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: UPF3B

Gene summary for UPF3B

Gene summary.

Gene information	Species	Human
	Gene symbol	UPF3B
	Gene ID	65109
	Gene name	UPF3B regulator of nonsense mediated mRNA decay
	Gene Alias	HUPF3B
	Cytomap	Xq24
	Gene Type	protein-coding
	GO ID	GO:0000184
	UniProtAcc	Q9BZI7

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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
65109	UPF3B	A015-C-203	Human	Colorectum	FAP	7.07e-09	5.93e-02	-0.1294
65109	UPF3B	A002-C-201	Human	Colorectum	FAP	2.39e-02	7.47e-02	0.0324
65109	UPF3B	A001-C-119	Human	Colorectum	FAP	7.59e-07	5.20e-01	-0.1557
65109	UPF3B	A001-C-108	Human	Colorectum	FAP	1.58e-04	5.37e-02	-0.0272
65109	UPF3B	A002-C-205	Human	Colorectum	FAP	3.10e-07	1.62e-01	-0.1236
65109	UPF3B	A015-C-006	Human	Colorectum	FAP	3.36e-05	2.04e-01	-0.0994
65109	UPF3B	A002-C-114	Human	Colorectum	FAP	2.01e-03	-8.62e-02	-0.1561
65109	UPF3B	A015-C-104	Human	Colorectum	FAP	1.58e-10	5.23e-02	-0.1899
65109	UPF3B	A001-C-014	Human	Colorectum	FAP	3.64e-02	9.14e-02	0.0135
65109	UPF3B	A002-C-016	Human	Colorectum	FAP	9.09e-08	7.70e-04	0.0521
65109	UPF3B	A001-C-203	Human	Colorectum	FAP	4.03e-02	1.10e-01	-0.0481
65109	UPF3B	A002-C-116	Human	Colorectum	FAP	6.16e-13	-6.42e-03	-0.0452
65109	UPF3B	A014-C-008	Human	Colorectum	FAP	1.31e-02	-4.81e-02	-0.191
65109	UPF3B	A018-E-020	Human	Colorectum	FAP	3.55e-06	1.35e-01	-0.2034
65109	UPF3B	F034	Human	Colorectum	FAP	5.82e-08	1.67e-01	-0.0665
65109	UPF3B	LZE2T	Human	Esophagus	ESCC	4.48e-08	8.00e-01	0.082
65109	UPF3B	LZE4T	Human	Esophagus	ESCC	2.02e-05	3.19e-01	0.0811
65109	UPF3B	LZE7T	Human	Esophagus	ESCC	2.73e-17	1.17e+00	0.0667
65109	UPF3B	LZE20T	Human	Esophagus	ESCC	1.22e-09	3.16e-01	0.0662
65109	UPF3B	LZE24T	Human	Esophagus	ESCC	3.13e-37	1.14e+00	0.0596

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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
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:005116926	Thyroid	ATC	nuclear transport	180/6293	301/18723	6.97e-21	1.30e-18	180
GO:000640326	Thyroid	ATC	RNA localization	132/6293	201/18723	1.13e-20	1.93e-18	132
GO:000640127	Thyroid	ATC	RNA catabolic process	165/6293	278/18723	8.45e-19	1.14e-16	165
GO:000640227	Thyroid	ATC	mRNA catabolic process	140/6293	232/18723	5.08e-17	4.65e-15	140
GO:003465525	Thyroid	ATC	nucleobase-containing compound catabolic process	217/6293	407/18723	1.20e-16	1.04e-14	217
GO:000095624	Thyroid	ATC	nuclear-transcribed mRNA catabolic process	78/6293	112/18723	6.44e-15	4.07e-13	78
GO:004670024	Thyroid	ATC	heterocycle catabolic process	228/6293	445/18723	7.26e-15	4.50e-13	228
GO:004427025	Thyroid	ATC	cellular nitrogen compound catabolic process	229/6293	451/18723	2.25e-14	1.27e-12	229
GO:000641735	Thyroid	ATC	regulation of translation	236/6293	468/18723	2.39e-14	1.34e-12	236
GO:005123623	Thyroid	ATC	establishment of RNA localization	102/6293	166/18723	1.71e-13	8.60e-12	102
GO:001943924	Thyroid	ATC	aromatic compound catabolic process	232/6293	467/18723	3.05e-13	1.44e-11	232
GO:005065722	Thyroid	ATC	nucleic acid transport	100/6293	163/18723	3.39e-13	1.56e-11	100
GO:005065822	Thyroid	ATC	RNA transport	100/6293	163/18723	3.39e-13	1.56e-11	100
GO:004572733	Thyroid	ATC	positive regulation of translation	85/6293	136/18723	4.71e-12	1.84e-10	85
GO:003425034	Thyroid	ATC	positive regulation of cellular amide metabolic process	97/6293	162/18723	5.97e-12	2.30e-10	97
GO:190136124	Thyroid	ATC	organic cyclic compound catabolic process	238/6293	495/18723	1.12e-11	4.12e-10	238
GO:001593122	Thyroid	ATC	nucleobase-containing compound transport	122/6293	222/18723	4.30e-11	1.41e-09	122
GO:005102822	Thyroid	ATC	mRNA transport	80/6293	130/18723	6.13e-11	1.99e-09	80
GO:000018422	Thyroid	ATC	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	26/6293	37/18723	5.64e-06	6.00e-05	26

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa0301533	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa030133	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53

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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

UPF3B

SNV

Missense_Mutation

novel

c.1270N>A

p.Glu424Lys

p.E424K

Q9BZI7

protein_coding

tolerated(0.33)

benign(0.156)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

UPF3B

SNV

Missense_Mutation

c.1186N>C

p.Glu396Gln

p.E396Q

Q9BZI7

protein_coding

tolerated(0.11)

benign(0.11)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

UPF3B

SNV

Missense_Mutation

rs185347914

c.1049G>A

p.Arg350Gln

p.R350Q

Q9BZI7

protein_coding

deleterious(0.05)

benign(0.166)

TCGA-A7-A0CG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UPF3B

SNV

Missense_Mutation

c.994N>A

p.Glu332Lys

p.E332K

Q9BZI7

protein_coding

tolerated(0.11)

possibly_damaging(0.76)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UPF3B

SNV

Missense_Mutation

rs773491980

c.1082N>A

p.Arg361Gln

p.R361Q

Q9BZI7

protein_coding

tolerated(0.2)

benign(0.03)

TCGA-AN-A0AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UPF3B

SNV

Missense_Mutation

rs761031567

c.1135N>T

p.Arg379Cys

p.R379C

Q9BZI7

protein_coding

tolerated(0.07)

probably_damaging(0.913)

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

UPF3B

SNV

Missense_Mutation

novel

c.424G>C

p.Gly142Ala

p.G142A

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.992)

TCGA-AR-A1AS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

UPF3B

SNV

Missense_Mutation

c.1369N>A

p.Asp457Asn

p.D457N

Q9BZI7

protein_coding

tolerated(0.48)

benign(0.247)

TCGA-BH-A0EB-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

UPF3B

SNV

Missense_Mutation

rs373472438

c.1117N>T

p.Arg373Cys

p.R373C

Q9BZI7

protein_coding

deleterious(0.05)

benign(0.024)

TCGA-BH-A0HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

UPF3B

SNV

Missense_Mutation

c.1217N>C

p.Lys406Thr

p.K406T

Q9BZI7

protein_coding

deleterious(0.03)

benign(0.06)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

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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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