bench to Bedside. Int. J. Mol. Sci. 2021, 22, 7350. [Google Scholar] [CrossRef] [PubMed]
- Cai, X.; Hagedorn, C.H.; Cullen, B.R. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004, 10, 1957–1966. [Google Scholar] [CrossRef] [Green Version]
- Deng, Y.; Wang, C.C.; Choy, K.W.; Du, Q.; Chen, J.; Wang, Q.; Li, L.; Chung, T.K.H.; Tang, T. Therapeutic potentials of gene silencing by RNA interference: Principles, challenges, and new strategies. Gene 2014, 538, 217–227. [Google Scholar] [CrossRef]
- Fawzy, M.S.; Abu AlSel, B.T.; Toraih, E.A. Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end-stage renal disease. J. Clin. Lab. Anal. 2020, 34, e23520. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.N.; Kim, J.O.; Lee, S.M.; Park, H.; Lee, J.H.; Rim, K.S.; Hwang, S.G.; Kim, N.K. Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma. PLoS ONE 2016, 11, e0162279. [Google Scholar] [CrossRef]
- Leaderer, D.; Hoffman, A.E.; Zheng, T.; Fu, A.; Weidhaas, J.; Paranjape, T.; Zhu, Y. Genetic and epigenetic association studies suggest a role of microRNA biogenesis gene exportin-5 (XPO5) in breast tumorigenesis. Int. J. Mol. Epidemiol. Genet. 2011, 2, 9–18. [Google Scholar] [PubMed]
- Lund, E.; Güttinger, S.; Calado, A.; Dahlberg, J.E.; Kutay, U. Nuclear export of microRNA precursors. Science 2004, 303, 95–98. [Google Scholar] [CrossRef] [Green Version]
- Cho, S.H.; Ko, J.J.; Kim, J.O.; Jeon, Y.J.; Yoo, J.K.; Oh, J.; Oh, D.; Kim, J.W.; Kim, N.K. 3′-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population. PLoS ONE 2015, 10, e0131125. [Google Scholar] [CrossRef] [Green Version]
- Shao, Y.; Shen, Y.; Zhao, L.; Guo, X.; Niu, C.; Liu, F. Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis. J. Cancer 2020, 11, 2181–2191. [Google Scholar] [CrossRef]
- Song, K.; Yi, J.; Shen, X.; Cai, Y. Genetic polymorphisms of glutathione S-transferase genes GSTM1, GSTT1 and risk of hepatocellular carcinoma. PLoS ONE 2012, 7, e48924. [Google Scholar] [CrossRef]
- Gholami, M.; Larijani, B.; Sharifi, F.; Hasani-Ranjbar, S.; Taslimi, R.; Bastami, M.; Atlasi, R.; Amoli, M.M. MicroRNA-binding site polymorphisms and risk of colorectal cancer: A systematic review and meta-analysis. Cancer Med. 2019, 8, 7477–7499. [Google Scholar] [CrossRef] [PubMed]
- Horikawa, Y.; Wood, C.G.; Yang, H.; Zhao, H.; Ye, Y.; Gu, J.; Lin, J.; Habuchi, T.; Wu, X. Single Nucleotide Polymorphisms of microRNA Machinery Genes Modify the Risk of Renal Cell Carcinoma. Clin. Cancer Res. 2008, 14, 7956–7962. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Osuch-Wojcikiewicz, E.; Bruzgielewicz, A.; Niemczyk, K.; Sieniawska-Buccella, O.; Nowak, A.; Walczak, A.; Majsterek, I. Association of Polymorphic Variants of miRNA Processing Genes with Larynx Cancer Risk in a Polish Population. BioMed. Res. Int. 2015, 2015, 298378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Y.; Zhang, F.; Xing, C. A Systematic Review and Meta-Analysis for the Association of Gene Polymorphisms in RAN with Cancer Risk. Dis. Markers 2020, 2020, 9026707. [Google Scholar] [CrossRef]
- Wang, C.; Dong, H.; Fan, H.; Wu, J.; Wang, G. Genetic polymorphisms of microRNA machinery genes predict overall survival of esophageal squamous carcinoma. J. Clin. Lab. Anal. 2018, 32, e22170. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Q.; Li, X.; Li, Y.; Chen, S.; Shen, X.; Dong, X.; Song, Y.; Zhang, X.; Huang, K. Expression of the PTEN/FOXO3a/PLZF signalling pathway in pancreatic cancer and its significance in tumourigenesis and progression. Investig. New Drugs 2020, 38, 321–328. [Google Scholar] [CrossRef] [PubMed]
- Cao, J.; Zhu, S.; Zhou, W.; Li, J.; Liu, C.; Xuan, H.; Yan, J.; Zheng, L.; Zhou, L.; Yu, J.; et al. PLZF mediates the PTEN/AKT/FOXO3a signaling in suppression of prostate tumorigenesis. PLoS ONE 2013, 8, e77922. [Google Scholar] [CrossRef] [Green Version]
- Shen, H.; Zhan, M.; Zhang, Y.; Huang, S.; Xu, S.; Huang, X.; He, M.; Yao, Y.; Man, M.; Wang, J. PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2. Cell Death Dis. 2018, 9, 71. [Google Scholar] [CrossRef] [Green Version]
- Qin, Y.; Yu, J.; Zhang, M.; Qin, F.; Lan, X. ZEB1 promotes tumorigenesis and metastasis in hepatocellular carcinoma by regulating the expression of vimentin. Mol. Med. Rep. 2019, 19, 2297–2306. [Google Scholar] [CrossRef] [Green Version]
Variable | Levels | Cancer-Free Controls | HCC Patients | p-Value |
---|---|---|---|---|
(n = 127) | (n = 107) | |||
Demographic and Clinical Characteristics | ||||
Age, years | Median (IQR) | 54.0 (49.0–58.0) | 53.0 (45.0–61.0) | 0.832 |
≤40 years | 15 (11.8) | 21 (19.6) | 0.106 | |
>40 years | 112 (88.2) | 86 (80.4) | ||
Weight, kg | Median (IQR) | 80.0 (76.0–87.0) | 84.0 (78.0–89.0) | 0.014 |
Gender | Males | 94 (74.0) | 87 (81.3) | 0.211 |
Females | 33 (26.0) | 20 (18.7) | ||
Smoking | Positive | 17 (13.4) | 32 (29.9) | 0.002 |
Negative | 110 (86.6) | 75 (70.1) | ||
Consanguinity | Positive | --- | 26 (24.3) | NA |
Negative | --- | 81 (75.7) | ||
Cirrhotic liver | Positive | --- | 79 (73.8) | NA |
Negative | --- | 28 (26.2) | ||
Hypertension | Positive | --- | 33 (30.8) | NA |
Negative | --- | 74 (69.2) | ||
Ascites status | Presence | --- | 72 (67.3) | NA |
Absence | --- | 35 (32.7) | ||
Ascites grade | Grade 1 (Mild) | --- | 7 (6.5) | NA |
Grade 2 (Moderate) | --- | 18 (16.8) | ||
Grade 3 (Large) | --- | 47 (43.9) | ||
Splenomegaly | Presence | --- | 93 (86.9) | NA |
Absence | --- | 14 (13.1) | ||
Splenomegaly classes | Mild enlarged | --- | 40 (37.4) | NA |
Moderate enlarged | --- | 44 (41.1) | ||
Massive enlarged | --- | 9 (8.4) | ||
Biochemical Measurements | ||||
ALT, U/L | Median (IQR) | 29.0 (21.0–35.0) | 52.0 (33.0–85.0) | <0.001 |
AST, U/L | Median (IQR) | 26.0 (21.0–31.0) | 64.0 (42.0–115.0) | <0.001 |
Albumin, g/L | Median (IQR) | 42.0 (38.0–47.0) | 31.0 (27.0–36.0) | <0.001 |
Total bilirubin, mg/dL | Median (IQR) | 0.90 (0.70–1.00) | 1.60 (1.10–3.50) | <0.001 |
Direct bilirubin, mg/dL | Median (IQR) | 0.21 (0.15–0.26) | 0.84 (0.47–2.12) | <0.001 |
Indirect bilirubin, mg/dL | Median (IQR) | 0.67 (0.51–0.84) | 0.81 (0.56–1.30) | <0.001 |
INR | Median (IQR) | 1.00 (1.00–1.10) | 1.20 (1.10–1.40) | <0.001 |
Creatinine, mg/dL | Median (IQR) | 0.90 (0.70–1.00) | 1.00 (0.80–1.30) | <0.001 |
Serological Investigations and Tumor Markers | ||||
Anti-HCV | Positive | 0.0 (0.0 | 87 (81.3) | <0.001 |
Negative | 127 (100.0) | 20 (18.7) | ||
AFP, ng/mL | Median (IQR) | 7.0 (4.0–9.4) | 115.0 (32.0–582.0) | <0.001 |
Hematological Parameters | ||||
WBCs, ×109/L | Median (IQR) | 7.8 (5.8–9.4) | 5.3 (3.9–8.5) | <0.001 |
RBCs, ×1012/L | Median (IQR) | 4.5 (4.1–5.0) | 3.7 (3.1–4.3) | <0.001 |
Hematocrit (HCT), % | Median (IQR) | 37.5 (34.1–42.0) | 34.9 (30.2–39.9) | <0.001 |
Hemoglobin, g/dL | Median (IQR) | 13.5 (12.8–15.0) | 12.0 (10.5–13.6) | <0.001 |
Platelet count, ×109/L | Median (IQR) | 258.0 (198.0–341.0) | 127.0 (92.0–164.0) | <0.001 |
Genetic Polymorphisms | Cancer-Free Controls | HCC Patients | OR (95% CI) | p-Value |
---|---|---|---|---|
XPO5 (rs34324334; c.722G>A) | ||||
Genotypic frequencies | n (%) 127 | n (%) 107 | ||
G/G | 101 (79.5) | 30 (28.0) | 1.0 | |
G/A | 22 (17.3) | 31 (29.0) | 4.75 (2.40–9.38) | <0.001 |
A/A | 4 (3.2) | 46 (43.0) | 38.7 (12.9–116.3) | <0.001 |
HWE | χ2 = 3.40, p = 0.058 | χ2 = 17.75, p < 0.001 | ||
Allelic frequencies | n (%) 254 | n (%) 214 | ||
G allele | 224 (88.2) | 91 (42.5) | 1.0 | <0.001 |
A allele | 30 (11.8) | 123 (57.5) | 10.09 (6.32–16.11) | |
RAN (rs14035; c.*770C>T) | ||||
Genotypic frequencies | n (%) 127 | n (%) 107 | ||
C/C | 46 (36.2) | 35 (32.7) | 1.0 | |
C/T | 54 (42.5) | 23 (21.5) | 0.56 (0.29–1.08) | 0.099 |
T/T | 27 (21.3) | 49 (45.8) | 2.38 (1.25–4.54) | 0.010 |
HWE | χ2 = 2.15, p = 0.142 | χ2 = 33.9, p < 0.001 | ||
Allelic frequencies | n (%) 254 | n (%) 214 | ||
C allele | 146 (57.5) | 93 (43.5) | 1.0 | 0.003 |
T allele | 108 (42.5) | 121 (56.5) | 1.76 (1.22–2.54) |
Model | Genotypes | Cancer-Free Controls | HCC Patients | Crude OR (95% CI) | p-Value | Adjusted OR (95% CI) | p-Value |
---|---|---|---|---|---|---|---|
XPO5*rs34324334 | n (%) 127 | n (%) 107 | |||||
Codominant | G/G | 101 (79.5) | 30 (28.0) | 1.0 | <0.001 | 1.0 | <0.001 |
G/A | 22 (17.3) | 31 (29.0) | 4.74 (2.40–9.38) | 4.73 (2.38–9.39) | |||
A/A | 4 (3.2) | 46 (43.0) | 38.7 (12.9–116.3) | 39.9 (13.2–121.1) | |||
Dominant | G/G | 101 (79.5) | 30 (28.0) | 1.0 | <0.001 | 1.0 | <0.001 |
G/A + A/A | 26 (20.5) | 77 (72.0) | 9.97 (5.45–18.22) | 10.1 (5.46–18.4) | |||
Recessive | G/G + G/A | 123 (96.8) | 61 (57.0) | 1.0 | <0.001 | 1.0 | <0.001 |
A/A | 4 (3.2) | 46 (43.0) | 23.2 (7.98–67.4) | 24.1 (8.23–70.8) | |||
Log-additive | --- | --- | --- | 5.68 (3.61–8.94) | <0.001 | 5.73 (3.63–9.05) | <0.001 |
RAN/rs14035 | n (%) 127 | n (%) 107 | |||||
Codominant | C/C | 46 (36.2) | 35 (32.7) | 1.0 | <0.001 | 1.0 | <0.001 |
C/T | 54 (42.5) | 23 (21.5) | 0.56 (0.29–1.08) | 0.53 (0.27–1.03) | |||
T/T | 27 (21.3) | 49 (45.8) | 2.39 (1.25–4.54) | 2.44 (1.27–4.68) | |||
Dominant | C/C | 46 (36.2) | 35 (32.7) | 1.0 | 0.570 | 1.0 | 0.610 |
C/T + T/T | 81 (63.8) | 72 (67.3) | 1.17 (0.68–2.01) | 1.15 (0.67–1.99) | |||
Recessive | C/C + C/T | 100 (78.7) | 58 (54.2) | 1.0 | <0.001 | 1.0 | <0.001 |
T/T | 27 (21.3) | 49 (45.8) | 3.13 (1.77–5.53) | 3.27 (1.83–5.83) | |||
Log-additive | --- | --- | --- | 1.53 (1.11–2.11) | 0.009 | 1.54 (1.11–2.13) | 0.008 |
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Elsalahaty, M.I.; Salama, A.F.; Diab, T.; Ghazy, M.; Toraih, E.; Elshazli, R.M. Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5*rs34324334 and RAN*rs14035) with Susceptibility to Hepatocellular Carcinoma. J. Pers. Med. 2023, 13, 959. https://doi.org/10.3390/jpm13060959
Elsalahaty MI, Salama AF, Diab T, Ghazy M, Toraih E, Elshazli RM. Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5*rs34324334 and RAN*rs14035) with Susceptibility to Hepatocellular Carcinoma. Journal of Personalized Medicine. 2023; 13(6):959. https://doi.org/10.3390/jpm13060959
Chicago/Turabian StyleElsalahaty, Mohamed I., Afrah F. Salama, Thoria Diab, Medhat Ghazy, Eman Toraih, and Rami M. Elshazli. 2023. "Unleash Multifunctional Role of miRNA Biogenesis Gene Variants (XPO5*rs34324334 and RAN*rs14035) with Susceptibility to Hepatocellular Carcinoma" Journal of Personalized Medicine 13, no. 6: 959. https://doi.org/10.3390/jpm13060959