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: SPOP

Gene summary for SPOP

Gene summary.

Gene information	Species	Human
	Gene symbol	SPOP
	Gene ID	8405
	Gene name	speckle type BTB/POZ protein
	Gene Alias	BTBD32
	Cytomap	17q21.33
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	O43791

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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
8405	SPOP	LZE4T	Human	Esophagus	ESCC	7.41e-13	4.52e-01	0.0811
8405	SPOP	LZE7T	Human	Esophagus	ESCC	1.13e-05	4.31e-01	0.0667
8405	SPOP	LZE8T	Human	Esophagus	ESCC	1.12e-11	2.43e-01	0.067
8405	SPOP	LZE24T	Human	Esophagus	ESCC	9.69e-22	7.00e-01	0.0596
8405	SPOP	P1T-E	Human	Esophagus	ESCC	6.19e-06	2.82e-01	0.0875
8405	SPOP	P2T-E	Human	Esophagus	ESCC	2.81e-35	5.80e-01	0.1177
8405	SPOP	P4T-E	Human	Esophagus	ESCC	1.29e-24	6.74e-01	0.1323
8405	SPOP	P5T-E	Human	Esophagus	ESCC	4.77e-13	3.31e-01	0.1327
8405	SPOP	P8T-E	Human	Esophagus	ESCC	1.81e-29	6.47e-01	0.0889
8405	SPOP	P9T-E	Human	Esophagus	ESCC	4.24e-10	2.05e-01	0.1131
8405	SPOP	P10T-E	Human	Esophagus	ESCC	5.69e-26	5.60e-01	0.116
8405	SPOP	P11T-E	Human	Esophagus	ESCC	1.40e-19	8.50e-01	0.1426
8405	SPOP	P12T-E	Human	Esophagus	ESCC	3.97e-33	7.15e-01	0.1122
8405	SPOP	P15T-E	Human	Esophagus	ESCC	3.27e-27	5.33e-01	0.1149
8405	SPOP	P16T-E	Human	Esophagus	ESCC	2.16e-22	5.79e-01	0.1153
8405	SPOP	P17T-E	Human	Esophagus	ESCC	1.16e-08	4.76e-01	0.1278
8405	SPOP	P19T-E	Human	Esophagus	ESCC	1.74e-08	6.12e-01	0.1662
8405	SPOP	P20T-E	Human	Esophagus	ESCC	2.56e-14	5.60e-01	0.1124
8405	SPOP	P21T-E	Human	Esophagus	ESCC	2.81e-24	6.28e-01	0.1617
8405	SPOP	P22T-E	Human	Esophagus	ESCC	1.34e-25	4.22e-01	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
GO:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:00002095	Liver	NAFLD	protein polyubiquitination	51/1882	236/18723	1.04e-07	8.10e-06	51
GO:001049812	Liver	Cirrhotic	proteasomal protein catabolic process	216/4634	490/18723	2.52e-21	9.29e-19	216
GO:004316112	Liver	Cirrhotic	proteasome-mediated ubiquitin-dependent protein catabolic process	184/4634	412/18723	4.52e-19	8.85e-17	184
GO:000020911	Liver	Cirrhotic	protein polyubiquitination	89/4634	236/18723	6.09e-06	9.80e-05	89
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351
GO:004316122	Liver	HCC	proteasome-mediated ubiquitin-dependent protein catabolic process	299/7958	412/18723	7.82e-36	8.27e-33	299
GO:000020921	Liver	HCC	protein polyubiquitination	151/7958	236/18723	1.90e-11	7.59e-10	151
GO:001049820	Oral cavity	OSCC	proteasomal protein catabolic process	336/7305	490/18723	5.45e-41	8.63e-38	336
GO:004316120	Oral cavity	OSCC	proteasome-mediated ubiquitin-dependent protein catabolic process	285/7305	412/18723	5.68e-36	5.99e-33	285
GO:000020910	Oral cavity	OSCC	protein polyubiquitination	150/7305	236/18723	1.59e-14	9.27e-13	150
GO:0010498110	Oral cavity	LP	proteasomal protein catabolic process	224/4623	490/18723	9.57e-25	4.00e-22	224
GO:0043161110	Oral cavity	LP	proteasome-mediated ubiquitin-dependent protein catabolic process	190/4623	412/18723	1.08e-21	2.93e-19	190
GO:000020915	Oral cavity	LP	protein polyubiquitination	82/4623	236/18723	3.23e-04	3.26e-03	82
GO:001049828	Skin	cSCC	proteasomal protein catabolic process	243/4864	490/18723	7.85e-30	4.10e-27	243
GO:004316128	Skin	cSCC	proteasome-mediated ubiquitin-dependent protein catabolic process	205/4864	412/18723	1.46e-25	4.16e-23	205

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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

SPOP

SNV

Missense_Mutation

novel

c.164N>G

p.Ser55Cys

p.S55C

O43791

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

SPOP

SNV

Missense_Mutation

c.973N>G

p.Ile325Val

p.I325V

O43791

protein_coding

deleterious(0.02)

benign(0.009)

TCGA-AO-A0JM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SPOP

SNV

Missense_Mutation

novel

c.662N>A

p.Arg221His

p.R221H

O43791

protein_coding

tolerated(0.07)

probably_damaging(1)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SPOP

SNV

Missense_Mutation

c.601N>C

p.Asp201His

p.D201H

O43791

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

SPOP

SNV

Missense_Mutation

c.418N>A

p.Asp140Asn

p.D140N

O43791

protein_coding

deleterious(0.02)

possibly_damaging(0.805)

TCGA-S3-AA11-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

SPOP

insertion

Nonsense_Mutation

novel

c.600_601insAAATGGAGTATGAGTCCCTAAACTCCTTCTGAGAGCAGAGAGAAGTGG

p.Thr200_Asp201insLysTrpSerMetSerProTerThrProSerGluSerArgGluLysTrp

p.T200_D201insKWSMSP*TPSESREKW

O43791

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

SPOP

insertion

Frame_Shift_Ins

novel

c.212_213insGGGTCCAGCCTTTTCTCATATGCTTCCCCCTCTC

p.Asn72GlyfsTer18

p.N72Gfs*18

O43791

protein_coding

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

SPOP

insertion

Frame_Shift_Ins

novel

c.586_587insGAGTTAGGAGGACTGTGGGAGA

p.Asn196ArgfsTer38

p.N196Rfs*38

O43791

protein_coding

TCGA-E9-A1NI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SPOP

SNV

Missense_Mutation

c.362N>A

p.Arg121Gln

p.R121Q

O43791

protein_coding

tolerated(0.17)

benign(0.015)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SPOP

SNV

Missense_Mutation

c.349A>G

p.Met117Val

p.M117V

O43791

protein_coding

tolerated(0.12)

benign(0.007)

TCGA-JW-A5VH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

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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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