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: SPSB3

Gene summary for SPSB3

Gene summary.

Gene information	Species	Human
	Gene symbol	SPSB3
	Gene ID	90864
	Gene name	splA/ryanodine receptor domain and SOCS box containing 3
	Gene Alias	C16orf31
	Cytomap	16p13.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q6PJ21

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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
90864	SPSB3	LZE4T	Human	Esophagus	ESCC	8.90e-17	3.34e-01	0.0811
90864	SPSB3	LZE7T	Human	Esophagus	ESCC	2.13e-18	1.12e+00	0.0667
90864	SPSB3	LZE8T	Human	Esophagus	ESCC	1.90e-14	4.21e-01	0.067
90864	SPSB3	LZE20T	Human	Esophagus	ESCC	5.90e-14	5.55e-01	0.0662
90864	SPSB3	LZE22D1	Human	Esophagus	HGIN	3.44e-06	5.94e-01	0.0595
90864	SPSB3	LZE22T	Human	Esophagus	ESCC	1.09e-04	7.57e-01	0.068
90864	SPSB3	LZE24T	Human	Esophagus	ESCC	5.48e-35	1.14e+00	0.0596
90864	SPSB3	LZE21T	Human	Esophagus	ESCC	3.25e-04	3.94e-01	0.0655
90864	SPSB3	LZE6T	Human	Esophagus	ESCC	1.59e-07	2.79e-01	0.0845
90864	SPSB3	P1T-E	Human	Esophagus	ESCC	8.74e-25	1.21e+00	0.0875
90864	SPSB3	P2T-E	Human	Esophagus	ESCC	1.07e-66	1.20e+00	0.1177
90864	SPSB3	P4T-E	Human	Esophagus	ESCC	4.60e-35	8.79e-01	0.1323
90864	SPSB3	P5T-E	Human	Esophagus	ESCC	3.58e-18	3.05e-01	0.1327
90864	SPSB3	P8T-E	Human	Esophagus	ESCC	6.68e-53	9.60e-01	0.0889
90864	SPSB3	P9T-E	Human	Esophagus	ESCC	8.73e-14	3.80e-01	0.1131
90864	SPSB3	P10T-E	Human	Esophagus	ESCC	1.97e-34	6.91e-01	0.116
90864	SPSB3	P11T-E	Human	Esophagus	ESCC	5.16e-25	9.67e-01	0.1426
90864	SPSB3	P12T-E	Human	Esophagus	ESCC	1.37e-59	1.26e+00	0.1122
90864	SPSB3	P15T-E	Human	Esophagus	ESCC	2.88e-38	8.47e-01	0.1149
90864	SPSB3	P16T-E	Human	Esophagus	ESCC	5.25e-28	5.55e-01	0.1153

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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:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
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: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: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: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: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: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
GO:0010498113	Thyroid	PTC	proteasomal protein catabolic process	297/5968	490/18723	4.58e-40	9.63e-37	297
GO:0043161113	Thyroid	PTC	proteasome-mediated ubiquitin-dependent protein catabolic process	254/5968	412/18723	3.91e-36	4.54e-33	254
GO:001049832	Thyroid	ATC	proteasomal protein catabolic process	309/6293	490/18723	1.78e-41	1.13e-37	309
GO:0043161210	Thyroid	ATC	proteasome-mediated ubiquitin-dependent protein catabolic process	265/6293	412/18723	7.09e-38	1.49e-34	265

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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

SPSB3

SNV

Missense_Mutation

novel

c.992C>T

p.Pro331Leu

p.P331L

Q6PJ21

protein_coding

deleterious(0.03)

benign(0.003)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

SPSB3

SNV

Missense_Mutation

c.103T>A

p.Trp35Arg

p.W35R

Q6PJ21

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.997)

TCGA-AR-A24X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SPSB3

SNV

Missense_Mutation

rs767649831

c.637N>T

p.Arg213Trp

p.R213W

Q6PJ21

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-E9-A5UP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SPSB3

SNV

Missense_Mutation

novel

c.95N>A

p.Ser32Tyr

p.S32Y

Q6PJ21

protein_coding

deleterious_low_confidence(0.02)

benign(0.133)

TCGA-S3-AA11-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

SPSB3

SNV

Missense_Mutation

novel

c.74N>T

p.Arg25Leu

p.R25L

Q6PJ21

protein_coding

tolerated_low_confidence(0.23)

benign(0.253)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

SPSB3

SNV

Missense_Mutation

novel

c.391N>C

p.Tyr131His

p.Y131H

Q6PJ21

protein_coding

deleterious(0.04)

probably_damaging(0.999)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

SPSB3

SNV

Missense_Mutation

rs771186190

c.1034N>A

p.Arg345Gln

p.R345Q

Q6PJ21

protein_coding

tolerated_low_confidence(0.24)

benign(0.017)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SPSB3

SNV

Missense_Mutation

rs756665663

c.64G>A

p.Ala22Thr

p.A22T

Q6PJ21

protein_coding

tolerated_low_confidence(0.46)

benign(0.003)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SPSB3

SNV

Missense_Mutation

novel

c.560G>A

p.Gly187Asp

p.G187D

Q6PJ21

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AP-A1DR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

SPSB3

SNV

Missense_Mutation

rs530459268

c.269N>A

p.Arg90Gln

p.R90Q

Q6PJ21

protein_coding

tolerated(0.36)

benign(0.007)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

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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