Background
Methods
GEO datasets and clinical information of patients with MM
Microarray analysis and lncRNA re-annotation
Identification of potential prognostic lncRNA biomarkers associated with OS in patients with MM
Statistical analysis
Functional enrichment analysis
Results
Identification of prognostic lncRNA biomarkers associated with patients’ OS from the training dataset
Ensembl id | Gene symbol | Chromosomal position |
P valuea
| Hazard ratioa
| Coefficienta
|
---|---|---|---|---|---|
ENSG00000237481 |
RP4-803 J11.2
| Chromosome 1: 229,319,403–229,323,087(+) | 1.42E-04 | 1.429 | 0.357 |
ENSG00000230424 |
RP1-43E13.2
| Chromosome 1: 19,210,501–19,240,704(+) | 0.005 | 1.656 | 0.504 |
ENSG00000259976 |
RP11-553 L6.5
| Chromosome 3: 114,314,501–114,316,179(−) | 0.007 | 0.702 | −0.354 |
ENSG00000233070 |
ZFY-AS1
| Chromosome Y: 2,966,844–3,002,626(−) | 0.002 | 0.758 | −0.276 |
Construction and validation of lncRNA-focus risk score model for predicting OS in the training dataset
Variables | Univariate analysisa
| Multivariable analysisa
| ||||
---|---|---|---|---|---|---|
HR | 95 % CI of HR |
P Value | HR | 95 % CI of HR |
P Value | |
Training dataset (n = 280) | ||||||
lncRNA-focus risk score | 2.718 | 1.937–3.815 | 7.262E-09 | 2.066 | 1.395–3.060 | 2.94E-04 |
Age | 1.032 | 1.008–1.056 | 0.008 | 1.020 | 0.997–1.044 | 0.090 |
Gender (female/male) | 0.844 | 0.556–1.280 | 0.424 | 1.047 | 0.665–1.648 | 0.842 |
Total Therapy (TT2/TT3) | 0.914 | 0.572–1.462 | 0.709 | 1.060 | 0.648–1.735 | 0.816 |
IgA isotype (N/Y) | 1.044 | 0.654–1.666 | 0.857 | 1.032 | 0.794–2.134 | 0.295 |
Serum beta 2-microglobulin ≥ 3.5 mg/L (N/Y) | 2.677 | 1.742–4.112 | 6.99E-06 | 1.733 | 1.057–2.843 | 0.029 |
C-reactive protein ≥ 8.0 mg/L (N/Y) | 1.749 | 1.155–2.648 | 0.008 | 1.008 | 0.628–1.616 | 0.975 |
Creatinine ≥ 2.0 mg/dL (177 μmol/L) (N/Y) | 3.821 | 2.338–6.245 | 8.84E-08 | 1.864 | 0.992–3.501 | 0.053 |
Lactate dehydrogenase > upper limit of normal (>190 U/L) (N/Y) | 2.651 | 1.749–4.017 | 4.33E-06 | 1.484 | 0.928–2.371 | 0.099 |
Serum albumin <35 g/ L (N/Y) | 2.003 | 1.228–3.266 | 0.005 | 1.559 | 0.929–2.618 | 0.093 |
Testing dataset (n = 279) | ||||||
lncRNA-focus risk score | 1.579 | 1.099–2.270 | 0.014 | 1.726 | 1.113–2.675 | 0.015 |
Age | 1.015 | 0.991–1.039 | 0.223 | 1.006 | 0.982–1.031 | 0.616 |
Gender (female/male) | 1.130 | 0.722–1.768 | 0.593 | 1.667 | 0.981–2.831 | 0.059 |
Total Therapy (TT2/TT3) | 0.651 | 0.368–1.150 | 0.139 | 0.590 | 0.329–1.060 | 0.077 |
IgA isotype (N/Y) | 1.189 | 0.724–1.953 | 0.494 | 1.428 | 0.837–2.438 | 0.192 |
Serum beta 2-microglobulin ≥ 3.5 mg/L (N/Y) | 1.866 | 1.206–2.888 | 0.005 | 1.470 | 0.886–2.437 | 0.136 |
C-reactive protein ≥ 8.0 mg/L (N/Y) | 1.233 | 0.786–1.932 | 0.362 | 1.158 | 0.734–1.828 | 0.529 |
Creatinine ≥ 2.0 mg/dL (177 μmol/L) (N/Y) | 1.774 | 0.937–3.359 | 0.078 | 0.954 | 0.467–1.946 | 0.896 |
Lactate dehydrogenase > upper limit of normal (>190 U/L) (N/Y) | 1.993 | 1.283–3.097 | 0.002 | 1.918 | 1.133–3.249 | 0.015 |
Serum albumin <35 g/ L (N/Y) | 1.877 | 1.055–3.340 | 0.032 | 1.791 | 0.933–3.437 | 0.080 |
Entire GSE24080 dataset (n = 559) | ||||||
lncRNA-focus risk score | 2.099 | 1.638–2.688 | 4.404E-09 | 1.905 | 1.434–2.530 | 8.65E-06 |
Age | 1.024 | 1.007–1.041 | 0.005 | 1.013 | 0.996–1.030 | 0.128 |
Gender (female/male) | 0.973 | 0.717–1.319 | 0.860 | 1.338 | 0.955–1.875 | 0.090 |
Total Therapy (TT2/TT3) | 0.797 | 0.556–1.143 | 0.218 | 0.805 | 0.554–1.168 | 0.254 |
IgA isotype (N/Y) | 1.106 | 0.787–1.555 | 0.561 | 1.261 | 0.888–1.791 | 0.194 |
Serum beta 2-microglobulin ≥ 3.5 mg/L (N/Y) | 2.236 | 1.651–3.028 | 2.0E-07 | 1.574 | 1.111–2.231 | 0.011 |
C-reactive protein ≥ 8.0 mg/L (N/Y) | 1.485 | 1.097–2.011 | 0.011 | 1.123 | 0.818–1.543 | 0.474 |
Creatinine ≥ 2.0 mg/dL (177 μmol/L) (N/Y) | 2.730 | 1.856–4.015 | 3.35E-07 | 1.377 | 0.877–2.160 | 0.165 |
Lactate dehydrogenase > upper limit of normal (>190 U/L) (N/Y) | 2.317 | 1.714–3.133 | 4.77E-08 | 1.645 | 1.180–2.294 | 0.003 |
Serum albumin <35 g/ L (N/Y) | 1.946 | 1.342–2.821 | 4.47E-04 | 1.519 | 1.028–2.245 | 0.036 |
GSE57317 dataset (n = 55)b
| ||||||
lncRNA-focus risk score | 2.640 | 1.013–6.879 | 0.047 | |||
GSE9782 dataset (n = 264) | ||||||
lncRNA-focus risk score | 1.637 | 1.107–2.42 | 0.014 | 1.909 | 1.269–2.870 | 0.002 |
Age | 1.014 | 0.998–1.03 | 0.087 | 1.016 | 0.999–1.032 | 0.054 |
Gender (female/male) | 1.334 | 0.961–1.853 | 0.086 | 1.543 | 1.098–2.169 | 0.012 |
GO terms and KEGG pathways | NO. of genes |
P-value | Fold enrichment |
---|---|---|---|
Cluster 1 (Enrichment Score: 11.01) | |||
GO:0000280 ~ nuclear division | 33 | 4.55E-14 | 5.14 |
GO:0007067 ~ mitosis | 33 | 4.55E-14 | 5.14 |
GO:0000279 ~ M phase | 40 | 6.73E-14 | 4.16 |
GO:0000087 ~ M phase of mitotic cell cycle | 33 | 7.61E-14 | 5.05 |
GO:0048285 ~ organelle fission | 33 | 1.42E-13 | 4.94 |
GO:0022403 ~ cell cycle phase | 43 | 1.43E-12 | 3.56 |
GO:0007049 ~ cell cycle | 61 | 2.78E-12 | 2.69 |
GO:0000278 ~ mitotic cell cycle | 39 | 1.25E-11 | 3.61 |
GO:0022402 ~ cell cycle process | 47 | 2.41E-10 | 2.85 |
GO:0051301 ~ cell division | 31 | 2.50E-09 | 3.60 |
GO:0000070 ~ mitotic sister chromatid segregation | 12 | 3.47E-09 | 11.42 |
GO:0000819 ~ sister chromatid segregation | 12 | 4.82E-09 | 11.11 |
GO:0007059 ~ chromosome segregation | 16 | 9.96E-09 | 6.77 |
Cluster 2 (Enrichment Score: 4.27) | |||
GO:0051276 ~ chromosome organization | 38 | 8.45E-08 | 2.68 |
GO:0016568 ~ chromatin modification | 19 | 0.001137 | 2.37 |
GO:0006325 ~ chromatin organization | 23 | 0.001656 | 2.08 |
Cluster 3 (Enrichment Score: 3.58) | |||
GO:0006260 ~ DNA replication | 20 | 2.88E-06 | 3.61 |
hsa03030:DNA replication | 7 | 9.85E-04 | 5.89 |
GO:0006261 ~ DNA-dependent DNA replication | 7 | 0.006632 | 4.13 |
Cluster 4 (Enrichment Score: 3.33) | |||
GO:0007051 ~ spindle organization | 8 | 2.94E-04 | 6.09 |
GO:0000226 ~ microtubule cytoskeleton organization | 14 | 3.64E-04 | 3.26 |
GO:0007017 ~ microtubule-based process | 19 | 4.48E-04 | 2.57 |
GO:0007010 ~ cytoskeleton organization | 26 | 0.001002 | 2.04 |
Cluster 5 (Enrichment Score: 2.59) | |||
GO:0006259 ~ DNA metabolic process | 34 | 1.31E-05 | 2.30 |
GO:0006974 ~ response to DNA damage stimulus | 21 | 0.006553 | 1.93 |
GO:0006281 ~ DNA repair | 16 | 0.019452 | 1.93 |
GO:0033554 ~ cellular response to stress | 26 | 0.025459 | 1.57 |
Cluster 6 (Enrichment Score: 2.57) | |||
GO:0008380 ~ RNA splicing | 23 | 3.03E-05 | 2.77 |
GO:0006397 ~ mRNA processing | 23 | 1.82E-04 | 2.454 |
GO:0016071 ~ mRNA metabolic process | 24 | 5.39E-04 | 2.22 |
GO:0006396 ~ RNA processing | 31 | 6.70E-04 | 1.94 |
GO:0000398 ~ nuclear mRNA splicing, via spliceosome | 11 | 0.014111 | 2.46 |
GO:0000377 ~ RNA splicing, via transesterification reactions with bulged adenosine as nucleophile | 11 | 0.014111 | 2.46 |
GO:0000375 ~ RNA splicing, via transesterification reactions | 11 | 0.014111 | 2.46 |
hsa03040:Spliceosome | 10 | 0.022065 | 2.40 |