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: TRIB1

Gene summary for TRIB1

Gene summary.

Gene information	Species	Human
	Gene symbol	TRIB1
	Gene ID	10221
	Gene name	tribbles pseudokinase 1
	Gene Alias	C8FW
	Cytomap	8q24.13
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q96RU8

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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
10221	TRIB1	sample1	Human	Cervix	CC	1.64e-05	4.31e-01	0.0959
10221	TRIB1	sample3	Human	Cervix	CC	4.25e-02	2.03e-01	0.1387
10221	TRIB1	T1	Human	Cervix	CC	3.33e-16	5.26e-01	0.0918
10221	TRIB1	T2	Human	Cervix	CC	4.86e-05	4.85e-01	0.0709
10221	TRIB1	LZE7T	Human	Esophagus	ESCC	1.72e-03	-1.87e-01	0.0667
10221	TRIB1	LZE24T	Human	Esophagus	ESCC	7.48e-04	7.30e-01	0.0596
10221	TRIB1	LZE6T	Human	Esophagus	ESCC	7.44e-06	-5.45e-01	0.0845
10221	TRIB1	P2T-E	Human	Esophagus	ESCC	5.20e-18	6.37e-01	0.1177
10221	TRIB1	P4T-E	Human	Esophagus	ESCC	2.93e-10	8.34e-01	0.1323
10221	TRIB1	P5T-E	Human	Esophagus	ESCC	8.42e-16	8.14e-01	0.1327
10221	TRIB1	P8T-E	Human	Esophagus	ESCC	1.09e-19	1.14e+00	0.0889
10221	TRIB1	P10T-E	Human	Esophagus	ESCC	4.06e-09	-4.35e-01	0.116
10221	TRIB1	P11T-E	Human	Esophagus	ESCC	3.29e-08	1.09e+00	0.1426
10221	TRIB1	P12T-E	Human	Esophagus	ESCC	1.55e-13	7.90e-01	0.1122
10221	TRIB1	P15T-E	Human	Esophagus	ESCC	1.47e-09	1.15e+00	0.1149
10221	TRIB1	P16T-E	Human	Esophagus	ESCC	6.52e-07	3.53e-01	0.1153
10221	TRIB1	P20T-E	Human	Esophagus	ESCC	7.22e-04	5.75e-01	0.1124
10221	TRIB1	P21T-E	Human	Esophagus	ESCC	9.45e-05	4.56e-01	0.1617
10221	TRIB1	P23T-E	Human	Esophagus	ESCC	2.17e-37	2.77e+00	0.108
10221	TRIB1	P26T-E	Human	Esophagus	ESCC	3.74e-48	1.68e+00	0.1276

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:190210510	Esophagus	ESCC	regulation of leukocyte differentiation	152/8552	279/18723	1.82e-03	8.35e-03	152
GO:00486597	Esophagus	ESCC	smooth muscle cell proliferation	103/8552	184/18723	3.08e-03	1.28e-02	103
GO:00434332	Esophagus	ESCC	negative regulation of DNA-binding transcription factor activity	103/8552	185/18723	3.86e-03	1.57e-02	103
GO:000276311	Esophagus	ESCC	positive regulation of myeloid leukocyte differentiation	37/8552	58/18723	4.12e-03	1.64e-02	37
GO:00486607	Esophagus	ESCC	regulation of smooth muscle cell proliferation	100/8552	180/18723	4.76e-03	1.85e-02	100
GO:00330025	Esophagus	ESCC	muscle cell proliferation	134/8552	248/18723	4.80e-03	1.86e-02	134
GO:000276115	Esophagus	ESCC	regulation of myeloid leukocyte differentiation	69/8552	120/18723	6.00e-03	2.21e-02	69
GO:007122215	Esophagus	ESCC	cellular response to lipopolysaccharide	113/8552	209/18723	8.79e-03	3.10e-02	113
GO:00316633	Esophagus	ESCC	lipopolysaccharide-mediated signaling pathway	37/8552	60/18723	9.17e-03	3.19e-02	37
GO:007121617	Esophagus	ESCC	cellular response to biotic stimulus	131/8552	246/18723	9.85e-03	3.39e-02	131
GO:001049812	Liver	Cirrhotic	proteasomal protein catabolic process	216/4634	490/18723	2.52e-21	9.29e-19	216
GO:004217612	Liver	Cirrhotic	regulation of protein catabolic process	181/4634	391/18723	7.94e-21	2.77e-18	181
GO:000989612	Liver	Cirrhotic	positive regulation of catabolic process	215/4634	492/18723	1.13e-20	3.56e-18	215
GO:003133112	Liver	Cirrhotic	positive regulation of cellular catabolic process	190/4634	427/18723	1.94e-19	4.18e-17	190
GO:004316112	Liver	Cirrhotic	proteasome-mediated ubiquitin-dependent protein catabolic process	184/4634	412/18723	4.52e-19	8.85e-17	184
GO:190336212	Liver	Cirrhotic	regulation of cellular protein catabolic process	124/4634	255/18723	9.85e-17	1.26e-14	124
GO:004586212	Liver	Cirrhotic	positive regulation of proteolysis	163/4634	372/18723	4.18e-16	5.14e-14	163
GO:004573212	Liver	Cirrhotic	positive regulation of protein catabolic process	112/4634	231/18723	3.89e-15	4.21e-13	112
GO:190336412	Liver	Cirrhotic	positive regulation of cellular protein catabolic process	80/4634	155/18723	5.04e-13	3.86e-11	80
GO:190305012	Liver	Cirrhotic	regulation of proteolysis involved in cellular protein catabolic process	103/4634	221/18723	1.14e-12	8.61e-11	103

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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

TRIB1

SNV

Missense_Mutation

c.616N>G

p.Leu206Val

p.L206V

Q96RU8

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TRIB1

SNV

Missense_Mutation

c.1015N>A

p.Glu339Lys

p.E339K

Q96RU8

protein_coding

tolerated(0.45)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIB1

SNV

Missense_Mutation

rs138022510

c.947G>A

p.Arg316His

p.R316H

Q96RU8

protein_coding

deleterious(0.03)

probably_damaging(0.986)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

TRIB1

SNV

Missense_Mutation

c.424N>C

p.Asn142His

p.N142H

Q96RU8

protein_coding

tolerated(0.53)

benign(0.115)

TCGA-B6-A0RS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TRIB1

insertion

Frame_Shift_Ins

novel

c.565_566insACCC

p.Ile189AsnfsTer22

p.I189Nfs*22

Q96RU8

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TRIB1

insertion

Nonsense_Mutation

novel

c.566_567insTTGGGTATTTGCAAGTCTAGAGCTTTAGG

p.Val190TrpfsTer9

p.V190Wfs*9

Q96RU8

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TRIB1

insertion

Frame_Shift_Ins

novel

c.742_743insCTTGTAAGCTCCAGCATTATGAATACTATTTGGGGCTTTGCCTC

p.Tyr248SerfsTer17

p.Y248Sfs*17

Q96RU8

protein_coding

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

TRIB1

insertion

Frame_Shift_Ins

novel

c.507dupC

p.Tyr170LeufsTer40

p.Y170Lfs*40

Q96RU8

protein_coding

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TRIB1

SNV

Missense_Mutation

novel

c.974N>G

p.Glu325Gly

p.E325G

Q96RU8

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-ZJ-AB0I-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TRIB1

SNV

Missense_Mutation

rs776955393

c.1039A>G

p.Ile347Val

p.I347V

Q96RU8

protein_coding

tolerated(0.54)

benign(0)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

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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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