Background
Methods
Patient cohort from TCGA dataset
Assessment of differentially expressed lncRNAs
ccRCC prognosis capabilities based on differentially expressed lncRNAs
Clinical role of the risk score generated by the key lncRNAs
Different signaling pathways between high- and low-risk groups
Validation by Gene Expression Omnibus DataSets and International Cancer Genomics Consortium database
Results
Differentially expressed ccRCC lncRNAs
Assessment of prognosis based on differentially-expressed lncRNAs
lncRNA | Esenble ID | Location | Log2 FC | β(Cox) | SE | P-value | Exp(B) | Lower | Upper |
---|---|---|---|---|---|---|---|---|---|
CTA-384D8.35 | ENSG00000272666 | Chromosome 22: 50,542,305–50,542,906 | 2.200229534 | 0.527 | 0.153 | 0.001 | 1.695 | 1.255 | 2.289 |
CTD-2263F21.1 | ENSG00000251257 | Chromosome 5: 38,460,925–38,468,339 | 2.101799115 | 0.238 | 0.11 | 0.031 | 1.268 | 1.022 | 1.573 |
LINC01510 | ENSG00000231210 | Chromosome 7: 116,570,960–116,614,820 | − 2.298623575 | − 0.304 | 0.078 | < 0.001 | 0.738 | 0.634 | 0.859 |
RP11-352G9.1 | ENSG00000273009 | Chromosome 3: 195,913,078–195,913,683 | 2.68714083 | 0.459 | 0.144 | 0.001 | 1.583 | 1.194 | 2.097 |
RP11-395B7.2 | ENSG00000274993 | Chromosome 7: 100,963,828–100,968,124 | 3.610473993 | 0.25 | 0.107 | 0.02 | 1.284 | 1.04 | 1.584 |
RP11-426C22.4 | ENSG00000259807 | Chromosome 16: 29,217,170–29,220,031 | 2.061342232 | − 0.309 | 0.124 | 0.012 | 0.734 | 0.576 | 0.935 |
Factor | CTA-384D8.35 | CTD-2263F21.1 | LINC01510 | RP11-352G9.1 | RP11-395B7.2 | RP11-426C22.4 |
---|---|---|---|---|---|---|
Tumor stage (T3–4/T1–2) | ||||||
t | 6.217 | 2.587 | − 4.611 | 3.190 | 2.853 | 4.004 |
P | < 0.001 |
0.010
| < 0.001 |
0.002
|
0.005
| < 0.001 |
AUC (95% CIs) | 0.663 (0.614, 0.712) | 0.547 (0.495, 0.599) | 0.383 (0.333, 0.433) | 0.583 (0.531, 0.635) | 0.572 (0.522, 0.623) | 0.594 (0.542, 0.645) |
P | < 0.001 | 0.072 | < 0.001 |
0.002
|
0.006
| < 0.001 |
Lymph node metastasis (N1–NX/N0) | ||||||
t | 0.023 | − 1.612 | 0.090 | − 0.865 | 1.370 | − 0.567 |
P | 0.981 | 0.108 | 0.928 | 0.387 | 0.171 | 0.571 |
AUC (95% CIs) | 0.484 (0.435, 0.533) | 0.464 (0.414, 0.513) | 0.510 (0.460, 0.559) | 0.482 (0.433, 0.532) | 0.526 (0.477, 0.575) | 0.497 (0.448, 0.547) |
P | 0.529 | 0.149 | 0.696 | 0.479 | 0.300 | 0.911 |
Metastasis (M1–MX/M0) | ||||||
t | 4.969 | 1.338 | − 2.637 | 1.699 | 2.475 | 0.685 |
P | < 0.001 | 0.181 | 0.009 | 0.090 | 0.014 | 0.494 |
AUC (95% CIs) | 0.651 (0.592, 0.711) | 0.547 (0.489, 0.605) | 0.416 (0.357, 0.476) | 0.550 (0.491, 0.609) | 0.578 (0.517, 0.639) | 0.530 (0.470, 0.591) |
P | < 0.001 | 0.132 | 0.007 | 0.110 | 0.013 | 0.329 |
Cancer status (with tumor/tumor free) | ||||||
t | 5.324 | 1.356 | − 4.431 | 1.665 | 2.857 | 3.406 |
P | < 0.001 | 0.176 | < 0.001 | 0.097 | 0.004 | 0.001 |
AUC (95%CIs) | 0.669 (0.618, 0.721) | 0.540 (0.486, 0.594) | 0.383 (0.330, 0.436) | 0.547 (0.492, 0.601) | 0.569 (0.515, 0.623) | 0.590 (0.536, 0.644) |
P | < 0.001 | 0.151 | < 0.001 | 0.094 | 0.013 | 0.001 |
Clinical stage (III–IV/I–II) | ||||||
t | 7.074 | 2.840 | − 4.624 | 3.511 | 2.694 | 4.051 |
P | < 0.001 | 0.005 | < 0.001 | < 0.001 | 0.007 | < 0.001 |
AUC (95% CIs) | 0.685 (0.638, 0.732) | 0.556 ( 0.505, 0.607) | 0.381 (0.332, 0.430) | 0.589 (0.538, 0.640) | 0.567 (0.518, 0.617) | 0.594 (0.544, 0.645) |
P | < 0.001 |
0.031
| < 0.001 |
0.001
|
0.009
| < 0.001 |
Grade (G3–4/G1–2) | ||||||
t | 6.241 | 2.555 | − 2.324 | 2.091 | 1.963 | 4.258 |
P | < 0.001 |
0.011
|
0.021
|
0.037
| 0.050 | < 0.001 |
AUC (95% CIs) | 0.655 (0.608, 0.701) | 0.545 (0.495, 0.594) | 0.451 (0.402, 0.500) | 0.55 (0.500, 0.599) | 0.549 (0.500, 0.599) | 0.604 (0.556, 0.653) |
P | < 0.001 | 0.078 | 0.053 | 0.051 | 0.051 | < 0.001 |
Clinical role of the six-lncRNA-based risk score
Variables | Univariate | Multivariate | ||||||
---|---|---|---|---|---|---|---|---|
P
| HR | LL | UL |
P
| HR | LL | UL | |
Risk score (high-risk/low-risk) | < 0.001 | 2.372 | 1.712 | 3.288 | 0.004 | 1.693 | 1.181 | 2.425 |
Race (Asian/black/white) | 0.497 | 0.837 | 0.5 | 1.4 | 0.349 | 0.767 | 0.44 | 1.337 |
Gender (female/male) | 0.76 | 1.049 | 0.77 | 1.431 | 0.498 | 1.126 | 0.799 | 1.588 |
Age (> 60/< 60) | < 0.001 | 1.739 | 1.283 | 2.356 | 0.004 | 1.624 | 1.17 | 2.252 |
T (T3–4/T1–2) | < 0.001 | 3.152 | 2.326 | 4.272 | 0.957 | 0.983 | 0.53 | 1.823 |
N (N1–NX/N0) | 0.557 | 0.914 | 0.678 | 1.232 | 0.06 | 0.732 | 0.529 | 1.013 |
M (M1–MX/M0) | < 0.001 | 3.736 | 2.743 | 5.089 | 0.017 | 1.63 | 1.09 | 2.436 |
Cancer status (with tumor/tumor free) | < 0.001 | 5.008 | 3.611 | 6.946 | < 0.001 | 3.182 | 2.176 | 4.653 |
Clinical stage (III–IV/I–II) | < 0.001 | 3.85 | 2.802 | 5.291 | 0.232 | 1.539 | 0.759 | 3.124 |
Grade (G3–4/G1–2) | < 0.001 | 2.668 | 1.893 | 3.759 | 0.029 | 1.531 | 1.045 | 2.243 |
Parameters |
N
| t-test | ROC | Spearman | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Mean | SD |
t
|
P
| (AUC) | LL | UL |
P
|
r
|
P
| ||
Age | |||||||||||
≤ 60 | 282 | 2.551701307 | 1.446528522 | − 2.05 | 0.041 | 0.548 | 0.499 | 0.597 | 0.058 | 0.082 | 0.058 |
> 60 | 248 | 2.812258819 | 1.475766012 | ||||||||
Tumor stage | |||||||||||
T1–2 | 340 | 2.365372014 | 1.376057212 | − 6.749 | < 0.001 | 0.669 | 0.62 | 0.718 | < 0.001 | 0.281 | < 0.001 |
T3–T4 | 190 | 3.225228793 | 1.459955424 | ||||||||
Lympy node metastasis | |||||||||||
N0 | 239 | 2.692022362 | 1.38927271 | 0.262 | 0.794 | 0.481 | 0.432 | 0.531 | 0.462 | − 0.032 | 0.462 |
N1–NX | 291 | 2.658510691 | 1.526057572 | ||||||||
Metastasis | |||||||||||
M0 | 420 | 2.512539246 | 1.468891385 | − 5.073 | < 0.001 | 0.664 | 0.61 | 0.718 | < 0.001 | 0.229 | < 0.001 |
M1–MX | 108 | 3.297433572 | 1.28906475 | ||||||||
Cancer status | |||||||||||
Tumor free | 350 | 2.466519837 | 1.399223521 | − 5.376 | < 0.001 | 0.658 | 0.605 | 0.711 | < 0.001 | 0.253 | < 0.001 |
With tumor | 157 | 3.207910769 | 1.514022946 | ||||||||
Clinical stage | |||||||||||
I–II | 322 | 2.312078114 | 1.366475268 | − 7.384 | < 0.001 | 0.685 | 0.638 | 0.732 | < 0.001 | 0.313 | < 0.001 |
III–IV | 205 | 3.226306599 | 1.415145295 | ||||||||
Grading | |||||||||||
G1–2 | 241 | 2.3761705 | 1.272204534 | − 4.767 | < 0.001 | 0.614 | 0.566 | 0.662 | < 0.001 | 0.197 | < 0.001 |
G3–4 | 281 | 2.967072624 | 1.559275235 |
Functional evaluation of the differentially expressed genes in high- and low-risk groups
Name | Size | ES | NES | NOM
P
| FDR
q
| FWER
P
| Rank at max | Leading edge |
---|---|---|---|---|---|---|---|---|
KEGG_PRIMARY_IMMUNODEFICIENCY | 35 | 0.486 | 1.787836 | 0 | 0.023534 | 0.121 | 9936 | Tags = 49%, list = 18%, signal = 59% |
KEGG_OLFACTORY_TRANSDUCTION | 386 | 0.307 | 1.663547 | 0 | 0.040478 | 0.341 | 25,224 | Tags = 57%, list = 46%, signal = 104% |
KEGG_ALLOGRAFT_REJECTION | 35 | 0.429 | 1.552546 | 0.019523 | 0.067792 | 0.668 | 9137 | Tags = 31%, list = 16%, signal = 38% |
KEGG_AUTOIMMUNE_THYROID_DISEASE | 50 | 0.392 | 1.547779 | 0.00463 | 0.052901 | 0.685 | 27,174 | Tags = 72%, list = 49%, signal = 141% |
KEGG_GRAFT_VERSUS_HOST_DISEASE | 37 | 0.419 | 1.5393 | 0.011876 | 0.045754 | 0.712 | 9137 | Tags = 27%, list = 16%, signal = 32% |
KEGG_INTESTINAL_IMMUNE_NETWORK_FOR_IGA_PRODUCTION | 46 | 0.397 | 1.514021 | 0.01171 | 0.046609 | 0.784 | 12,802 | Tags = 37%, list = 23%, signal = 48% |
KEGG_TASTE_TRANSDUCTION | 50 | 0.356 | 1.395092 | 0.065789 | 0.095099 | 0.973 | 12,317 | Tags = 44%, list = 22%, signal = 57% |
KEGG_ASTHMA | 28 | 0.409 | 1.389118 | 0.073333 | 0.086951 | 0.976 | 8139 | Tags = 25%, list = 15%, signal = 29% |
KEGG_TYPE_I_DIABETES_MELLITUS | 41 | 0.345 | 1.248997 | 0.139326 | 0.192182 | 1 | 9137 | Tags = 29%, list = 16%, signal = 35% |
KEGG_ALPHA_LINOLENIC_ACID_METABOLISM | 19 | 0.405 | 1.245173 | 0.159751 | 0.177156 | 1 | 6773 | Tags = 42%, list = 12%, signal = 48% |
KEGG_LINOLEIC_ACID_METABOLISM | 29 | 0.351 | 1.201192 | 0.193059 | 0.207408 | 1 | 6773 | Tags = 31%, list = 12%, signal = 35% |
KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS | 135 | 0.243 | 1.140861 | 0.184697 | 0.265071 | 1 | 22,435 | Tags = 50%, list = 40%, signal = 84% |
KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION | 257 | 0.221 | 1.133512 | 0.114391 | 0.254958 | 1 | 11,262 | Tags = 28%, list = 20%, signal = 35% |
KEGG_HEMATOPOIETIC_CELL_LINEAGE | 85 | 0.21 | 0.916435 | 0.667494 | 0.623275 | 1 | 8343 | Tags = 20%, list = 15%, signal = 24% |
Name | Size | ES | NES | NOM
P
| FDR
q
| FWER
P
| Rank at max | Leading edge |
---|---|---|---|---|---|---|---|---|
KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS | 132 | − 0.727497 | − 3.170449 | 0 | 0 | 0 | 9024 | Tags = 67%, list = 16%, signal = 79% |
KEGG_OXIDATIVE_PHOSPHORYLATION | 118 | − 0.708458 | − 3.066339 | 0 | 0 | 0 | 10,688 | Tags = 70%, list = 19%, signal = 87% |
KEGG_PEROXISOME | 78 | − 0.755321 | − 3.048664 | 0 | 0 | 0 | 9185 | Tags = 72%, list = 17%, signal = 86% |
KEGG_ENDOCYTOSIS | 176 | − 0.666864 | − 3.027353 | 0 | 0 | 0 | 8682 | Tags = 59%, list = 16%, signal = 70% |
KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION | 44 | − 0.818906 | − 2.976677 | 0 | 0 | 0 | 5843 | Tags = 80%, list = 11%, signal = 89% |
KEGG_FOCAL_ADHESION | 197 | − 0.636304 | − 2.969007 | 0 | 0 | 0 | 9112 | Tags = 54%, list = 16%, signal = 65% |
KEGG_PARKINSONS_DISEASE | 114 | − 0.687936 | − 2.94244 | 0 | 0 | 0 | 8989 | Tags = 61%, list = 16%, signal = 73% |
KEGG_NEUROTROPHIN_SIGNALING_PATHWAY | 125 | − 0.679093 | − 2.935972 | 0 | 0 | 0 | 9509 | Tags = 62%, list = 17%, signal = 74% |
KEGG_ALZHEIMERS_DISEASE | 158 | − 0.646806 | − 2.935276 | 0 | 0 | 0 | 8989 | Tags = 56%, list = 16%, signal = 67% |
KEGG_HUNTINGTONS_DISEASE | 174 | − 0.64174 | − 2.909377 | 0 | 0 | 0 | 8989 | Tags = 56%, list = 16%, signal = 66% |
KEGG_PROSTATE_CANCER | 89 | − 0.716898 | − 2.907305 | 0 | 0 | 0 | 9112 | Tags = 63%, list = 16%, signal = 75% |
KEGG_LYSOSOME | 119 | − 0.674316 | − 2.895725 | 0 | 0 | 0 | 9385 | Tags = 64%, list = 17%, signal = 77% |
KEGG_PATHWAYS_IN_CANCER | 321 | − 0.597361 | − 2.89323 | 0 | 0 | 0 | 10,390 | Tags = 53%, list = 19%, signal = 65% |
KEGG_TIGHT_JUNCTION | 128 | − 0.653417 | − 2.876733 | 0 | 0 | 0 | 9304 | Tags = 61%, list = 17%, signal = 73% |
KEGG_WNT_SIGNALING_PATHWAY | 149 | − 0.64552 | − 2.851381 | 0 | 0 | 0 | 10,037 | Tags = 56%, list = 18%, signal = 69% |
KEGG_ADHERENS_JUNCTION | 68 | − 0.726372 | − 2.841678 | 0 | 0 | 0 | 7905 | Tags = 71%, list = 14%, signal = 82% |
KEGG_ENDOMETRIAL_CANCER | 52 | − 0.750658 | − 2.820001 | 0 | 0 | 0 | 9383 | Tags = 75%, list = 17%, signal = 90% |
KEGG_CHRONIC_MYELOID_LEUKEMIA | 73 | − 0.694979 | − 2.816546 | 0 | 0 | 0 | 9112 | Tags = 62%, list = 16%, signal = 74% |
KEGG_REGULATION_OF_ACTIN_CYTOSKELETON | 211 | − 0.606974 | − 2.81045 | 0 | 0 | 0 | 9156 | Tags = 53%, list = 17%, signal = 63% |
KEGG_CITRATE_CYCLE_TCA_CYCLE | 30 | − 0.842038 | − 2.791856 | 0 | 0 | 0 | 5709 | Tags = 83%, list = 10%, signal = 93% |
KEGG_INSULIN_SIGNALING_PATHWAY | 137 | − 0.639309 | − 2.781884 | 0 | 0 | 0 | 9112 | Tags = 56%, list = 16%, signal = 67% |
KEGG_ERBB_SIGNALING_PATHWAY | 86 | − 0.681992 | − 2.769589 | 0 | 0 | 0 | 9112 | Tags = 62%, list = 16%, signal = 74% |
Validation of these lncRNAs using Gene Expression Omnibus DataSets and International Cancer Genomics Consortium (ICGC) database
Variable | GEO | NC | KIRC | t-test | |||||
---|---|---|---|---|---|---|---|---|---|
n | mean | SD | n | mean | SD | t | P | ||
CTA-384D8.35 | GSE53757 | 72 | 5.524 | 0.1441 | 72 | 6.236 | 0.1001 | 4.054 | < 0.0001 |
CTA-384D8.35 | GSE66272 | 26 | − 0.3785 | 0.2042 | 26 | 0.1507 | 0.1633 | 2.025 | 0.0483 |