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: TANC1

Gene summary for TANC1

Gene summary.

Gene information	Species	Human
	Gene symbol	TANC1
	Gene ID	85461
	Gene name	tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 1
	Gene Alias	ROLSB
	Cytomap	2q24.2
	Gene Type	protein-coding
	GO ID	GO:0000768
	UniProtAcc	B9EK39

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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
85461	TANC1	CA_HPV_1	Human	Cervix	CC	8.44e-05	-1.88e-01	0.0264
85461	TANC1	CCI_1	Human	Cervix	CC	2.41e-19	1.45e+00	0.528
85461	TANC1	CCI_2	Human	Cervix	CC	2.27e-20	1.87e+00	0.5249
85461	TANC1	CCI_3	Human	Cervix	CC	2.93e-25	1.39e+00	0.516
85461	TANC1	HTA11_3410_2000001011	Human	Colorectum	AD	6.67e-29	-5.60e-01	0.0155
85461	TANC1	HTA11_2487_2000001011	Human	Colorectum	SER	2.76e-03	-2.37e-01	-0.1808
85461	TANC1	HTA11_3361_2000001011	Human	Colorectum	AD	8.77e-06	-5.72e-01	-0.1207
85461	TANC1	HTA11_866_3004761011	Human	Colorectum	AD	1.52e-07	-4.87e-01	0.096
85461	TANC1	HTA11_8622_2000001021	Human	Colorectum	SER	8.91e-04	-4.93e-01	0.0528
85461	TANC1	HTA11_7696_3000711011	Human	Colorectum	AD	2.85e-10	-4.52e-01	0.0674
85461	TANC1	HTA11_99999970781_79442	Human	Colorectum	MSS	8.61e-04	-3.22e-01	0.294
85461	TANC1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.68e-10	-4.73e-01	0.3005
85461	TANC1	F007	Human	Colorectum	FAP	4.20e-06	-3.82e-01	0.1176
85461	TANC1	A001-C-207	Human	Colorectum	FAP	1.87e-03	-1.76e-01	0.1278
85461	TANC1	A015-C-203	Human	Colorectum	FAP	4.08e-40	-6.35e-01	-0.1294
85461	TANC1	A015-C-204	Human	Colorectum	FAP	2.56e-08	-3.39e-01	-0.0228
85461	TANC1	A014-C-040	Human	Colorectum	FAP	7.90e-09	-6.43e-01	-0.1184
85461	TANC1	A002-C-201	Human	Colorectum	FAP	3.09e-17	-4.05e-01	0.0324
85461	TANC1	A002-C-203	Human	Colorectum	FAP	2.58e-02	-1.14e-01	0.2786
85461	TANC1	A001-C-119	Human	Colorectum	FAP	1.77e-07	-3.57e-01	-0.1557

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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
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:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:0000768	Cervix	CC	syncytium formation by plasma membrane fusion	15/2311	55/18723	2.14e-03	1.54e-02	15
GO:0140253	Cervix	CC	cell-cell fusion	15/2311	55/18723	2.14e-03	1.54e-02	15
GO:00069491	Cervix	CC	syncytium formation	15/2311	57/18723	3.13e-03	2.05e-02	15
GO:01060277	Cervix	CC	neuron projection organization	21/2311	93/18723	4.10e-03	2.54e-02	21
GO:00511464	Cervix	CC	striated muscle cell differentiation	50/2311	283/18723	5.53e-03	3.19e-02	50
GO:00094163	Cervix	CC	response to light stimulus	54/2311	320/18723	1.03e-02	4.97e-02	54
GO:0106027	Colorectum	AD	neuron projection organization	36/3918	93/18723	6.58e-05	1.07e-03	36
GO:0043954	Colorectum	AD	cellular component maintenance	26/3918	61/18723	1.04e-04	1.56e-03	26
GO:0097061	Colorectum	AD	dendritic spine organization	31/3918	84/18723	5.48e-04	5.83e-03	31
GO:0099173	Colorectum	AD	postsynapse organization	51/3918	168/18723	2.47e-03	1.90e-02	51
GO:0050808	Colorectum	AD	synapse organization	112/3918	426/18723	4.25e-03	2.92e-02	112
GO:0097062	Colorectum	AD	dendritic spine maintenance	10/3918	21/18723	5.71e-03	3.64e-02	10
GO:01060271	Colorectum	SER	neuron projection organization	33/2897	93/18723	1.64e-06	7.23e-05	33
GO:00970611	Colorectum	SER	dendritic spine organization	29/2897	84/18723	1.27e-05	4.01e-04	29
GO:00991731	Colorectum	SER	postsynapse organization	46/2897	168/18723	5.20e-05	1.25e-03	46
GO:00439541	Colorectum	SER	cellular component maintenance	22/2897	61/18723	6.47e-05	1.49e-03	22
GO:00970621	Colorectum	SER	dendritic spine maintenance	9/2897	21/18723	2.50e-03	2.33e-02	9
GO:00508081	Colorectum	SER	synapse organization	85/2897	426/18723	7.17e-03	4.99e-02	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

TANC1

SNV

Missense_Mutation

c.4186G>C

p.Ala1396Pro

p.A1396P

Q9C0D5

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

TANC1

SNV

Missense_Mutation

rs777052839

c.2433N>A

p.Met811Ile

p.M811I

Q9C0D5

protein_coding

deleterious(0)

possibly_damaging(0.739)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

TANC1

SNV

Missense_Mutation

rs372287259

c.3259N>A

p.Ala1087Thr

p.A1087T

Q9C0D5

protein_coding

deleterious(0.02)

benign(0.228)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TANC1

SNV

Missense_Mutation

rs201847551

c.4037N>A

p.Arg1346Gln

p.R1346Q

Q9C0D5

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TANC1

SNV

Missense_Mutation

rs201847551

c.4037N>A

p.Arg1346Gln

p.R1346Q

Q9C0D5

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AQ-A04H-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

TANC1

SNV

Missense_Mutation

c.677N>A

p.Ile226Asn

p.I226N

Q9C0D5

protein_coding

deleterious(0)

possibly_damaging(0.704)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

TANC1

SNV

Missense_Mutation

c.5476N>G

p.Leu1826Val

p.L1826V

Q9C0D5

protein_coding

tolerated_low_confidence(1)

benign(0)

TCGA-E2-A14Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

TANC1

SNV

Missense_Mutation

c.517A>C

p.Ile173Leu

p.I173L

Q9C0D5

protein_coding

tolerated(0.11)

benign(0.003)

TCGA-E2-A1AZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TANC1

SNV

Missense_Mutation

rs758340201

c.863N>T

p.Ala288Val

p.A288V

Q9C0D5

protein_coding

tolerated(0.31)

benign(0.01)

TCGA-E2-A1L7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

TANC1

SNV

Missense_Mutation

c.2254G>C

p.Glu752Gln

p.E752Q

Q9C0D5

protein_coding

tolerated(0.09)

benign(0.217)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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
85461	TANC1	CLINICALLY ACTIONABLE		radiotherapy		24974847

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