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: NPLOC4

Gene summary for NPLOC4

Gene summary.

Gene information	Species	Human
	Gene symbol	NPLOC4
	Gene ID	55666
	Gene name	NPL4 homolog, ubiquitin recognition factor
	Gene Alias	NPL4
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	A0A024R8R4

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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
55666	NPLOC4	CCI_1	Human	Cervix	CC	3.24e-04	6.65e-01	0.528
55666	NPLOC4	CCI_3	Human	Cervix	CC	1.47e-12	8.32e-01	0.516
55666	NPLOC4	sample3	Human	Cervix	CC	2.62e-04	2.04e-01	0.1387
55666	NPLOC4	T3	Human	Cervix	CC	4.09e-07	2.27e-01	0.1389
55666	NPLOC4	AEH-subject1	Human	Endometrium	AEH	2.68e-06	2.50e-01	-0.3059
55666	NPLOC4	AEH-subject4	Human	Endometrium	AEH	1.39e-04	2.58e-01	-0.2657
55666	NPLOC4	EEC-subject1	Human	Endometrium	EEC	1.66e-03	2.37e-01	-0.2682
55666	NPLOC4	EEC-subject3	Human	Endometrium	EEC	4.18e-02	8.91e-02	-0.2525
55666	NPLOC4	EEC-subject5	Human	Endometrium	EEC	4.00e-09	3.46e-01	-0.249
55666	NPLOC4	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	6.41e-03	-1.24e-04	-0.1869
55666	NPLOC4	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	7.31e-05	1.34e-02	-0.1934
55666	NPLOC4	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	4.95e-07	-2.07e-03	-0.1917
55666	NPLOC4	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	6.59e-05	-3.77e-02	-0.1916
55666	NPLOC4	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	3.50e-09	3.80e-01	-0.1269
55666	NPLOC4	LZE2T	Human	Esophagus	ESCC	1.86e-02	4.33e-01	0.082
55666	NPLOC4	LZE7T	Human	Esophagus	ESCC	2.05e-08	4.39e-01	0.0667
55666	NPLOC4	LZE20T	Human	Esophagus	ESCC	1.25e-02	1.05e-01	0.0662
55666	NPLOC4	LZE22T	Human	Esophagus	ESCC	3.08e-06	3.07e-01	0.068
55666	NPLOC4	LZE24T	Human	Esophagus	ESCC	2.49e-08	2.61e-01	0.0596
55666	NPLOC4	LZE21T	Human	Esophagus	ESCC	2.40e-02	1.72e-01	0.0655

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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
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:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:00026837	Cervix	CC	negative regulation of immune system process	94/2311	434/18723	2.63e-08	1.87e-06	94
GO:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00305229	Cervix	CC	intracellular receptor signaling pathway	60/2311	265/18723	1.89e-06	5.97e-05	60
GO:003497610	Cervix	CC	response to endoplasmic reticulum stress	57/2311	256/18723	5.81e-06	1.42e-04	57
GO:00028315	Cervix	CC	regulation of response to biotic stimulus	67/2311	327/18723	1.79e-05	3.36e-04	67
GO:00096158	Cervix	CC	response to virus	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:00022212	Cervix	CC	pattern recognition receptor signaling pathway	39/2311	172/18723	1.08e-04	1.38e-03	39
GO:00622073	Cervix	CC	regulation of pattern recognition receptor signaling pathway	27/2311	105/18723	1.37e-04	1.68e-03	27
GO:00027534	Cervix	CC	cytoplasmic pattern recognition receptor signaling pathway	18/2311	60/18723	2.26e-04	2.55e-03	18
GO:00028322	Cervix	CC	negative regulation of response to biotic stimulus	27/2311	108/18723	2.27e-04	2.55e-03	27
GO:00507773	Cervix	CC	negative regulation of immune response	41/2311	194/18723	3.63e-04	3.76e-03	41
GO:00321022	Cervix	CC	negative regulation of response to external stimulus	75/2311	420/18723	5.96e-04	5.61e-03	75
GO:00395292	Cervix	CC	RIG-I signaling pathway	10/2311	27/18723	9.25e-04	7.84e-03	10
GO:00395352	Cervix	CC	regulation of RIG-I signaling pathway	8/2311	20/18723	1.69e-03	1.29e-02	8
GO:0031348	Cervix	CC	negative regulation of defense response	48/2311	258/18723	2.30e-03	1.65e-02	48
GO:00985863	Cervix	CC	cellular response to virus	20/2311	84/18723	2.62e-03	1.81e-02	20
GO:00070304	Cervix	CC	Golgi organization	32/2311	157/18723	2.78e-03	1.87e-02	32
GO:00324791	Cervix	CC	regulation of type I interferon production	21/2311	95/18723	5.32e-03	3.10e-02	21

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414116	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0414117	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0414123	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35
hsa0414133	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141210	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0414138	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113

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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

NPLOC4

SNV

Missense_Mutation

novel

c.1536C>A

p.Phe512Leu

p.F512L

Q8TAT6

protein_coding

deleterious(0.03)

benign(0.389)

TCGA-A2-A3XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

NPLOC4

SNV

Missense_Mutation

novel

c.974T>C

p.Val325Ala

p.V325A

Q8TAT6

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

NPLOC4

insertion

Frame_Shift_Ins

novel

c.497_498insTATTATTTTAC

p.Tyr167IlefsTer9

p.Y167Ifs*9

Q8TAT6

protein_coding

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NPLOC4

insertion

Frame_Shift_Ins

novel

c.495_496insACCCTACCAGAAAGTAGCAGGCTTCA

p.Ala166ThrfsTer15

p.A166Tfs*15

Q8TAT6

protein_coding

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NPLOC4

insertion

Frame_Shift_Ins

novel

c.1415_1416insATTTCTATTTCGCAAAATCCATTTCC

p.Ile473PhefsTer129

p.I473Ffs*129

Q8TAT6

protein_coding

TCGA-AR-A2LR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NPLOC4

deletion

Frame_Shift_Del

novel

c.936delT

p.Phe312LeufsTer25

p.F312Lfs*25

Q8TAT6

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

NPLOC4

SNV

Missense_Mutation

novel

c.442N>A

p.Asp148Asn

p.D148N

Q8TAT6

protein_coding

deleterious(0.05)

possibly_damaging(0.518)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NPLOC4

SNV

Missense_Mutation

novel

c.397N>A

p.Gly133Ser

p.G133S

Q8TAT6

protein_coding

tolerated(0.06)

benign(0.209)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NPLOC4

SNV

Missense_Mutation

novel

c.962G>A

p.Arg321Gln

p.R321Q

Q8TAT6

protein_coding

tolerated(0.51)

benign(0.045)

TCGA-C5-A7CK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NPLOC4

SNV

Missense_Mutation

novel

c.1762N>T

p.His588Tyr

p.H588Y

Q8TAT6

protein_coding

deleterious(0.03)

possibly_damaging(0.854)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

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

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