Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: TERF2IP

Gene summary for TERF2IP

Gene summary.

Gene information	Species	Human
	Gene symbol	TERF2IP
	Gene ID	54386
	Gene name	TERF2 interacting protein
	Gene Alias	DRIP5
	Cytomap	16q23.1
	Gene Type	protein-coding
	GO ID	GO:0000018
	UniProtAcc	Q9NYB0

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
54386	TERF2IP	LZE4T	Human	Esophagus	ESCC	1.98e-15	5.19e-01	0.0811
54386	TERF2IP	LZE7T	Human	Esophagus	ESCC	9.20e-10	2.83e-01	0.0667
54386	TERF2IP	LZE8T	Human	Esophagus	ESCC	7.07e-04	-2.15e-01	0.067
54386	TERF2IP	LZE20T	Human	Esophagus	ESCC	2.61e-10	3.45e-01	0.0662
54386	TERF2IP	LZE22D1	Human	Esophagus	HGIN	9.62e-04	-2.74e-02	0.0595
54386	TERF2IP	LZE22T	Human	Esophagus	ESCC	3.18e-04	4.21e-01	0.068
54386	TERF2IP	LZE24T	Human	Esophagus	ESCC	2.51e-28	7.66e-01	0.0596
54386	TERF2IP	LZE21T	Human	Esophagus	ESCC	5.27e-07	5.02e-01	0.0655
54386	TERF2IP	LZE6T	Human	Esophagus	ESCC	6.18e-05	-1.48e-01	0.0845
54386	TERF2IP	P1T-E	Human	Esophagus	ESCC	3.23e-28	1.22e+00	0.0875
54386	TERF2IP	P2T-E	Human	Esophagus	ESCC	3.72e-28	5.70e-01	0.1177
54386	TERF2IP	P4T-E	Human	Esophagus	ESCC	4.12e-44	8.92e-01	0.1323
54386	TERF2IP	P5T-E	Human	Esophagus	ESCC	6.80e-29	8.42e-01	0.1327
54386	TERF2IP	P8T-E	Human	Esophagus	ESCC	9.45e-40	8.77e-01	0.0889
54386	TERF2IP	P9T-E	Human	Esophagus	ESCC	3.46e-16	4.15e-01	0.1131
54386	TERF2IP	P10T-E	Human	Esophagus	ESCC	8.29e-34	5.77e-01	0.116
54386	TERF2IP	P11T-E	Human	Esophagus	ESCC	1.61e-24	9.58e-01	0.1426
54386	TERF2IP	P12T-E	Human	Esophagus	ESCC	3.63e-35	8.44e-01	0.1122
54386	TERF2IP	P15T-E	Human	Esophagus	ESCC	6.87e-39	8.27e-01	0.1149
54386	TERF2IP	P16T-E	Human	Esophagus	ESCC	2.05e-36	8.50e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:00330449	Esophagus	HGIN	regulation of chromosome organization	51/2587	187/18723	8.91e-07	3.61e-05	51
GO:004312220	Esophagus	HGIN	regulation of I-kappaB kinase/NF-kappaB signaling	63/2587	249/18723	8.91e-07	3.61e-05	63
GO:000724918	Esophagus	HGIN	I-kappaB kinase/NF-kappaB signaling	67/2587	281/18723	3.84e-06	1.29e-04	67
GO:001063920	Esophagus	HGIN	negative regulation of organelle organization	79/2587	348/18723	4.12e-06	1.37e-04	79
GO:004312317	Esophagus	HGIN	positive regulation of I-kappaB kinase/NF-kappaB signaling	49/2587	186/18723	4.22e-06	1.40e-04	49
GO:000072318	Esophagus	HGIN	telomere maintenance	38/2587	131/18723	4.38e-06	1.42e-04	38
GO:003220416	Esophagus	HGIN	regulation of telomere maintenance	27/2587	80/18723	4.83e-06	1.56e-04	27
GO:005105214	Esophagus	HGIN	regulation of DNA metabolic process	79/2587	359/18723	1.38e-05	3.85e-04	79
GO:200102019	Esophagus	HGIN	regulation of response to DNA damage stimulus	52/2587	219/18723	5.00e-05	1.19e-03	52
GO:007189710	Esophagus	HGIN	DNA biosynthetic process	44/2587	180/18723	8.97e-05	1.96e-03	44
GO:004593626	Esophagus	HGIN	negative regulation of phosphate metabolic process	89/2587	441/18723	1.24e-04	2.54e-03	89
GO:001056326	Esophagus	HGIN	negative regulation of phosphorus metabolic process	89/2587	442/18723	1.34e-04	2.71e-03	89
GO:00701987	Esophagus	HGIN	protein localization to chromosome, telomeric region	12/2587	29/18723	2.48e-04	4.38e-03	12
GO:004232620	Esophagus	HGIN	negative regulation of phosphorylation	78/2587	385/18723	2.77e-04	4.77e-03	78
GO:000700417	Esophagus	HGIN	telomere maintenance via telomerase	21/2587	69/18723	2.80e-04	4.80e-03	21
GO:00322007	Esophagus	HGIN	telomere organization	38/2587	159/18723	4.23e-04	6.39e-03	38
GO:001083318	Esophagus	HGIN	telomere maintenance via telomere lengthening	23/2587	81/18723	4.52e-04	6.62e-03	23
GO:00064735	Esophagus	HGIN	protein acetylation	45/2587	201/18723	6.17e-04	8.58e-03	45
GO:000193320	Esophagus	HGIN	negative regulation of protein phosphorylation	69/2587	342/18723	6.81e-04	9.26e-03	69
GO:000627810	Esophagus	HGIN	RNA-dependent DNA biosynthetic process	21/2587	75/18723	9.58e-04	1.21e-02	21

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

TERF2IP

SNV

Missense_Mutation

c.922N>G

p.Gln308Glu

p.Q308E

Q9NYB0

protein_coding

tolerated(0.28)

benign(0.001)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TERF2IP

SNV

Missense_Mutation

rs527404806

c.839G>A

p.Cys280Tyr

p.C280Y

Q9NYB0

protein_coding

tolerated(0.14)

possibly_damaging(0.854)

TCGA-B6-A0WY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TERF2IP

insertion

Frame_Shift_Ins

novel

c.900_901insATTGTTGCCTTTTGTAGTCTGTTTTATTATTTGATATTTG

p.Glu301IlefsTer29

p.E301Ifs*29

Q9NYB0

protein_coding

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TERF2IP

SNV

Missense_Mutation

novel

c.506N>C

p.Lys169Thr

p.K169T

Q9NYB0

protein_coding

deleterious(0.01)

probably_damaging(0.963)

TCGA-EA-A3QD-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

TERF2IP

SNV

Missense_Mutation

c.1194G>T

p.Lys398Asn

p.K398N

Q9NYB0

protein_coding

deleterious_low_confidence(0)

benign(0.006)

TCGA-CA-6718-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

TERF2IP

SNV

Missense_Mutation

rs367821647

c.1052C>T

p.Ala351Val

p.A351V

Q9NYB0

protein_coding

deleterious(0.04)

benign(0.007)

TCGA-AG-A00H-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Chemotherapy

5-fluorouracil

TERF2IP

SNV

Missense_Mutation

rs367571165

c.1190N>A

p.Arg397Gln

p.R397Q

Q9NYB0

protein_coding

tolerated(0.12)

probably_damaging(0.988)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

TERF2IP

SNV

Missense_Mutation

rs148810861

c.1105N>T

p.Asp369Tyr

p.D369Y

Q9NYB0

protein_coding

deleterious(0)

probably_damaging(0.96)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TERF2IP

SNV

Missense_Mutation

novel

c.745N>A

p.Ala249Thr

p.A249T

Q9NYB0

protein_coding

tolerated(0.53)

benign(0)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

TERF2IP

SNV

Missense_Mutation

c.832A>G

p.Thr278Ala

p.T278A

Q9NYB0

protein_coding

tolerated(0.11)

benign(0.225)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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