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: TACC2

Gene summary for TACC2

Gene summary.

Gene information	Species	Human
	Gene symbol	TACC2
	Gene ID	10579
	Gene name	transforming acidic coiled-coil containing protein 2
	Gene Alias	AZU-1
	Cytomap	10q26.13
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	B2RWP4

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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
10579	TACC2	CA_HPV_1	Human	Cervix	CC	1.88e-05	-1.05e-01	0.0264
10579	TACC2	CCI_1	Human	Cervix	CC	5.47e-15	1.28e+00	0.528
10579	TACC2	CCI_2	Human	Cervix	CC	3.24e-14	9.87e-01	0.5249
10579	TACC2	CCI_3	Human	Cervix	CC	4.91e-14	8.51e-01	0.516
10579	TACC2	HTA11_3410_2000001011	Human	Colorectum	AD	3.07e-05	-1.71e-01	0.0155
10579	TACC2	HTA11_347_2000001011	Human	Colorectum	AD	4.29e-07	4.90e-01	-0.1954
10579	TACC2	HTA11_99999971662_82457	Human	Colorectum	MSS	7.88e-06	7.49e-01	0.3859
10579	TACC2	A015-C-203	Human	Colorectum	FAP	2.98e-24	-1.80e-01	-0.1294
10579	TACC2	A015-C-204	Human	Colorectum	FAP	4.40e-04	-1.28e-01	-0.0228
10579	TACC2	A014-C-040	Human	Colorectum	FAP	6.28e-03	-1.26e-01	-0.1184
10579	TACC2	A002-C-201	Human	Colorectum	FAP	2.87e-11	-2.65e-01	0.0324
10579	TACC2	A002-C-203	Human	Colorectum	FAP	9.28e-04	6.05e-02	0.2786
10579	TACC2	A001-C-119	Human	Colorectum	FAP	1.92e-05	3.34e-02	-0.1557
10579	TACC2	A001-C-108	Human	Colorectum	FAP	6.71e-13	2.93e-03	-0.0272
10579	TACC2	A002-C-205	Human	Colorectum	FAP	3.19e-21	-5.97e-02	-0.1236
10579	TACC2	A001-C-104	Human	Colorectum	FAP	2.43e-02	6.99e-02	0.0184
10579	TACC2	A015-C-006	Human	Colorectum	FAP	7.83e-14	-2.99e-01	-0.0994
10579	TACC2	A015-C-106	Human	Colorectum	FAP	5.14e-08	-2.68e-02	-0.0511
10579	TACC2	A002-C-114	Human	Colorectum	FAP	1.17e-14	-1.31e-01	-0.1561
10579	TACC2	A015-C-104	Human	Colorectum	FAP	6.40e-28	-2.07e-01	-0.1899

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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
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00219874	Endometrium	EEC	cerebral cortex development	23/2168	114/18723	5.41e-03	3.32e-02	23
GO:00070527	Esophagus	HGIN	mitotic spindle organization	31/2587	120/18723	3.35e-04	5.50e-03	31
GO:19028507	Esophagus	HGIN	microtubule cytoskeleton organization involved in mitosis	36/2587	147/18723	3.61e-04	5.68e-03	36
GO:00070518	Esophagus	HGIN	spindle organization	42/2587	184/18723	6.07e-04	8.49e-03	42
GO:190285015	Esophagus	ESCC	microtubule cytoskeleton organization involved in mitosis	116/8552	147/18723	1.25e-16	9.91e-15	116
GO:000705214	Esophagus	ESCC	mitotic spindle organization	97/8552	120/18723	2.17e-15	1.33e-13	97
GO:000705114	Esophagus	ESCC	spindle organization	134/8552	184/18723	5.70e-14	2.87e-12	134
GO:00215436	Esophagus	ESCC	pallium development	94/8552	169/18723	5.79e-03	2.14e-02	94
GO:000705111	Liver	HCC	spindle organization	116/7958	184/18723	1.40e-08	3.40e-07	116
GO:000705211	Liver	HCC	mitotic spindle organization	80/7958	120/18723	7.43e-08	1.50e-06	80
GO:190285011	Liver	HCC	microtubule cytoskeleton organization involved in mitosis	93/7958	147/18723	2.91e-07	5.09e-06	93
GO:00219872	Lung	IAC	cerebral cortex development	27/2061	114/18723	8.78e-05	1.77e-03	27
GO:00215432	Lung	IAC	pallium development	33/2061	169/18723	7.51e-04	9.82e-03	33
GO:00309002	Lung	IAC	forebrain development	61/2061	379/18723	1.52e-03	1.61e-02	61
GO:19028503	Lung	IAC	microtubule cytoskeleton organization involved in mitosis	27/2061	147/18723	5.23e-03	3.97e-02	27
GO:003090011	Lung	AIS	forebrain development	55/1849	379/18723	2.37e-03	2.48e-02	55
GO:00070515	Lung	MIAC	spindle organization	22/967	184/18723	2.14e-04	7.50e-03	22
GO:00070523	Lung	MIAC	mitotic spindle organization	15/967	120/18723	1.32e-03	2.44e-02	15
GO:190285012	Lung	MIAC	microtubule cytoskeleton organization involved in mitosis	17/967	147/18723	1.55e-03	2.65e-02	17
GO:00070526	Oral cavity	OSCC	mitotic spindle organization	85/7305	120/18723	1.44e-12	6.23e-11	85

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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

TACC2

SNV

Missense_Mutation

novel

c.3412N>A

p.Ala1138Thr

p.A1138T

O95359

protein_coding

deleterious(0.03)

benign(0.031)

TCGA-A2-A0EW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

TACC2

SNV

Missense_Mutation

rs554116886

c.6496G>T

p.Gly2166Trp

p.G2166W

O95359

protein_coding

deleterious(0)

possibly_damaging(0.685)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

TACC2

SNV

Missense_Mutation

c.781G>A

p.Glu261Lys

p.E261K

O95359

protein_coding

deleterious(0.04)

benign(0.088)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TACC2

SNV

Missense_Mutation

c.1588G>A

p.Ala530Thr

p.A530T

O95359

protein_coding

tolerated_low_confidence(0.23)

benign(0.066)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TACC2

SNV

Missense_Mutation

rs779701973

c.2241G>A

p.Met747Ile

p.M747I

O95359

protein_coding

tolerated(0.05)

benign(0.007)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TACC2

SNV

Missense_Mutation

c.2788G>C

p.Glu930Gln

p.E930Q

O95359

protein_coding

tolerated(1)

benign(0)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TACC2

SNV

Missense_Mutation

c.4128G>C

p.Arg1376Ser

p.R1376S

O95359

protein_coding

tolerated_low_confidence(0.05)

benign(0.015)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TACC2

SNV

Missense_Mutation

rs377162544

c.3205N>A

p.Gly1069Arg

p.G1069R

O95359

protein_coding

tolerated(1)

benign(0)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TACC2

SNV

Missense_Mutation

c.8277A>G

p.Ile2759Met

p.I2759M

O95359

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TACC2

SNV

Missense_Mutation

novel

c.8666A>T

p.Asn2889Ile

p.N2889I

O95359

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-B6-A0RE-01

Breast

breast invasive 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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