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Table 1 The deregulated tRFs in cancer

From: Emerging roles of tRNA-derived fragments in cancer

Cancer type

Expression level

tRF

Sample type

Clinical significance

Ref

Breast cancer

Upregulated

SHOT-RNAs

Tissue

SHOT-RNAs are more enriched in ER+ BC tissues than triple-negative BC and normal breast tissues

[33]

tRF-19-W4PU732S

Tissue

High level expression predicts poor survival

[104]

tRF-34-RKVP4P9L5FZUHM

Tissue

High expression correlates with poor survival of BC patients

[105]

nlr-18-949M9Y0Q, nlr-20-D6PUMZQZ

Tissue

Higher levels of both tRFs predict poorer OS; In the T cell exhaustion group, low level of nlr-18-949M9Y0Q predicts better OS

[106]

tRF-32-XSXMSL73VL4YK

Tissue

No obvious correlation

[107]

nlr-31-W01KN44VD3YZE

Tissue

Not mentioned

[108]

nlr-30-W01KN44VD3YZ, nlr-32-FKSZZ6KSNNQ7Q, tRF-34-PUDP4PZKFJ7PEP

Plasma

High expression of nlr-30-W01KN44VD3YZ and tRF-34-PUDP4PZKFJ7PEP predict worse DFS and OS

[98]

tRF-32-PS5P4PW3FJHP1

Serum, Ev from serum

High diagnostic accuracy for BC is obtained in a model with miR-21-5p (3’ addition C) and miR-23a-3p

[109]

Downregulated

tRF-17-SMKVNM1, tRF-20-6NMH490V, and tRF-20-VIPZK0JN

Tissue

tRF levels decrease in metastatic samples compared to primary tumors

[42]

nlr-14-7O58FX, nlr-21-F0L9XZ30E, nlr-34-5QKDN6QQ1362HQ

Tissue

Higher level of each tRF predicts improved OS; In the T cell exhaustion group, high level of nlr-34-5QKDN6QQ1362HQ predicts improved survival

[106]

tRF-32-Q99P9P9NH57SJ, tRF-17-79MP9PP

Tissue, serum

Lower expression correlates with higher stage progression and lymph node metastasis

[107, 110, 111]

tRF-18-YRRHQFD2, tRF-18-HSQSD2D2, tRF-20-B2NZW7O6

Tissue, serum

Expression levels are also downregulated in early-stage BC patients

[112]

tDR-000620

Serum

Low tDR-000620 expression is an independent adverse predictive factor for recurrence-free survival of triple-negative BC

[113]

nlr-21-F5W8E7OME, tRF-18-18VBY9DV, tRF-23-NB57BK87DZ

Serum

Expression levels are downregulated in non-triple-negative BC

[114]

tRF-32-1HPSR9O9337KF

Plasma

tRF-32-1HPSR9O9337KF levels significantly decrease in the blood of patients with HER2+ BC reflecting tumor status (control > early cancer > metastatic cancer)

[115]

tRF-18-HR0VX6D2, iso-26-QO608YX91ZE

Plasma

They are better biomarker candidates than their corresponding miRNAs

[116]

tRF-16-87R8WPE, tRF-22-PNR8YP9LL, tRF-23-PNR8YP9LD6, tRF-16-SP5830D, tRF-24-OB1690PQIY, tRF-28-OB1690PQR304

Plasma, exosomes from plasma and tissues

Low expressed tRF-16-87R8WPE of HER2+ early BC patients correlates to worse DFS and OS

[8]

Gastric Cancer

Upregulated

tRF-19-FRJ4O1E2

Tissue

Higher tRF-19-FRJ4O1E2 correlates with higher lymph node metastasis

[117]

tRF-18-8R1546D2

Tissue

tRF-18-8R1546D2 can discriminate GC stage I-II and III-IV, lymph node metastasis and differentiation

[118]

nlr-18-08P2F5DF

Tissue

Expression is positively correlated with tumor size and the depth of tumor invasion

[119]

tRF-29-RRJ89O9NF5JP

Tissue, serum

Expression is positively correlated with the degree of lymph node metastasis and tumor grade

[120]

tRF-23-Q99P9P9NDD

Tissue, serum

Expression is positively associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion

[121]

tRF-31-U5YKFN8DYDZDD

Serum

Expression is positively associated with depth of invasion, lymph node metastasis, TNM stage, and vascular invasion

[122]

Downregulated

nlr-15-D47RMZ,nlr-17-XI61Z7Q

Tissue

Lower expression correlates with larger tumor size and poorer differentiation

[123, 124]

tRF-24-V29K9UV3IU, tRF-34-Q99P9P9NH57S15

Tissue

Not mentioned

[125127]

tRF-34-86V8WPMN1E8Y2Q

Tissue, plasma

Lower expression correlates with larger tumor size

[128]

tRF-18-79MP9P04

Tissue, plasma

Lower expression correlates with larger tumor size, TNM stage, lymph node metastasis and poorer survival

[99]

tRF-33-P4R8YP9LON4VDP

Plasma

Not mentioned

[101]

tRF-19-3L7L73JD

Plasma

Higher expression predicts smaller tumor size

[129]

Colorectal cancer

Upregulated

nlr-26-LIKFW7X7JNE

Tissue

nlr-26-LIKFW7X7JNE is upregulated in both colon adenomas and adenocarcinomas

[73]

tRF-phe-GAA-031, tRF-VAL-TCA-002

Tissue

Increased expression positively correlates with distant metastasis and clinical stage, and predicts poorer survival

[130]

tRF-32-6978WPRLXN48Q

Tissue

High tRF-32-6978WPRLXN48Q level predicts poor DFS, OS, and high recurrence

[131]

tRF-35-PW5SVP9N15WV7W

Tissue

Expression correlates positively with tumor size, but not with age, sex,

or clinical stage

[12]

tRF-34-Q99P9P9NH57S15, tRF-30-ROD8N0X0JYOY, tRF-29-R9J89O9NF5JP, tRF-18-8R1546D2

Tissue

Not mentioned

[132, 133]

tRF-33-79MP9P9NH57SD3

Tissue, serum

Increased expression is positively associated with lymph node and distant metastasis

[134]

tRF-35-PNR8YP9LON4VN1

Plasma

Increased expression positively correlates with pathological stage and metastasis

[135]

Upregulated/downregulated

tRF-18-HSRVK7D2, tRF-33-PSQP4PW3FJI0W, tRF-33-PSQP4PW3FJIKW, tRF-32-O7M8LOMLQHWU3, tRF-18-H9Q867D2, tRF-16-I3FJQSD

Tissue

They are included in a six-tRF-based prognostic model with high risk score predicting worse survival, especially for stage III patients

[133]

Downregulated

tRF-16-79MP9PE, tRF-16-RP9830D, tRF-16-RPM830E, tRF-22-WB86Q3P92, tRF-22-WE8SPOX52, tRF-22-WE8S68L52, nlr-17-863IP5J

Tissue

Not mentioned

[132, 133, 136]

Lung cancer

Upregulated

nlr-15-395P4P

Tissue

High expression is associated with postoperative recurrence and poor prognosis

[137]

nlr-34-4P5830MMUKLYHE

Tissue, serum

nlr-34-4P5830MMUKLYHE is greatly upregulated in stage III and stage IV cases, and increases with stage progression

[138]

nlr-28-PNR8YP9LONDQ

Tissue, plasma

High nlr-28-PNR8YP9LONDQ predicts poor survival of NSCLC

[139]

tRF-21-RK9P4P9L0, tRF-16-PSQP4PE

Tissue, serum

tRF-21-RKP4P9L0 is negatively associated with prognosis in lung adenocarcinoma

[140]

tRF-31-79MP9P9NH57SD

Serum

Expression is positively associated with clinical stage and the malignancy of lymph node

[141]

tRF-30-RK9P4P9L5HMV, tRF-31-RK9P4P9L5HMVE, tRF-26-MI7O3B1NR8E, tRF-27-WJ9X0UD394N, tRF-26-SP5830MMUKD, tRF-29-MIF91SS2P4IR, tRF-30-3JVIJMRPFQRD, tRF-31-ROD8N0X0JYOYE, tRF-32-ROD8N0X0JYOYO

Peripheral blood mononuclear cells

TRY-RNA signature precisely discriminates between control, lung cancer, and pulmonary tuberculosis subjects

[142]

Downregulated

nlr-29-P9MWYRKHNZI2, iso-25-QO608YX91Z, nlr-33-Z4ODD8U82KP90Q, nlr-31-SU12RXXNBZY3E

Tissue

Not mentioned

[65, 73]

tRF-16-L85J3KE

Tissue, serum

No significant correlation with prognosis is observed

[140]

AS-tDR-007872

Tissue, plasma

AS-tDR-007872 is more sensitive in distinguishing stage III and IV than stage I-II NSCLC patients

[143]

Leukemia

Upregulated

tRF-21-ZPEK45H5D

Peripheral blood mononuclear cells

Overexpression of tRF-21-ZPEK45H5D is related to poor OS of the CLL patients

[144]

Downregulated

i-tRF of tRNAGlyCCC

Peripheral blood mononuclear cells

Reduced OS for CLL patients with positive expression of this i-tRF

[145]

nlr-29-P9MWYRKHNZI2, iso-25-QO608YX91Z, nlr-33-Z4ODD8U82KP90Q, nlr-31-SU12RXXNBZY3E

Peripheral blood mononuclear cells

Not mentioned

[65, 73]

tDR-Asp family

Bone marrow

Decreased tDR-Asp can predict myelodysplastic syndromes that are likely to progress to acute myeloid leukemia

[146]

NOT significant

tRF-18-5J3KYU05, tRF-18-HR0VX6D2

Peripheral blood mononuclear cells

High expression levels are associated with inferior OS

[147, 148]

Pancreatic cancer

Upregulated

AS-tDR-000064, AS-tDR-000069, AS-tDR-000102

Tissue

Not mentioned

[149]

tRF-18-HR0VX6D2

Tissue

Not mentioned

[150]

tRF-30-6978WPRLXN4V, tRF-18-HRERXFD2

Tissue, serum

The tRF-30-6978WPRLXN4V-high and/or tRF-18-HRERXFD2-high PC patients show significantly worse prognosis

[151]

tRF-41-N5EX62Z6EXEY0VWUD, tRF-37-KSBE78YLKZKWE52, tRF-23-YOY9Q867D2

Tissue, serum

High tRF-41-N5EX62Z6EXEY0VWUD expression is associated with advanced tumor stage and liver metastasis, and predict poor OS

[152]

Downregulated

AS-tDR-001391

Tissue

Not mentioned

[149]

nlr-33-OJ5B8LK7F1BUDV

Tissue

Low expression is associated with advanced TNM stage, N stage and predicts poor survival

[153]

tRF-21-VBY9PYKHD

Tissue

Patients with low expression levels have poor prognosis

[154]

Liver cancer

Upregulated

tRF-30-PNR8YP9LON4V

Tissue

High expression predicts poor survival

[155]

tRF-40-EFOK8YR951K36D26, tRF-34-QNR8VP94FQFY1Q, tRF-32-79MP9P9NH57SJ, tRF-31-87R8WP9N1EWJ0

Plasma exosomes

Not mentioned

[156]

Ovarian cancer

Upregulated

nlr-24-5D0RKRKNFQ, nlr-25-756BIW7K5Z

Tissue

Not mentioned

[73]

tRF-32-P4R8YP9LON4V3, tRF-25-9NJ4S2I7L7

Serum

Not mentioned

[157]

i-tRFs of tRNAGlyGCC

Tissue, serum

Increased expression is associated with advanced stages, suboptimal debulking and early progression, and predicts poor OS of early ovarian cancer

[158]

tRF-03357, tRF-03358

Serum

Expression level is significantly increased in high-grade serous ovarian cancer

[159]

Downregulated

tRF-28-PNR8YO9LOND5, tRF-28-PNR8YP9LOND5

Serum

Not mentioned

[157]

Prostate cancer

Upregulated

SHOT-RNAs

Tissue

SHOT-RNAs are upregulated in AR+ prostate cancer

[33]

Bladder cancer

Upregulated

tRF-34-Q99P9P9NH57S15, tRF-32-P4R8YP9LON4V3, tRF-31-P4R8YP9LON4VD

Tissue

Not mentioned

[160]

tRF-29-PSQP4PW3FJF4

Tissue, serum

Increased expression is associated with aggressive tumor phenotype, early disease progression and poor treatment outcome

[161]

Downregulated

tRF- + 1:T20-Ser-TGA-1

Tissue

Not mentioned

[160]

Renal cancer

Downregulated

5’ halves of tRNAValAAC

Tissue

Expression level is inversely correlated with staging and grading

[162]

5’ halves of tRNAArgCCT, tRNAGluCTC,and tRNALysTTT

Tissue, serum

Lower expression levels are associated with adverse clinicopathological parameters

[163]

Esophageal squamous cell cancer

Upregulated

tRNA-GlyGCC-5

Salivary exosomes

Patients with high risk score have shorter OS and progression-free survival, and benefit more from adjuvant therapy

[164]

Multiple myeloma

Upregulated

tRF-34-86J8WPMN1E8Y2Q

Tissue

Not mentioned

[165]

tRF-18-5J3KYU05, tRF-18-HR0VX6D2

CD138 + plasma cells

The OS and PFS are significantly longer in MM patients with high tRF-18-5J3KYU05 or tRF-18-HR0VX6D2 levels

[166]

Downregulated

tRF-17-8YQ84V2

Tissue

Not mentioned

[165]

Unkown

tRF-60:77-Thr-TGT-1,tRF-22-PY5P4PZ3H

Tissue

tRF-60:77-Thr-TGT-1 is upregulated and tRF-22-PY5P4PZ3H is downregulated in relapsed/refractory MM compared with newly diagnosed MM

[103]

Cervical cancer

Upregulated

tRF-22-ZRS3S3RX5

Tissue

Expression is positively associated with the gastric subtype of endocervical adenocarcinoma

[167]

Papillary thyroid cancer

Upregulated

tRF-32-PNR8YP9LON4V3, tRF-39-0VL8K87SIRMM12E2

Tissue

Not mentioned

[168, 169]

Lymphoma

Downregulated

tRF-22-WE8SPOX52

Tissue

Not mentioned

[170]

Pharyngeal cancer

Upregulated

tRF-30-PSQP4PW3FJIK

Tissue

Increased expression closely relates to tumor staging, differentiation grade, smoking history and drinking history, and predicts metastasis

[100]

tRF-28-Q99P9P9NH50E, tRF-24-QW58309N0Y

Tissue

Not mentioned

[171]

Downregulated

tRF-22-WD8YQ84V2

Tissue

Not mentioned

[171]

Laryngeal cancer

Downregulated

tRF-33-Q1Q89P9L842205

Tissue

Low expression is closely associated with lymph node metastasis and advanced stages

[172]

Head and neck squamous cell carcinoma

Upregulated

tRF-20-S998LO9D

Tissue

High expression level is significantly associated with poor OS

[173]

Upregulated in tissue

Downregulated in serum

5’ tRNA-Val-CAC-2–1 half

Tissue, serum

Not mentioned

[174]

Uveal melanoma

Downregulated

tRF-22-BP4MJYSZH, tRF-21-45DBNIB9B

Tissue

Low expression relates to various molecular phenotypes, metastatic disease, and poor patient survival

[175]

Glioma

Downregulated

nlr-20-2IHZI73Z, tRF-18-HRE9XFD2, and tRF-22-WB86N7O52

Tissue

High expression correlates with positive IDH mutant and better survival

[176]

Cholangiocarcinoma

Upregulated

tRF-20-LE2WMK81

Tissue

Not mentioned

[177]

Downregulated

tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, tRF-39-0668K87SERM492E2

Tissue

Not mentioned

[177]

  1. The names of tRFs are converted to the standardized license plate notation as possible [21]
  2. Abbreviations: SHOT-RNAs Sex HOrmone-dependent TRNA-derived RNAs, ER Estrogen receptor, BC Breast cancer, OS Overall survival, DFS Disease-free survival, EV Extracellular vesicles, GC Gastric cancer, NSCLC Non-small cell lung cancer, CLL Chronic lymphocytic leukemia, PC Pancreatic cancer, AR Androgen receptor; MM Multiple myeloma