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: CACNB2

Gene summary for CACNB2

Gene summary.

Gene information	Species	Human
	Gene symbol	CACNB2
	Gene ID	783
	Gene name	calcium voltage-gated channel auxiliary subunit beta 2
	Gene Alias	CAB2
	Cytomap	10p12.33-p12.31
	Gene Type	protein-coding
	GO ID	GO:0001505
	UniProtAcc	Q08289

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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
783	CACNB2	HTA11_2487_2000001011	Human	Colorectum	SER	1.14e-14	-8.17e-01	-0.1808
783	CACNB2	HTA11_3361_2000001011	Human	Colorectum	AD	8.85e-03	-5.46e-01	-0.1207
783	CACNB2	HTA11_5212_2000001011	Human	Colorectum	AD	4.01e-07	-9.41e-01	-0.2061
783	CACNB2	HTA11_5216_2000001011	Human	Colorectum	SER	8.29e-06	-6.41e-01	-0.1462
783	CACNB2	HTA11_7663_2000001011	Human	Colorectum	SER	1.08e-08	7.79e-01	0.0131
783	CACNB2	HTA11_7696_3000711011	Human	Colorectum	AD	3.52e-02	-2.90e-01	0.0674
783	CACNB2	HTA11_99999970781_79442	Human	Colorectum	MSS	1.11e-35	-9.20e-01	0.294
783	CACNB2	HTA11_99999965104_69814	Human	Colorectum	MSS	3.09e-02	-4.64e-01	0.281
783	CACNB2	HTA11_99999971662_82457	Human	Colorectum	MSS	1.14e-17	-6.23e-01	0.3859
783	CACNB2	HTA11_99999973899_84307	Human	Colorectum	MSS	6.19e-19	-1.12e+00	0.2585
783	CACNB2	HTA11_99999974143_84620	Human	Colorectum	MSS	2.58e-63	-1.16e+00	0.3005
783	CACNB2	A002-C-010	Human	Colorectum	FAP	3.26e-02	1.35e-01	0.242
783	CACNB2	A001-C-207	Human	Colorectum	FAP	1.23e-02	-3.62e-01	0.1278
783	CACNB2	A015-C-203	Human	Colorectum	FAP	1.37e-41	-7.17e-01	-0.1294
783	CACNB2	A015-C-204	Human	Colorectum	FAP	1.03e-12	-6.29e-01	-0.0228
783	CACNB2	A014-C-040	Human	Colorectum	FAP	1.99e-05	-5.17e-01	-0.1184
783	CACNB2	A002-C-201	Human	Colorectum	FAP	1.42e-11	-3.92e-01	0.0324
783	CACNB2	A001-C-119	Human	Colorectum	FAP	1.24e-22	-9.24e-01	-0.1557
783	CACNB2	A001-C-108	Human	Colorectum	FAP	8.33e-32	-6.67e-01	-0.0272
783	CACNB2	A002-C-205	Human	Colorectum	FAP	5.20e-29	-6.71e-01	-0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:0060249	Colorectum	AD	anatomical structure homeostasis	94/3918	314/18723	9.37e-05	1.42e-03	94
GO:0045921	Colorectum	AD	positive regulation of exocytosis	33/3918	86/18723	1.58e-04	2.20e-03	33
GO:0030048	Colorectum	AD	actin filament-based movement	44/3918	127/18723	2.31e-04	2.99e-03	44
GO:0051047	Colorectum	AD	positive regulation of secretion	90/3918	310/18723	4.11e-04	4.66e-03	90
GO:1903532	Colorectum	AD	positive regulation of secretion by cell	82/3918	282/18723	6.85e-04	7.00e-03	82
GO:0006887	Colorectum	AD	exocytosis	96/3918	352/18723	2.48e-03	1.90e-02	96
GO:0017157	Colorectum	AD	regulation of exocytosis	59/3918	202/18723	3.20e-03	2.36e-02	59
GO:0050808	Colorectum	AD	synapse organization	112/3918	426/18723	4.25e-03	2.92e-02	112
GO:0099003	Colorectum	AD	vesicle-mediated transport in synapse	57/3918	200/18723	6.53e-03	4.06e-02	57
GO:0032411	Colorectum	AD	positive regulation of transporter activity	37/3918	120/18723	6.82e-03	4.22e-02	37
GO:00726591	Colorectum	SER	protein localization to plasma membrane	92/2897	284/18723	6.36e-13	1.86e-10	92
GO:19907781	Colorectum	SER	protein localization to cell periphery	98/2897	333/18723	6.09e-11	9.57e-09	98
GO:00300481	Colorectum	SER	actin filament-based movement	38/2897	127/18723	2.80e-05	7.56e-04	38
GO:00602491	Colorectum	SER	anatomical structure homeostasis	74/2897	314/18723	1.01e-04	2.13e-03	74
GO:00459211	Colorectum	SER	positive regulation of exocytosis	25/2897	86/18723	9.88e-04	1.17e-02	25
GO:00068871	Colorectum	SER	exocytosis	75/2897	352/18723	2.05e-03	2.03e-02	75
GO:00324111	Colorectum	SER	positive regulation of transporter activity	31/2897	120/18723	2.25e-03	2.16e-02	31
GO:0003012	Colorectum	SER	muscle system process	92/2897	452/18723	2.98e-03	2.63e-02	92

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa042602	Colorectum	SER	Cardiac muscle contraction	31/1580	87/8465	1.30e-04	1.30e-03	9.47e-04	31
hsa042603	Colorectum	SER	Cardiac muscle contraction	31/1580	87/8465	1.30e-04	1.30e-03	9.47e-04	31
hsa042604	Colorectum	MSS	Cardiac muscle contraction	31/1875	87/8465	2.73e-03	1.32e-02	8.12e-03	31
hsa042605	Colorectum	MSS	Cardiac muscle contraction	31/1875	87/8465	2.73e-03	1.32e-02	8.12e-03	31
hsa05412	Colorectum	FAP	Arrhythmogenic right ventricular cardiomyopathy	23/1404	77/8465	2.58e-03	1.19e-02	7.23e-03	23
hsa04010	Colorectum	FAP	MAPK signaling pathway	68/1404	302/8465	4.00e-03	1.67e-02	1.02e-02	68
hsa04261	Colorectum	FAP	Adrenergic signaling in cardiomyocytes	38/1404	154/8465	6.16e-03	2.34e-02	1.42e-02	38
hsa042608	Colorectum	FAP	Cardiac muscle contraction	24/1404	87/8465	6.49e-03	2.43e-02	1.48e-02	24
hsa054121	Colorectum	FAP	Arrhythmogenic right ventricular cardiomyopathy	23/1404	77/8465	2.58e-03	1.19e-02	7.23e-03	23
hsa040101	Colorectum	FAP	MAPK signaling pathway	68/1404	302/8465	4.00e-03	1.67e-02	1.02e-02	68
hsa042611	Colorectum	FAP	Adrenergic signaling in cardiomyocytes	38/1404	154/8465	6.16e-03	2.34e-02	1.42e-02	38
hsa042609	Colorectum	FAP	Cardiac muscle contraction	24/1404	87/8465	6.49e-03	2.43e-02	1.48e-02	24
hsa040102	Colorectum	CRC	MAPK signaling pathway	56/1091	302/8465	2.76e-03	1.77e-02	1.20e-02	56
hsa042612	Colorectum	CRC	Adrenergic signaling in cardiomyocytes	32/1091	154/8465	3.81e-03	2.31e-02	1.57e-02	32
hsa040103	Colorectum	CRC	MAPK signaling pathway	56/1091	302/8465	2.76e-03	1.77e-02	1.20e-02	56
hsa042613	Colorectum	CRC	Adrenergic signaling in cardiomyocytes	32/1091	154/8465	3.81e-03	2.31e-02	1.57e-02	32

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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

CACNB2

SNV

Missense_Mutation

c.1079N>T

p.Arg360Met

p.R360M

Q08289

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CACNB2

SNV

Missense_Mutation

c.1545N>T

p.Gln515His

p.Q515H

Q08289

protein_coding

tolerated(0.44)

benign(0.001)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

CACNB2

SNV

Missense_Mutation

rs368719191

c.427N>A

p.Glu143Lys

p.E143K

Q08289

protein_coding

tolerated(0.1)

benign(0.375)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CACNB2

insertion

In_Frame_Ins

novel

c.1870_1871insCATCTGTATTTG

p.Gln624delinsProSerValPheGlu

p.Q624delinsPSVFE

Q08289

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

CACNB2

deletion

Frame_Shift_Del

novel

c.1712delA

p.Lys571ArgfsTer71

p.K571Rfs*71

Q08289

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CACNB2

deletion

Frame_Shift_Del

c.902_908delAAAAAGC

p.Gln301ArgfsTer6

p.Q301Rfs*6

Q08289

protein_coding

TCGA-EW-A1PB-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CACNB2

SNV

Missense_Mutation

novel

c.1495C>G

p.Gln499Glu

p.Q499E

Q08289

protein_coding

tolerated(0.24)

benign(0.03)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CACNB2

SNV

Missense_Mutation

rs781454884

c.1829N>A

p.Arg610Gln

p.R610Q

Q08289

protein_coding

tolerated_low_confidence(0.43)

benign(0.079)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

CACNB2

SNV

Missense_Mutation

rs771011929

c.1823N>A

p.Arg608His

p.R608H

Q08289

protein_coding

tolerated_low_confidence(0.1)

probably_damaging(0.996)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

CACNB2

SNV

Missense_Mutation

rs758934103

c.1880G>A

p.Arg627His

p.R627H

Q08289

protein_coding

tolerated_low_confidence(0.18)

probably_damaging(0.992)

TCGA-AA-3877-01

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
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL		ARVERAPAMIL
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL		FELODIPINE	FELODIPINE
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL	modulator	CHEMBL940	GABAPENTIN
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL	blocker	CHEMBL1200382	BEPRIDIL HYDROCHLORIDE
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL		celecoxib	CELECOXIB	22336956
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL	modulator	CHEMBL593430	ATAGABALIN
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL		VERAPAMIL	VERAPAMIL
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL	modulator	CHEMBL2103836	IMAGABALIN
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL	modulator	CHEMBL1628502	GABAPENTIN ENACARBIL
783	CACNB2	DRUGGABLE GENOME, ION CHANNEL	modulator	CHEMBL1059	PREGABALIN

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