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: UPF2

Gene summary for UPF2

Gene summary.

Gene information	Species	Human
	Gene symbol	UPF2
	Gene ID	26019
	Gene name	UPF2 regulator of nonsense mediated mRNA decay
	Gene Alias	HUPF2
	Cytomap	10p14
	Gene Type	protein-coding
	GO ID	GO:0000184
	UniProtAcc	Q9HAU5

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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
26019	UPF2	HTA11_3410_2000001011	Human	Colorectum	AD	3.47e-09	-4.95e-01	0.0155
26019	UPF2	HTA11_696_2000001011	Human	Colorectum	AD	4.04e-02	-2.95e-01	-0.1464
26019	UPF2	HTA11_866_3004761011	Human	Colorectum	AD	1.35e-02	-4.01e-01	0.096
26019	UPF2	HTA11_99999974143_84620	Human	Colorectum	MSS	6.12e-08	-4.16e-01	0.3005
26019	UPF2	A002-C-010	Human	Colorectum	FAP	4.62e-05	-1.70e-01	0.242
26019	UPF2	A001-C-207	Human	Colorectum	FAP	1.32e-02	1.04e-01	0.1278
26019	UPF2	A015-C-203	Human	Colorectum	FAP	2.01e-36	3.24e-01	-0.1294
26019	UPF2	A015-C-204	Human	Colorectum	FAP	7.32e-08	3.22e-01	-0.0228
26019	UPF2	A014-C-040	Human	Colorectum	FAP	5.04e-07	4.18e-01	-0.1184
26019	UPF2	A002-C-201	Human	Colorectum	FAP	1.15e-09	5.92e-03	0.0324
26019	UPF2	A002-C-203	Human	Colorectum	FAP	9.50e-05	1.73e-02	0.2786
26019	UPF2	A001-C-119	Human	Colorectum	FAP	1.44e-13	4.35e-01	-0.1557
26019	UPF2	A001-C-108	Human	Colorectum	FAP	1.75e-27	4.13e-01	-0.0272
26019	UPF2	A002-C-021	Human	Colorectum	FAP	2.23e-05	4.12e-01	0.1171
26019	UPF2	A002-C-205	Human	Colorectum	FAP	3.54e-29	3.27e-01	-0.1236
26019	UPF2	A014-C-108	Human	Colorectum	FAP	7.42e-10	5.32e-01	-0.124
26019	UPF2	A001-C-104	Human	Colorectum	FAP	2.54e-12	3.55e-01	0.0184
26019	UPF2	A015-C-005	Human	Colorectum	FAP	7.72e-05	2.47e-01	-0.0336
26019	UPF2	A015-C-006	Human	Colorectum	FAP	6.78e-17	2.65e-01	-0.0994
26019	UPF2	A015-C-106	Human	Colorectum	FAP	3.54e-13	2.64e-01	-0.0511

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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
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:0048732	Colorectum	AD	gland development	149/3918	436/18723	6.07e-11	6.33e-09	149
GO:0006401	Colorectum	AD	RNA catabolic process	102/3918	278/18723	8.64e-10	6.76e-08	102
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0006402	Colorectum	AD	mRNA catabolic process	87/3918	232/18723	4.40e-09	2.84e-07	87
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0006913	Colorectum	AD	nucleocytoplasmic transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0051169	Colorectum	AD	nuclear transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0006403	Colorectum	AD	RNA localization	71/3918	201/18723	1.54e-06	4.76e-05	71
GO:0061008	Colorectum	AD	hepaticobiliary system development	55/3918	150/18723	6.34e-06	1.59e-04	55
GO:0001889	Colorectum	AD	liver development	54/3918	147/18723	7.20e-06	1.77e-04	54
GO:0051236	Colorectum	AD	establishment of RNA localization	58/3918	166/18723	1.95e-05	4.01e-04	58
GO:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:0050657	Colorectum	AD	nucleic acid transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0050658	Colorectum	AD	RNA transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0051168	Colorectum	AD	nuclear export	53/3918	154/18723	6.89e-05	1.11e-03	53
GO:0000956	Colorectum	AD	nuclear-transcribed mRNA catabolic process	40/3918	112/18723	2.11e-04	2.79e-03	40
GO:0051028	Colorectum	AD	mRNA transport	42/3918	130/18723	1.57e-03	1.32e-02	42

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030151	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030159	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa030137	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0301514	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75

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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

UPF2

SNV

Missense_Mutation

novel

c.1132G>A

p.Glu378Lys

p.E378K

Q9HAU5

protein_coding

deleterious(0.01)

possibly_damaging(0.76)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

UPF2

SNV

Missense_Mutation

c.1459G>C

p.Glu487Gln

p.E487Q

Q9HAU5

protein_coding

tolerated(0.12)

possibly_damaging(0.622)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UPF2

SNV

Missense_Mutation

c.3383N>A

p.Arg1128Gln

p.R1128Q

Q9HAU5

protein_coding

deleterious(0)

benign(0.097)

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UPF2

SNV

Missense_Mutation

rs772630723

c.2326C>T

p.Arg776Trp

p.R776W

Q9HAU5

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UPF2

SNV

Missense_Mutation

novel

c.277N>C

p.Glu93Gln

p.E93Q

Q9HAU5

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.932)

TCGA-B6-A0I2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UPF2

SNV

Missense_Mutation

novel

c.1159N>G

p.Ser387Ala

p.S387A

Q9HAU5

protein_coding

deleterious(0.02)

benign(0.09)

TCGA-C8-A278-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

UPF2

SNV

Missense_Mutation

c.3814N>T

p.Arg1272Cys

p.R1272C

Q9HAU5

protein_coding

deleterious_low_confidence(0)

benign(0.336)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UPF2

SNV

Missense_Mutation

c.309G>T

p.Lys103Asn

p.K103N

Q9HAU5

protein_coding

tolerated_low_confidence(0.1)

benign(0.048)

TCGA-E9-A1NE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

UPF2

SNV

Missense_Mutation

c.2536G>T

p.Val846Leu

p.V846L

Q9HAU5

protein_coding

tolerated(0.07)

possibly_damaging(0.857)

TCGA-EW-A1PB-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

UPF2

SNV

Missense_Mutation

c.2645G>A

p.Arg882Gln

p.R882Q

Q9HAU5

protein_coding

deleterious(0.04)

benign(0.216)

TCGA-2W-A8YY-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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