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: TSN

Gene summary for TSN

Gene summary.

Gene information	Species	Human
	Gene symbol	TSN
	Gene ID	7247
	Gene name	translin
	Gene Alias	BCLF-1
	Cytomap	2q14.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	B3KRM8

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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
7247	TSN	LZE2T	Human	Esophagus	ESCC	1.59e-06	6.31e-01	0.082
7247	TSN	LZE4T	Human	Esophagus	ESCC	2.82e-15	5.49e-01	0.0811
7247	TSN	LZE5T	Human	Esophagus	ESCC	4.63e-02	2.43e-01	0.0514
7247	TSN	LZE7T	Human	Esophagus	ESCC	8.07e-11	8.11e-01	0.0667
7247	TSN	LZE8T	Human	Esophagus	ESCC	2.49e-05	2.78e-01	0.067
7247	TSN	LZE20T	Human	Esophagus	ESCC	3.48e-03	1.95e-01	0.0662
7247	TSN	LZE22D1	Human	Esophagus	HGIN	7.11e-03	9.13e-02	0.0595
7247	TSN	LZE22T	Human	Esophagus	ESCC	4.76e-03	5.49e-01	0.068
7247	TSN	LZE24T	Human	Esophagus	ESCC	2.69e-21	4.09e-01	0.0596
7247	TSN	LZE21T	Human	Esophagus	ESCC	5.63e-05	3.23e-01	0.0655
7247	TSN	LZE6T	Human	Esophagus	ESCC	1.14e-14	3.18e-01	0.0845
7247	TSN	P1T-E	Human	Esophagus	ESCC	7.41e-09	2.35e-01	0.0875
7247	TSN	P2T-E	Human	Esophagus	ESCC	3.26e-32	5.99e-01	0.1177
7247	TSN	P4T-E	Human	Esophagus	ESCC	1.28e-37	8.04e-01	0.1323
7247	TSN	P5T-E	Human	Esophagus	ESCC	5.12e-28	5.25e-01	0.1327
7247	TSN	P8T-E	Human	Esophagus	ESCC	1.63e-29	4.87e-01	0.0889
7247	TSN	P9T-E	Human	Esophagus	ESCC	2.38e-10	2.09e-01	0.1131
7247	TSN	P10T-E	Human	Esophagus	ESCC	5.38e-66	1.04e+00	0.116
7247	TSN	P11T-E	Human	Esophagus	ESCC	1.67e-21	8.62e-01	0.1426
7247	TSN	P12T-E	Human	Esophagus	ESCC	9.28e-91	1.68e+00	0.1122

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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:00158331	Colorectum	SER	peptide transport	58/2897	264/18723	3.08e-03	2.70e-02	58
GO:00301001	Colorectum	SER	regulation of endocytosis	48/2897	211/18723	3.29e-03	2.82e-02	48
GO:0060996	Colorectum	SER	dendritic spine development	26/2897	99/18723	3.83e-03	3.17e-02	26
GO:00900871	Colorectum	SER	regulation of peptide transport	46/2897	202/18723	3.86e-03	3.18e-02	46
GO:00027911	Colorectum	SER	regulation of peptide secretion	45/2897	200/18723	5.35e-03	4.03e-02	45
GO:00510471	Colorectum	SER	positive regulation of secretion	65/2897	310/18723	5.71e-03	4.19e-02	65
GO:00902761	Colorectum	SER	regulation of peptide hormone secretion	44/2897	196/18723	6.08e-03	4.42e-02	44
GO:00508081	Colorectum	SER	synapse organization	85/2897	426/18723	7.17e-03	4.99e-02	85
GO:00226042	Colorectum	MSS	regulation of cell morphogenesis	103/3467	309/18723	2.70e-10	2.56e-08	103
GO:00161972	Colorectum	MSS	endosomal transport	79/3467	230/18723	7.04e-09	4.39e-07	79
GO:00725831	Colorectum	MSS	clathrin-dependent endocytosis	22/3467	47/18723	8.74e-06	2.16e-04	22
GO:00301002	Colorectum	MSS	regulation of endocytosis	63/3467	211/18723	4.05e-05	7.66e-04	63
GO:00160492	Colorectum	MSS	cell growth	123/3467	482/18723	7.15e-05	1.21e-03	123
GO:00068981	Colorectum	MSS	receptor-mediated endocytosis	69/3467	244/18723	1.18e-04	1.82e-03	69
GO:00510561	Colorectum	MSS	regulation of small GTPase mediated signal transduction	82/3467	302/18723	1.31e-04	1.99e-03	82
GO:00015582	Colorectum	MSS	regulation of cell growth	105/3467	414/18723	2.97e-04	3.90e-03	105
GO:00458071	Colorectum	MSS	positive regulation of endocytosis	33/3467	100/18723	3.73e-04	4.72e-03	33
GO:00158332	Colorectum	MSS	peptide transport	71/3467	264/18723	4.79e-04	5.60e-03	71
GO:19035321	Colorectum	MSS	positive regulation of secretion by cell	74/3467	282/18723	7.93e-04	8.36e-03	74
GO:00510472	Colorectum	MSS	positive regulation of secretion	80/3467	310/18723	8.55e-04	8.75e-03	80

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
TSN	CD8TCM	Colorectum	AD	CHI3L2,SPARCL1,TIPRL, etc.	7.32e-02
TSN	MAST	Colorectum	ADJ	CHI3L2,SPARCL1,TIPRL, etc.	9.13e-02
TSN	CD8TCM	Colorectum	ADJ	CHI3L2,SPARCL1,TIPRL, etc.	3.24e-02
TSN	CD8TCM	Colorectum	FAP	CHI3L2,SPARCL1,TIPRL, etc.	5.36e-02
TSN	GC	Colorectum	MSI-H	CHI3L2,SPARCL1,TIPRL, etc.	7.18e-02
TSN	GC	Colorectum	SER	CHI3L2,SPARCL1,TIPRL, etc.	3.22e-02
TSN	DIFF	Esophagus	Healthy	MSMO1,NMU,RHEB, etc.	1.12e-01

∗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

TSN

insertion

In_Frame_Ins

novel

c.453_453+1insTCTTTATTA

p.Ser152_Arg153insLeuLeuSer

p.S152_R153insLLS

Q15631

protein_coding

TCGA-A8-A09T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

TSN

SNV

Missense_Mutation

c.464C>A

p.Ser155Tyr

p.S155Y

Q15631

protein_coding

deleterious(0)

probably_damaging(0.928)

TCGA-AD-5900-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TSN

SNV

Missense_Mutation

c.475N>A

p.Val159Met

p.V159M

Q15631

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-CA-6716-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Chemotherapy

oxaliplatin

TSN

SNV

Missense_Mutation

c.268N>T

p.His90Tyr

p.H90Y

Q15631

protein_coding

deleterious(0.01)

possibly_damaging(0.895)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

TSN

SNV

Missense_Mutation

novel

c.586N>A

p.Asp196Asn

p.D196N

Q15631

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

TSN

SNV

Missense_Mutation

novel

c.634N>A

p.Leu212Ile

p.L212I

Q15631

protein_coding

tolerated(0.22)

possibly_damaging(0.748)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

TSN

SNV

Missense_Mutation

novel

c.362N>G

p.Glu121Gly

p.E121G

Q15631

protein_coding

deleterious(0.03)

possibly_damaging(0.664)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

TSN

SNV

Missense_Mutation

c.622N>T

p.Val208Leu

p.V208L

Q15631

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

TSN

SNV

Missense_Mutation

rs774578869

c.524A>G

p.Asn175Ser

p.N175S

Q15631

protein_coding

tolerated(0.67)

benign(0.027)

TCGA-B5-A0JZ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

TSN

SNV

Missense_Mutation

c.34N>A

p.Gly12Ser

p.G12S

Q15631

protein_coding

tolerated(0.75)

benign(0.003)

TCGA-B5-A11E-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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