Table 12 Dysregulation of CDK4/6 in clinical samples
From: A review on the role of cyclin dependent kinases in cancers
Tumor type | Samples | Expression (Tumor vs. Normal) | Kaplan–Meier analysis (impact of regulators dysregulation) | Multivariate Cox regression analysis | Association of dysregulation of regulators with clinicopathologic characteristics | References |
|---|---|---|---|---|---|---|
Acute myeloid leukemia | 24 patients with AML and normal controls | Up of miR-362-5p (which indirectly regulated CDK4) | _ | _ | _ | [202] |
Bladder cancer | 27 tumor tissues | Up of CDK4 and down of miR-124 | _ | _ | _ | [203] |
25 PTANC | Down of miR-195 (which suppressed CDK4) | Poor OS | _ | _ | [204] | |
83 PTANC | Down of miR-124 (which suppressed CDK4) | Poor OS | _ | _ | [205] | |
Breast cancer | TCGA dataset | Up-regulation of CDK6 in FAT1-deleted samples than those in FAT1 wild-type samples up-regulation of CDK4 than CDK6 transcripts in most ER + breast cancers but not in FAT1 negative tumors | _ | _ | _ | [196] |
77 cases of HER2 + and 53 cases of HER2- breast cancer | Up-regulation of CDK4/6 and pRb levels in HER2 + | _ | _ | _ | [334] | |
GEO database (GSE4922, GSE6532, GSE20194, GSE26459, GSE98987) | Up-regulation of HMGB1 in tamoxifen‐resistant group | Shorter PFS for HR + BC patients with endocrine therapy after surgery | [215] | |||
40 PTANC | Down of miR-124 (which suppressed CDK4) | _ | _ | _ | [219] | |
40 PTANC | Down of miR-124 (which suppressed CDK4) | Poor OS | Expression of miR-124 was found to be correlated with poor survival | advanced pathological stages | [222] | |
60 PTANC | Down of miR-1301-3p (which indirectly suppressed CDK4) | _ | _ | tumor size and clinical stage | [224] | |
TCGA dataset: 658 tumor and 86 normal breast tissue | Down of miR-34c (which suppressed CDK4) | _ | _ | _ | [226] | |
Cervical cancer | GEO database (GSE102686) 60 PTANC | Up of circ_0000326 (which indirectly regulated CDK4) | _ | _ | _ | [227] |
Clear cell renal cell carcinoma | 41 PTANC 90 PTANC | Down of miR-1 (which suppressed CDK4) | Poor OS | _ | clinical Stage and T classification | [228] |
TCGA dataset | Up of DMDRMR (which indirectly regulated CDK4) | Poor OS | _ | pathologic stage, tumor size, metastatic status, and Fuhrman grade | [229] | |
41 PTANC | Down of miR-206 (which directly suppressed CDK4) | _ | _ | _ | [230] | |
Colon cancer | 25 PTANC | Up of HAGLR circMMP9 (which regulated CDK4 and CDK6) | _ | _ | _ | [231] |
Colorectal cancer | 60 PTANC | Up of MCM3AP-AS1 (which regulated CDK4) | Poor OS | _ | _ | [233] |
116 PTANC | Down of miR-142-3p (which suppressed CDK4) | Poor OS | _ | _ | [234] | |
TCGA dataset | Up of CDK4/6 | _ | _ | _ | [235] | |
3 patients with mild myelosuppression and 3 with severe myelosuppression and (MildA, MildB, SevereA, and SevereB groups) | Up of miR-122-5p (which suppressed CDK4) in the SevereB and MildB groups than SevereA and MildA groups | _ | _ | severity of myelosuppression caused by chemotherapy | [335] | |
92 PTANC | Down of miR-875-5p (which indirectly suppressed CDK4) | Poor OS | _ | tumor size, differentiation, TNM stage, and lymph node metastasis | [236] | |
GSE167326: 150 PTANC | Down of uc.77- (which indirectly suppressed CDK4) | _ | _ | _ | [237] | |
67 PTANC | Up of LINC00665 (which indirectly regulated CDK4) | _ | _ | _ | [238] | |
10 PTANC | Down of miR-29a-3p (which indirectly regulated CDK4) | _ | _ | _ | [239] | |
Epithelial ovarian cancer | 32 patients and 20 controls | Up of PCAT-1 (which upregulated CDK4) | _ | _ | larger tumor sizes and advanced tumor grades | [240] |
Esophageal cancer | 20 PTANC | Up of CDK4 and Down of miR-486 | _ | _ | _ | [241] |
18 PTANC | Down of miR-124 (which suppressed CDK4) | _ | _ | _ | [242] | |
Esophageal squamous cell carcinoma | 34 PTANC | Up of CDK4 and Down of miR-1 (which suppressed CDK4) | _ | _ | _ | [243] |
Ewing's sarcoma | Ewing’s sarcoma patients and normal controls | Up of DLX6-AS1 (which regulated CDK4) | _ | _ | _ | [244] |
Gastric cancer | TCGA dataset: 446 tumor tissues and 15 normal tissues 60 PTANC | Up of miR-1301-3p(which indirectly upregulated CDK4) | _ | _ | _ | [247] |
27 PTANC | Up of Linc-ROR (which indirectly upregulated CDK4) | Poor OS | _ | _ | [252] | |
50 PTANC | Down of miR-29a-3p (which indirectly suppressed CDK4) | _ | _ | _ | [253] | |
GEO dataset 26 tumor tissues and 14 normal tissues | Up of GCRL1 (which regulated CDK4) | _ | _ | _ | [254] | |
Glioblastoma multiforme | 87 glioblastoma multiforme tissue samples | Up of CDK4 | _ | _ | radio-resistance | [258] |
25 tumor tissues and 14 normal tissues TCGA dataset | Down of miR-138(which indirectly suppressed CDK4) | Poor OS and PFS | _ | _ | [259] | |
18 PTANC | Up of circMMP9 (which regulated CDK4) | _ | _ | _ | [260] | |
Glioma | 12 glioma tissues of high grade and 6 normal tissues | Up-regulation of CDK4 | _ | _ | _ | [261] |
37 tumor tissues and 10 normal tissues | Up of HMMR-AS1 (which indirectly regulated CDK4) | Poor OS | _ | advanced stage | [262] | |
H. pylori related gastric cancer | 50 pairs of H. pylori positive and negative tissues | Down of miR-101 in H. pylori infected tissues (which indirectly suppressed CDK4) | _ | _ | _ | [263] |
Head and neck mucosal melanoma | 29 HNMM tissue samples (16 OMM and 13 SNMM) | Up-regulation of CDK4 in five samples (up-regulation in OMM samples than in SNMM) samples | _ | _ | _ | [264] |
Hepatocellular carcinoma | 63 PTANC and 40 healthy controls | Up of hsa_circ_0016788 (which regulated CDK4) | _ | _ | _ | [268] |
135 PTANC | Up of CCDC144NL-AS1 (which indirectly regulated CDK4) | Poor OS | _ | HBV and HCV infection, cirrhosis state, differentiation state, T stage, and the N stage of patients | [270] | |
48 PTANC | Up of circSP3 (which regulated CDK4) | _ | _ | tumor size and TNM stage | [273] | |
GEO database (GSE65485) and TCGA dataset 80 PTANC | Up of VPS9D1-AS1 (which indirectly upregulated CDK4) | Poor OS | _ | tumor size and more advanced tumor, TNM stage | [24] | |
Leiomyosarcoma | a larger cohort of 99 patients with 159 tumor samples | Up-regulation of CDK4/6 (92 were positive for CDK4, 138 for CDK6) | _ | _ | _ | [275] |
Lung cancer | 26 PTANC | Up of LINC01194 (which regulated CDK4) | _ | _ | gender, tumor size, TNM stage and lymph node metastasis | [278] |
35 PTANC | Up of hsa_circ_0014235 (which regulated CDK4 and CDK6) | _ | _ | _ | [279] | |
56 PTANC 38 PTANC | Down of miR-613 (which suppressed CDK4) | Poor OS | _ | _ | [280] | |
GEO database (GSE64591: 100 PTANC) | Down of miR-34b-3p (which suppressed CDK4) | _ | _ | _ | [281] | |
11 PTANC | Up of CDK4 and circRNA_001010 | _ | _ | _ | [282] | |
64 PTANC | Down of miR-340 (which suppressed CDK4) | Poor OS | _ | lymph node metastasis, larger tumor size, advanced TNM stage and poor prognosis | [283] | |
38 PTANC | Up of CDK4 | _ | _ | tumor stage | [284] | |
39 PTANC | Down of miR-326 (which indirectly suppressed CDK4) | Poor OS | _ | _ | [285] | |
39 PTANC | Down of miR-134 (which indirectly suppressed CDK4) | Poor OS | _ | tumor size, smoking history, TNM stage, and lymph node metastasis | [285] | |
71 PTANC | Down of miR-98 (which indirectly suppressed CDK4) | Poor OS | _ | _ | [286] | |
41 PTANC | up of miR-1290 (which indirectly upregulated CDK4) | _ | _ | lymph node metastasis and advanced tumor stage | [287] | |
15 PTANC | Up of CDK4 and Up of circHIPK3 (which indirectly upregulated CDK4) | _ | _ | _ | [288] | |
80 PTANC | Down of miR-593 (which indirectly suppressed CDK4) | Poor OS | _ | tumor size, lymph node metastasis, distant metastasis, and advanced pathological TNM stage | [289] | |
30 PTANC | Up of lncSENCR (which indirectly regulated CDK4) | _ | _ | _ | [291] | |
15 PTANC 10 PTANC | Down of miR-545 (which directly suppressed CDK4) | _ | _ | _ | [292] | |
32 PTANC | Down of linc00703 (which affected expression of CDK4) | _ | _ | _ | [293] | |
Melanoma | 3 PTANC 43 tumor tissues 18 PTANC | Up of hsa_circ_0025039 (which regulated CDK4) | Poor OS | _ | pathological node status, pathological metastasis status and clinical stage | [304] |
36 melanoma patients and 16 healthy controls | Down of miR-206 (which directly suppressed CDK4) | _ | _ | _ | [305] | |
Multiple myeloma | 28 tumor tissues and 15 healthy controls | Down of miR-338-3p (which directly suppressed CDK4) | _ | _ | _ | [307] |
Nasopharyngeal carcinoma | 56 PTANC | Up of CDK4 and Down of miR-539 (which suppressed CDK4) | _ | _ | _ | [310] |
7 NPC and 7 normal NPE tissues 20 NPC samples and 14 inflammatory NPE samples 130 tumor samples | Up of RP11-624L4.1 (which interacted with CDK4) | Poor OS and DFS | RP11-624L4.1 expression, clinical stage, N stage, M stage, T stage were correlated with OS | T stage, N stage, M stage, clinical stage, survival state, and relapse | [61] | |
Oral squamous cell carcinoma | 24 PTANC | Up of MMP1 (which regulated CDK4) | _ | _ | _ | [311] |
80 PTANC | Up of CDK4 and Down of miR-198 (which suppressed CDK4) | Poor OS and DFS | _ | _ | [312] | |
45 PTANC | Down of miR-519d-3p (which indirectly suppressed CDK4) | _ | _ | higher tumor grade | [313] | |
10 PTANC | Down of miR-9 | _ | _ | _ | [314] | |
Osteosarcoma | 5 PTANC | Up of 91 H (which affected the methylation of CDK4 promoter) | _ | _ | _ | [317] |
Ovarian cancer | TCGA, GEO and GTEx databases | Up-regulation of CDK4/6 | Shorter OS for higher expression of CDK6 | _ | immunosuppressive state of OC | [319] |
TCGA dataset (n = 369) | Up-regulation of COL6A3 (which regulated CDK4/6) | Shorter OS | _ | advanced-stage carcinoma | [330] | |
92 patients | Up of CDK4 and Down of miR-506 (which suppressed CDK4) | _ | _ | _ | [321] | |
Papillary thyroid cancer | 49 PTANC | Down of miR-1256 (which indirectly regulated CDK4) | _ | _ | tumor size and TNM stage | [326] |
Prostate cancer | 73 PTANC | Up of miR-96 (which indirectly upregulated CDK4) | _ | _ | higher PSA level, lymph node metastasis, pathologic stage and distant metastasis | [328] |
60 PTANC | Up of CDK4 and Up of NR2F2-AS1 (which upregulated CDK4) | Poor OS | _ | _ | [329] |