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: TINF2

Gene summary for TINF2

Gene summary.

Gene information	Species	Human
	Gene symbol	TINF2
	Gene ID	26277
	Gene name	TERF1 interacting nuclear factor 2
	Gene Alias	DKCA3
	Cytomap	14q12
	Gene Type	protein-coding
	GO ID	GO:0000723
	UniProtAcc	Q9BSI4

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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
26277	TINF2	LZE4T	Human	Esophagus	ESCC	7.58e-10	3.12e-01	0.0811
26277	TINF2	LZE7T	Human	Esophagus	ESCC	6.93e-04	1.98e-01	0.0667
26277	TINF2	LZE8T	Human	Esophagus	ESCC	1.04e-06	1.70e-01	0.067
26277	TINF2	LZE20T	Human	Esophagus	ESCC	5.58e-06	1.65e-01	0.0662
26277	TINF2	LZE22T	Human	Esophagus	ESCC	8.47e-03	1.15e-01	0.068
26277	TINF2	LZE24T	Human	Esophagus	ESCC	4.45e-23	6.33e-01	0.0596
26277	TINF2	LZE6T	Human	Esophagus	ESCC	5.34e-05	2.46e-01	0.0845
26277	TINF2	P1T-E	Human	Esophagus	ESCC	3.13e-09	2.78e-01	0.0875
26277	TINF2	P2T-E	Human	Esophagus	ESCC	1.17e-17	2.73e-01	0.1177
26277	TINF2	P4T-E	Human	Esophagus	ESCC	4.15e-28	5.73e-01	0.1323
26277	TINF2	P5T-E	Human	Esophagus	ESCC	1.09e-15	3.17e-01	0.1327
26277	TINF2	P8T-E	Human	Esophagus	ESCC	1.26e-21	3.94e-01	0.0889
26277	TINF2	P9T-E	Human	Esophagus	ESCC	1.16e-16	3.26e-01	0.1131
26277	TINF2	P10T-E	Human	Esophagus	ESCC	2.37e-19	3.30e-01	0.116
26277	TINF2	P11T-E	Human	Esophagus	ESCC	6.51e-11	6.90e-01	0.1426
26277	TINF2	P12T-E	Human	Esophagus	ESCC	3.85e-56	1.04e+00	0.1122
26277	TINF2	P15T-E	Human	Esophagus	ESCC	1.04e-36	7.94e-01	0.1149
26277	TINF2	P16T-E	Human	Esophagus	ESCC	7.68e-18	2.11e-01	0.1153
26277	TINF2	P17T-E	Human	Esophagus	ESCC	4.42e-12	5.89e-01	0.1278
26277	TINF2	P19T-E	Human	Esophagus	ESCC	5.95e-08	5.12e-01	0.1662

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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
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:190435618	Skin	cSCC	regulation of telomere maintenance via telomere lengthening	32/4864	61/18723	9.07e-06	1.19e-04	32
GO:00701988	Skin	cSCC	protein localization to chromosome, telomeric region	17/4864	29/18723	2.00e-04	1.67e-03	17
GO:005067324	Skin	cSCC	epithelial cell proliferation	144/4864	437/18723	6.07e-04	4.38e-03	144
GO:2000279	Skin	cSCC	negative regulation of DNA biosynthetic process	17/4864	38/18723	9.41e-03	4.25e-02	17
GO:003304419	Thyroid	PTC	regulation of chromosome organization	102/5968	187/18723	1.04e-10	3.58e-09	102
GO:005105218	Thyroid	PTC	regulation of DNA metabolic process	171/5968	359/18723	2.52e-10	8.33e-09	171
GO:0032204110	Thyroid	PTC	regulation of telomere maintenance	52/5968	80/18723	1.15e-09	3.34e-08	52
GO:0010639112	Thyroid	PTC	negative regulation of organelle organization	163/5968	348/18723	3.04e-09	8.39e-08	163
GO:0000723111	Thyroid	PTC	telomere maintenance	74/5968	131/18723	4.85e-09	1.26e-07	74
GO:0007004111	Thyroid	PTC	telomere maintenance via telomerase	43/5968	69/18723	1.88e-07	3.48e-06	43
GO:00701989	Thyroid	PTC	protein localization to chromosome, telomeric region	22/5968	29/18723	1.44e-06	2.04e-05	22
GO:0010833111	Thyroid	PTC	telomere maintenance via telomere lengthening	46/5968	81/18723	3.10e-06	4.04e-05	46
GO:0006278110	Thyroid	PTC	RNA-dependent DNA biosynthetic process	43/5968	75/18723	4.61e-06	5.66e-05	43
GO:003221010	Thyroid	PTC	regulation of telomere maintenance via telomerase	33/5968	53/18723	5.10e-06	6.20e-05	33
GO:190435619	Thyroid	PTC	regulation of telomere maintenance via telomere lengthening	36/5968	61/18723	1.11e-05	1.22e-04	36
GO:2000278112	Thyroid	PTC	regulation of DNA biosynthetic process	55/5968	106/18723	1.45e-05	1.55e-04	55
GO:00322009	Thyroid	PTC	telomere organization	74/5968	159/18723	7.46e-05	6.43e-04	74
GO:0071897110	Thyroid	PTC	DNA biosynthetic process	82/5968	180/18723	7.98e-05	6.81e-04	82
GO:20012515	Thyroid	PTC	negative regulation of chromosome organization	43/5968	86/18723	3.49e-04	2.40e-03	43
GO:00322053	Thyroid	PTC	negative regulation of telomere maintenance	20/5968	35/18723	1.75e-03	9.51e-03	20

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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

TINF2

SNV

Missense_Mutation

novel

c.1154N>G

p.Ser385Cys

p.S385C

Q9BSI4

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.77)

TCGA-AC-A3BB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

TINF2

insertion

In_Frame_Ins

novel

c.204_205insAATCCTCCTCAGCAACAAAGACTAGCA

p.Glu68_Leu69insAsnProProGlnGlnGlnArgLeuAla

p.E68_L69insNPPQQQRLA

Q9BSI4

protein_coding

TCGA-A7-A0D9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

TINF2

insertion

Frame_Shift_Ins

novel

c.660_661insACACACAGAGC

p.Gln221ThrfsTer9

p.Q221Tfs*9

Q9BSI4

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

TINF2

insertion

Frame_Shift_Ins

novel

c.659_660insAGTTTTCTTCCGAGTAG

p.Gln221ValfsTer11

p.Q221Vfs*11

Q9BSI4

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

TINF2

insertion

In_Frame_Ins

novel

c.265_266insCTTCAGGATGTGCTGAGTTGGATGCAGCCTGGAGTCTCTATC

p.Glu89delinsAlaSerGlyCysAlaGluLeuAspAlaAlaTrpSerLeuTyrGln

p.E89delinsASGCAELDAAWSLYQ

Q9BSI4

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

TINF2

insertion

Frame_Shift_Ins

novel

c.72_73insTCTAAAACCT

p.Gly25SerfsTer115

p.G25Sfs*115

Q9BSI4

protein_coding

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TINF2

deletion

Frame_Shift_Del

novel

c.33_36delNNNN

p.Leu12AlafsTer49

p.L12Afs*49

Q9BSI4

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TINF2

SNV

Missense_Mutation

rs780611874

c.25N>T

p.Pro9Ser

p.P9S

Q9BSI4

protein_coding

deleterious(0.04)

benign(0.189)

TCGA-C5-A1MN-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

TINF2

SNV

Missense_Mutation

c.791N>A

p.Gly264Asp

p.G264D

Q9BSI4

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

TINF2

SNV

Missense_Mutation

c.29N>T

p.Ala10Val

p.A10V

Q9BSI4

protein_coding

tolerated(0.05)

benign(0.303)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

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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