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: MVP

Gene summary for MVP

Gene summary.

Gene information	Species	Human
	Gene symbol	MVP
	Gene ID	9961
	Gene name	major vault protein
	Gene Alias	LRP
	Cytomap	16p11.2
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q14764

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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
9961	MVP	HTA11_2487_2000001011	Human	Colorectum	SER	3.75e-18	1.00e+00	-0.1808
9961	MVP	HTA11_1938_2000001011	Human	Colorectum	AD	1.12e-10	7.19e-01	-0.0811
9961	MVP	HTA11_78_2000001011	Human	Colorectum	AD	3.25e-05	5.65e-01	-0.1088
9961	MVP	HTA11_347_2000001011	Human	Colorectum	AD	2.19e-24	8.62e-01	-0.1954
9961	MVP	HTA11_411_2000001011	Human	Colorectum	SER	2.63e-10	1.68e+00	-0.2602
9961	MVP	HTA11_2112_2000001011	Human	Colorectum	SER	1.55e-13	1.42e+00	-0.2196
9961	MVP	HTA11_3361_2000001011	Human	Colorectum	AD	3.76e-10	7.86e-01	-0.1207
9961	MVP	HTA11_83_2000001011	Human	Colorectum	SER	1.63e-08	7.91e-01	-0.1526
9961	MVP	HTA11_696_2000001011	Human	Colorectum	AD	1.67e-33	1.12e+00	-0.1464
9961	MVP	HTA11_866_2000001011	Human	Colorectum	AD	4.17e-12	6.22e-01	-0.1001
9961	MVP	HTA11_1391_2000001011	Human	Colorectum	AD	4.22e-20	1.05e+00	-0.059
9961	MVP	HTA11_2992_2000001011	Human	Colorectum	SER	1.36e-06	8.75e-01	-0.1706
9961	MVP	HTA11_5212_2000001011	Human	Colorectum	AD	1.01e-03	7.01e-01	-0.2061
9961	MVP	HTA11_5216_2000001011	Human	Colorectum	SER	1.33e-03	8.34e-01	-0.1462
9961	MVP	HTA11_546_2000001011	Human	Colorectum	AD	1.88e-05	6.84e-01	-0.0842
9961	MVP	HTA11_10711_2000001011	Human	Colorectum	AD	3.00e-02	4.10e-01	0.0338
9961	MVP	HTA11_7696_3000711011	Human	Colorectum	AD	2.43e-02	3.23e-01	0.0674
9961	MVP	HTA11_99999971662_82457	Human	Colorectum	MSS	1.93e-11	6.51e-01	0.3859
9961	MVP	F007	Human	Colorectum	FAP	1.89e-04	-3.42e-01	0.1176
9961	MVP	A002-C-010	Human	Colorectum	FAP	4.10e-05	-2.19e-01	0.242

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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
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
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:00420583	Colorectum	CRC	regulation of epidermal growth factor receptor signaling pathway	22/2078	73/18723	8.21e-06	2.96e-04	22
GO:19011843	Colorectum	CRC	regulation of ERBB signaling pathway	23/2078	79/18723	9.77e-06	3.31e-04	23
GO:19011854	Colorectum	CRC	negative regulation of ERBB signaling pathway	13/2078	32/18723	1.69e-05	5.16e-04	13
GO:00420593	Colorectum	CRC	negative regulation of epidermal growth factor receptor signaling pathway	12/2078	28/18723	1.87e-05	5.59e-04	12
GO:00513485	Colorectum	CRC	negative regulation of transferase activity	48/2078	268/18723	5.56e-04	7.70e-03	48
GO:00467774	Colorectum	CRC	protein autophosphorylation	42/2078	227/18723	6.08e-04	8.10e-03	42
GO:00064694	Colorectum	CRC	negative regulation of protein kinase activity	39/2078	212/18723	1.04e-03	1.22e-02	39
GO:00610993	Colorectum	CRC	negative regulation of protein tyrosine kinase activity	10/2078	31/18723	1.37e-03	1.50e-02	10
GO:00019335	Colorectum	CRC	negative regulation of protein phosphorylation	55/2078	342/18723	3.05e-03	2.72e-02	55
GO:00459365	Colorectum	CRC	negative regulation of phosphate metabolic process	68/2078	441/18723	3.15e-03	2.78e-02	68
GO:00105635	Colorectum	CRC	negative regulation of phosphorus metabolic process	68/2078	442/18723	3.33e-03	2.85e-02	68
GO:00336734	Colorectum	CRC	negative regulation of kinase activity	40/2078	237/18723	4.58e-03	3.57e-02	40
GO:00064035	Colorectum	CRC	RNA localization	35/2078	201/18723	4.64e-03	3.61e-02	35
GO:00423265	Colorectum	CRC	negative regulation of phosphorylation	59/2078	385/18723	6.45e-03	4.67e-02	59
GO:0006403110	Esophagus	ESCC	RNA localization	166/8552	201/18723	1.95e-27	6.18e-25	166
GO:005123617	Esophagus	ESCC	establishment of RNA localization	134/8552	166/18723	1.23e-20	1.81e-18	134
GO:005102815	Esophagus	ESCC	mRNA transport	110/8552	130/18723	2.76e-20	3.80e-18	110
GO:005065717	Esophagus	ESCC	nucleic acid transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:005065817	Esophagus	ESCC	RNA transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:001593117	Esophagus	ESCC	nucleobase-containing compound transport	162/8552	222/18723	9.87e-17	7.93e-15	162

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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

MVP

SNV

Missense_Mutation

c.510G>C

p.Gln170His

p.Q170H

Q14764

protein_coding

tolerated(0.29)

benign(0.003)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MVP

SNV

Missense_Mutation

c.1234G>A

p.Glu412Lys

p.E412K

Q14764

protein_coding

deleterious(0)

probably_damaging(0.952)

TCGA-C8-A3M7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MVP

insertion

Frame_Shift_Ins

novel

c.2374_2375insAAGGCCTTTTGCAATGGCTATTCCTGCTGCCCAGAAAGCT

p.Val792GlufsTer38

p.V792Efs*38

Q14764

protein_coding

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

MVP

insertion

Frame_Shift_Ins

novel

c.874_875insA

p.Gly292GlufsTer55

p.G292Efs*55

Q14764

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MVP

insertion

In_Frame_Ins

novel

c.875_876insCTCTTCCTTTGAGCCCCAGTTTCAGTT

p.Gly292_Lys293insSerSerPheGluProGlnPheGlnPhe

p.G292_K293insSSFEPQFQF

Q14764

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MVP

insertion

Frame_Shift_Ins

novel

c.2596_2597insAGGTGAGAGTTGGGGAAGGTGTGTTGGTTTCAGGA

p.Pro866GlnfsTer43

p.P866Qfs*43

Q14764

protein_coding

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

MVP

insertion

Frame_Shift_Ins

rs778534743

c.1744dupG

p.Ala582GlyfsTer9

p.A582Gfs*9

Q14764

protein_coding

TCGA-BH-A0HX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adrimycin

MVP

SNV

Missense_Mutation

novel

c.2012C>T

p.Ala671Val

p.A671V

Q14764

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MVP

SNV

Missense_Mutation

novel

c.10N>A

p.Glu4Lys

p.E4K

Q14764

protein_coding

tolerated(0.15)

benign(0.08)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MVP

SNV

Missense_Mutation

c.2641N>G

p.Gln881Glu

p.Q881E

Q14764

protein_coding

tolerated_low_confidence(0.21)

benign(0)

TCGA-Q1-A5R2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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