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: CBLB

Gene summary for CBLB

Gene summary.

Gene information	Species	Human
	Gene symbol	CBLB
	Gene ID	868
	Gene name	Cbl proto-oncogene B
	Gene Alias	Cbl-b
	Cytomap	3q13.11
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q13191

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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
868	CBLB	CCI_2	Human	Cervix	CC	1.59e-04	7.81e-01	0.5249
868	CBLB	CCI_3	Human	Cervix	CC	6.32e-16	9.84e-01	0.516
868	CBLB	HTA11_5212_2000001011	Human	Colorectum	AD	5.04e-03	-6.00e-01	-0.2061
868	CBLB	HTA11_866_3004761011	Human	Colorectum	AD	1.65e-03	-3.32e-01	0.096
868	CBLB	HTA11_8622_2000001021	Human	Colorectum	SER	3.64e-02	-4.91e-01	0.0528
868	CBLB	HTA11_99999974143_84620	Human	Colorectum	MSS	4.40e-23	-6.20e-01	0.3005
868	CBLB	A002-C-010	Human	Colorectum	FAP	2.20e-03	1.31e-01	0.242
868	CBLB	A001-C-207	Human	Colorectum	FAP	8.74e-04	1.41e-01	0.1278
868	CBLB	A015-C-203	Human	Colorectum	FAP	1.50e-27	-2.52e-01	-0.1294
868	CBLB	A015-C-204	Human	Colorectum	FAP	1.34e-06	-2.13e-01	-0.0228
868	CBLB	A014-C-040	Human	Colorectum	FAP	5.84e-05	-2.28e-01	-0.1184
868	CBLB	A002-C-201	Human	Colorectum	FAP	3.42e-14	-2.35e-01	0.0324
868	CBLB	A002-C-203	Human	Colorectum	FAP	3.45e-03	-1.10e-03	0.2786
868	CBLB	A001-C-119	Human	Colorectum	FAP	6.83e-07	-4.03e-01	-0.1557
868	CBLB	A001-C-108	Human	Colorectum	FAP	4.53e-16	-2.54e-01	-0.0272
868	CBLB	A002-C-021	Human	Colorectum	FAP	4.58e-03	3.65e-01	0.1171
868	CBLB	A002-C-205	Human	Colorectum	FAP	7.28e-25	-3.41e-01	-0.1236
868	CBLB	A001-C-104	Human	Colorectum	FAP	1.95e-02	-7.98e-02	0.0184
868	CBLB	A015-C-006	Human	Colorectum	FAP	2.64e-18	-5.08e-01	-0.0994
868	CBLB	A015-C-106	Human	Colorectum	FAP	1.13e-10	-2.41e-01	-0.0511

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:003450421	Liver	HCC	protein localization to nucleus	194/7958	290/18723	2.84e-17	2.85e-15	194
GO:190332022	Liver	HCC	regulation of protein modification by small protein conjugation or removal	167/7958	242/18723	4.99e-17	4.72e-15	167
GO:005109822	Liver	HCC	regulation of binding	225/7958	363/18723	3.78e-14	2.37e-12	225
GO:001703811	Liver	HCC	protein import	140/7958	206/18723	1.12e-13	6.46e-12	140
GO:003139622	Liver	HCC	regulation of protein ubiquitination	142/7958	210/18723	1.39e-13	7.81e-12	142
GO:001056322	Liver	HCC	negative regulation of phosphorus metabolic process	259/7958	442/18723	4.29e-12	1.92e-10	259
GO:004593622	Liver	HCC	negative regulation of phosphate metabolic process	258/7958	441/18723	6.00e-12	2.60e-10	258
GO:004339322	Liver	HCC	regulation of protein binding	129/7958	196/18723	3.27e-11	1.26e-09	129
GO:004232622	Liver	HCC	negative regulation of phosphorylation	227/7958	385/18723	3.98e-11	1.52e-09	227
GO:005134822	Liver	HCC	negative regulation of transferase activity	166/7958	268/18723	8.97e-11	3.18e-09	166
GO:19033221	Liver	HCC	positive regulation of protein modification by small protein conjugation or removal	94/7958	138/18723	9.87e-10	3.01e-08	94
GO:003367322	Liver	HCC	negative regulation of kinase activity	144/7958	237/18723	9.76e-09	2.45e-07	144
GO:000193322	Liver	HCC	negative regulation of protein phosphorylation	196/7958	342/18723	1.95e-08	4.63e-07	196
GO:005117011	Liver	HCC	import into nucleus	102/7958	159/18723	2.78e-08	6.39e-07	102
GO:00066066	Liver	HCC	protein import into nucleus	99/7958	155/18723	6.12e-08	1.28e-06	99
GO:00313981	Liver	HCC	positive regulation of protein ubiquitination	79/7958	119/18723	1.18e-07	2.26e-06	79
GO:000646912	Liver	HCC	negative regulation of protein kinase activity	126/7958	212/18723	4.55e-07	7.49e-06	126
GO:003812721	Liver	HCC	ERBB signaling pathway	73/7958	121/18723	5.65e-05	5.26e-04	73
GO:000717321	Liver	HCC	epidermal growth factor receptor signaling pathway	65/7958	108/18723	1.56e-04	1.25e-03	65
GO:190118521	Liver	HCC	negative regulation of ERBB signaling pathway	23/7958	32/18723	7.37e-04	4.47e-03	23

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414418	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0401210	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa046254	Cervix	CC	C-type lectin receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa046604	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414419	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0401213	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa0462511	Cervix	CC	C-type lectin receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa0466011	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa04012	Colorectum	AD	ErbB signaling pathway	31/2092	85/8465	1.02e-02	3.91e-02	2.50e-02	31
hsa040121	Colorectum	AD	ErbB signaling pathway	31/2092	85/8465	1.02e-02	3.91e-02	2.50e-02	31
hsa041442	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041443	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041444	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa040122	Colorectum	MSS	ErbB signaling pathway	30/1875	85/8465	3.73e-03	1.67e-02	1.02e-02	30
hsa041445	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102

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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

CBLB

SNV

Missense_Mutation

c.422G>A

p.Arg141Gln

p.R141Q

Q13191

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CBLB

SNV

Missense_Mutation

c.1753N>A

p.Asp585Asn

p.D585N

Q13191

protein_coding

tolerated_low_confidence(0.06)

benign(0.001)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

CBLB

SNV

Missense_Mutation

rs748390313

c.2200N>T

p.Arg734Trp

p.R734W

Q13191

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.936)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CBLB

SNV

Missense_Mutation

novel

c.68N>G

p.Leu23Trp

p.L23W

Q13191

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.994)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CBLB

SNV

Missense_Mutation

c.229N>G

p.Ile77Val

p.I77V

Q13191

protein_coding

deleterious(0.02)

possibly_damaging(0.876)

TCGA-AO-A03L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

CBLB

SNV

Missense_Mutation

c.769C>T

p.His257Tyr

p.H257Y

Q13191

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CBLB

SNV

Missense_Mutation

c.952N>G

p.Gln318Glu

p.Q318E

Q13191

protein_coding

deleterious(0)

possibly_damaging(0.833)

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CBLB

SNV

Missense_Mutation

c.1210G>A

p.Asp404Asn

p.D404N

Q13191

protein_coding

deleterious(0.04)

probably_damaging(0.95)

TCGA-BH-A0B5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CBLB

SNV

Missense_Mutation

c.2483C>T

p.Ala828Val

p.A828V

Q13191

protein_coding

tolerated_low_confidence(0.4)

benign(0.116)

TCGA-BH-A0C1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CBLB

SNV

Missense_Mutation

c.1073N>G

p.Glu358Gly

p.E358G

Q13191

protein_coding

deleterious(0)

benign(0.241)

TCGA-BH-A0DK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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
868	CBLB	CLINICALLY ACTIONABLE, ENZYME		Fasudil	FASUDIL	26177294
868	CBLB	CLINICALLY ACTIONABLE, ENZYME		Fluorouracil	FLUOROURACIL	24351824

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