Genetic Variants of lncRNA MALAT1 Exert Diverse Impacts on the Risk and Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Subjects, Ethics, and Consent
2.2. Genomic DNA Extraction
2.3. Selection of MALAT1 SNPs
2.4. Genotyping of MALAT1 SNPs
2.5. Bioinformatics Analysis
2.6. Statistical Analysis
3. Results
3.1. Demographic Characteristics of Recruited Subjects
3.2. Associations between MALAT1 Candidate SNPs and HCC Susceptibility
3.3. Relationships between Clinicopathological Features of HCC and MALAT1 SNPs in Different Genders
3.4. Relationships between Clinicopathological Features and MALAT1 SNPs in HCC Patients Who Smoked Tobacco
3.5. Serum Alpha-Fetoprotein (AFP), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) Levels among Different MALAT1 SNP Carriers in HCC Patients
3.6. Clinical Relevance of MALAT1 Expression Levels in HCC Patients with or without Hepatitis Infection
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Controls (N = 1199) n (%) | Patients (N = 394) n (%) | p Value |
---|---|---|---|
Age (years) | |||
≥55 | 912 (76.1%) | 307 (77.9%) | 0.451 |
Gender | |||
Male | 839 (70%) | 273 (69.3%) | 0.797 |
Cigarette smoking | |||
Yes | 471 (39.3%) | 156 (39.6%) | 0.913 |
Alcohol consumption | |||
Yes | 169 (14.1%) | 139 (35.3%) | <0.001 * |
HBsAg | |||
Positive | 146 (12.2%) | 167 (42.4%) | <0.001 * |
Anti-HCV | |||
Positive | 53 (4.4%) | 178 (45.2%) | <0.001 * |
AFP (ng/mL) a | 20.83 | ||
AST (IU/L) a | 48 | ||
ALT (IU/L) a | 43 | ||
Stage | |||
III + IV | 117 (29.7%) | ||
Tumor T status | |||
T3 + T4 | 112 (28.4%) | ||
Lymph node status | |||
N1 + N2 + N3 | 12 (3%) | ||
Metastasis | |||
M1 | 19 (4.8%) | ||
Child–Pugh grade | |||
B or C | 74 (18.8%) | ||
Liver cirrhosis | |||
Positive | 326 (82.7%) |
Variable | Controls (N = 1199) n (%) | Patients (N = 394) n (%) | OR (95% CI) | AOR (95% CI) a |
---|---|---|---|---|
rs3200401 | ||||
CC | 802 (66.9%) | 263 (66.8%) | 1.000 (reference) | 1.000 (reference) |
CT | 347 (28.9%) | 117 (29.7%) | 1.028 (0.799–1.322) | 1.051 (0.805–1.372) |
TT | 50 (4.2%) | 14 (3.6%) | 0.854 (0.465–1.570) | 0.881 (0.459–1.689) |
CT + TT | 397 (33.1%) | 131 (33.2%) | 1.006 (0.790–1.281) | 1.030 (0.797–1.331) |
rs619586 | ||||
AA | 1014 (84.6%) | 330 (83.8%) | 1.000 (reference) | 1.000 (reference) |
AG | 175 (14.6%) | 61 (15.5%) | 1.071 (0.780–1.470) | 0.982 (0.701–1.376) |
GG | 10 (0.8%) | 3 (0.8%) | 0.922 (0.252–3.370) | 0.563 (0.141–2.250) |
AG + GG | 185 (15.4%) | 64 (16.2%) | 1.063 (0.780–1.450) | 0.954 (0.686–1.327) |
rs1194338 | ||||
CC | 510 (42.5%) | 172 (43.7%) | 1.000 (reference) | 1.000 (reference) |
CA | 537 (44.8%) | 175 (44.4%) | 0.966 (0.758–1.232) | 0.980 (0.759–1.266) |
AA | 152 (12.7%) | 47 (11.9%) | 0.917 (0.633–1.327) | 0.995 (0.672–1.474) |
CA + AA | 689 (57.5%) | 222 (56.3%) | 0.955 (0.759–1.202) | 0.983 (0.772–1.253) |
Variable | Controls (N = 287) n (%) | Patients (N = 87) n (%) | OR (95% CI) | AOR (95% CI) a |
---|---|---|---|---|
rs3200401 | ||||
CC | 193 (67.2%) | 55 (63.2%) | 1.000 (reference) | 1.000 (reference) |
CT | 82 (28.6%) | 30 (34.5%) | 1.284 (0.768–2.147) | 1.452 (0.837–2.516) |
TT | 12 (4.2%) | 2 (2.3%) | 0.585 (0.127–2.692) | 0.725 (0.148–3.548) |
CT + TT | 94 (32.8%) | 32 (36.8%) | 1.195 (0.724–1.971) | 1.364 (0.799–2.330) |
rs619586 | ||||
AA | 239 (83.3%) | 82 (94.3%) | 1.000 (reference) | 1.000 (reference) |
AG | 47 (16.4%) | 5 (5.7%) | 0.310 (0.119–0.806) p = 0.016 * | 0.289 (0.108–0.773) p = 0.013 * |
GG | 1 (0.3%) | 0 (0%) | NA | NA |
AG + GG | 48 (16.7%) | 5 (5.7%) | 0.304 (0.117–0.789) p = 0.014 * | 0.286 (0.107–0.765) p = 0.013 * |
rs1194338 | ||||
CC | 124 (43.2%) | 36 (41.4%) | 1.000 (reference) | 1.000 (reference) |
CA | 126 (43.9%) | 42 (48.3%) | 1.148 (0.690–1.911) | 1.313 (0.760–2.266) |
AA | 37 (12.9%) | 9 (10.3%) | 0.838 (0.370–1.898) | 1.330 (0.548–3.232) |
CA + AA | 163 (56.8%) | 51 (58.6%) | 1.078 (0.663–1.753) | 1.316 (0.778–2.224) |
Variable | Genotypic Frequencies | |||
---|---|---|---|---|
CC (%) (n = 51) | CA + AA (%) (n = 70) | OR (95% CI) | p Value | |
Clinical Stage | ||||
Stage III/IV | 12 (23.5%) | 21 (30%) | 1.393 (0.611–3.177) | 0.431 |
Tumor size | ||||
>T2 | 9 (17.6%) | 20 (28.6%) | 1.867 (0.769–4.533) | 0.168 |
Lymph node metastasis | ||||
Yes | 2 (3.9%) | 0 (0%) | NA | NA |
Distant metastasis | ||||
Yes | 3 (5.9%) | 2 (2.9%) | 0.471 (0.076–2.925) | 0.419 |
Vascular invasion | ||||
Yes | 13 (25.5%) | 8 (11.4%) | 0.377 (0.143–0.994) | 0.049 * |
Child–Pugh grade | ||||
B or C | 12 (23.5%) | 13 (18.6%) | 0.741 (0.306–1.794) | 0.507 |
HBsAg | ||||
Positive | 16 (31.4%) | 22 (31.4%) | 1.003 (0.461–2.182) | 0.995 |
Anti-HCV | ||||
Positive | 28 (54.9%) | 39 (55.7%) | 1.033 (0.500–2.135) | 0.929 |
Liver cirrhosis | ||||
Positive | 45 (88.2%) | 58 (82.9%) | 0.644 (0.225–1.850) | 0.414 |
Variable | Genotypic Frequencies | |||
---|---|---|---|---|
CC (%) (n = 64) | CA + AA (%) (n = 92) | OR (95% CI) | p Value | |
Clinical stage | ||||
Stage III/IV | 23 (35.9%) | 26 (28.3%) | 0.702 (0.355–1.39) | 0.311 |
Tumor size | ||||
>T2 | 23 (35.9%) | 26 (28.3%) | 0.702 (0.355–1.39) | 0.311 |
Lymph node metastasis | ||||
Yes | 2 (3.1%) | 3 (3.3%) | 1.045 (0.170–6.439) | 0.962 |
Distant metastasis | ||||
Yes | 2 (3.1%) | 5 (5.4%) | 1.782 (0.335–9.482) | 0.498 |
Vascular invasion | ||||
Yes | 14 (21.9%) | 11 (12%) | 0.485 (0.204–1.152) | 0.101 |
Child–Pugh grade | ||||
B or C | 17 (26.6%) | 12 (13%) | 0.415 (0.182–0.944) | 0.036 * |
HBsAg | ||||
Positive | 28 (43.8%) | 38 (41.3%) | 0.905 (0.475–1.725) | 0.761 |
Anti-HCV | ||||
Positive | 31 (48.4%) | 40 (43.5%) | 0.819 (0.432–1.554) | 0.541 |
Liver cirrhosis | ||||
Positive | 53 (82.8%) | 77 (83.7%) | 1.065 (0.454–2.500) | 0.884 |
Variable | Genotypic Frequencies | |||
---|---|---|---|---|
CC (%) (n = 100) | CT + TT (%) (n = 56) | OR (95% CI) | p Value | |
Clinical stage | ||||
Stage III/IV | 34 (34%) | 15 (26.8%) | 0.710 (0.345–1.462) | 0.353 |
Tumor size | ||||
>T2 | 34 (34%) | 15 (26.8%) | 0.710 (0.345–1.462) | 0.353 |
Lymph node metastasis | ||||
Yes | 5 (5%) | 0 (0%) | NA | NA |
Distant metastasis | ||||
Yes | 6 (6%) | 1 (1.8%) | 0.285 (0.033–2.428) | 0.251 |
Vascular invasion | ||||
Yes | 18 (18%) | 7 (12.5%) | 0.651 (0.254–1.669) | 0.371 |
Child–Pugh grade | ||||
B or C | 19 (19%) | 10 (17.9%) | 0.927 (0.397–2.162) | 0.860 |
HBsAg | ||||
Positive | 36 (36%) | 30 (53.6%) | 2.051 (1.055–3.990) | 0.034 * |
Anti-HCV | ||||
Positive | 48 (48%) | 23 (41.1%) | 0.755 (0.390–1.463) | 0.405 |
Liver cirrhosis | ||||
Positive | 80 (80%) | 50 (89.3%) | 2.083 (0.783–5.542) | 0.141 |
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Yuan, L.-T.; Chang, J.-H.; Lee, H.-L.; Yang, Y.-C.; Su, S.-C.; Lin, C.-L.; Yang, S.-F.; Chien, M.-H. Genetic Variants of lncRNA MALAT1 Exert Diverse Impacts on the Risk and Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma. J. Clin. Med. 2019, 8, 1406. https://doi.org/10.3390/jcm8091406
Yuan L-T, Chang J-H, Lee H-L, Yang Y-C, Su S-C, Lin C-L, Yang S-F, Chien M-H. Genetic Variants of lncRNA MALAT1 Exert Diverse Impacts on the Risk and Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma. Journal of Clinical Medicine. 2019; 8(9):1406. https://doi.org/10.3390/jcm8091406
Chicago/Turabian StyleYuan, Lan-Ting, Jer-Hwa Chang, Hsiang-Lin Lee, Yi-Chieh Yang, Shih-Chi Su, Chien-Liang Lin, Shun-Fa Yang, and Ming-Hsien Chien. 2019. "Genetic Variants of lncRNA MALAT1 Exert Diverse Impacts on the Risk and Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma" Journal of Clinical Medicine 8, no. 9: 1406. https://doi.org/10.3390/jcm8091406