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: SAR1B

Gene summary for SAR1B

Gene summary.

Gene information	Species	Human
	Gene symbol	SAR1B
	Gene ID	51128
	Gene name	secretion associated Ras related GTPase 1B
	Gene Alias	ANDD
	Cytomap	5q31.1
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	Q9Y6B6

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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
51128	SAR1B	LZE2T	Human	Esophagus	ESCC	1.54e-02	5.26e-01	0.082
51128	SAR1B	LZE4T	Human	Esophagus	ESCC	9.05e-21	5.19e-01	0.0811
51128	SAR1B	LZE5T	Human	Esophagus	ESCC	1.60e-04	3.45e-01	0.0514
51128	SAR1B	LZE7T	Human	Esophagus	ESCC	2.58e-05	2.46e-01	0.0667
51128	SAR1B	LZE8T	Human	Esophagus	ESCC	8.18e-09	3.55e-01	0.067
51128	SAR1B	LZE20T	Human	Esophagus	ESCC	2.48e-09	2.49e-01	0.0662
51128	SAR1B	LZE22T	Human	Esophagus	ESCC	6.47e-06	5.26e-01	0.068
51128	SAR1B	LZE24T	Human	Esophagus	ESCC	1.92e-30	9.19e-01	0.0596
51128	SAR1B	LZE21T	Human	Esophagus	ESCC	1.79e-05	3.59e-01	0.0655
51128	SAR1B	LZE6T	Human	Esophagus	ESCC	2.75e-11	4.58e-01	0.0845
51128	SAR1B	P1T-E	Human	Esophagus	ESCC	1.31e-03	3.56e-01	0.0875
51128	SAR1B	P2T-E	Human	Esophagus	ESCC	9.28e-27	4.48e-01	0.1177
51128	SAR1B	P4T-E	Human	Esophagus	ESCC	2.28e-35	7.25e-01	0.1323
51128	SAR1B	P5T-E	Human	Esophagus	ESCC	1.34e-43	8.54e-01	0.1327
51128	SAR1B	P8T-E	Human	Esophagus	ESCC	2.09e-19	3.35e-01	0.0889
51128	SAR1B	P9T-E	Human	Esophagus	ESCC	5.54e-23	4.33e-01	0.1131
51128	SAR1B	P10T-E	Human	Esophagus	ESCC	5.62e-23	2.62e-01	0.116
51128	SAR1B	P11T-E	Human	Esophagus	ESCC	3.96e-17	5.98e-01	0.1426
51128	SAR1B	P12T-E	Human	Esophagus	ESCC	3.43e-29	5.08e-01	0.1122
51128	SAR1B	P15T-E	Human	Esophagus	ESCC	4.32e-40	8.62e-01	0.1149

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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
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:005165614	Prostate	Tumor	establishment of organelle localization	109/3246	390/18723	9.97e-08	2.67e-06	109
GO:001605012	Prostate	Tumor	vesicle organization	87/3246	300/18723	3.44e-07	7.71e-06	87
GO:005165014	Prostate	Tumor	establishment of vesicle localization	49/3246	161/18723	3.02e-05	3.62e-04	49
GO:001988219	Prostate	Tumor	antigen processing and presentation	35/3246	106/18723	6.46e-05	6.99e-04	35
GO:000247415	Prostate	Tumor	antigen processing and presentation of peptide antigen via MHC class I	14/3246	28/18723	7.53e-05	7.86e-04	14
GO:005164813	Prostate	Tumor	vesicle localization	51/3246	177/18723	1.03e-04	9.96e-04	51
GO:009011412	Prostate	Tumor	COPII-coated vesicle budding	14/3246	29/18723	1.22e-04	1.14e-03	14
GO:004800218	Prostate	Tumor	antigen processing and presentation of peptide antigen	23/3246	62/18723	1.62e-04	1.46e-03	23
GO:003252712	Prostate	Tumor	protein exit from endoplasmic reticulum	19/3246	48/18723	2.23e-04	1.90e-03	19
GO:000690113	Prostate	Tumor	vesicle coating	9/3246	17/18723	8.89e-04	5.93e-03	9
GO:007086111	Prostate	Tumor	regulation of protein exit from endoplasmic reticulum	12/3246	27/18723	9.52e-04	6.20e-03	12
GO:000690313	Prostate	Tumor	vesicle targeting	16/3246	45/18723	2.59e-03	1.43e-02	16
GO:004820712	Prostate	Tumor	vesicle targeting, rough ER to cis-Golgi	7/3246	13/18723	3.02e-03	1.61e-02	7
GO:004820812	Prostate	Tumor	COPII vesicle coating	7/3246	13/18723	3.02e-03	1.61e-02	7
GO:004819912	Prostate	Tumor	vesicle targeting, to, from or within Golgi	9/3246	21/18723	5.54e-03	2.61e-02	9
GO:0048193110	Skin	cSCC	Golgi vesicle transport	153/4864	296/18723	1.85e-21	3.41e-19	153
GO:005165624	Skin	cSCC	establishment of organelle localization	178/4864	390/18723	2.18e-17	2.32e-15	178
GO:0032386110	Skin	cSCC	regulation of intracellular transport	156/4864	337/18723	4.48e-16	3.96e-14	156
GO:003315724	Skin	cSCC	regulation of intracellular protein transport	115/4864	229/18723	2.74e-15	2.23e-13	115
GO:000688810	Skin	cSCC	endoplasmic reticulum to Golgi vesicle-mediated transport	73/4864	130/18723	2.60e-13	1.57e-11	73

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0513428	Esophagus	ESCC	Legionellosis	42/4205	57/8465	1.83e-04	6.90e-04	3.53e-04	42
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0513436	Esophagus	ESCC	Legionellosis	42/4205	57/8465	1.83e-04	6.90e-04	3.53e-04	42
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0513412	Liver	Cirrhotic	Legionellosis	28/2530	57/8465	1.71e-03	8.01e-03	4.94e-03	28
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0513413	Liver	Cirrhotic	Legionellosis	28/2530	57/8465	1.71e-03	8.01e-03	4.94e-03	28
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
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa0513425	Oral cavity	OSCC	Legionellosis	42/3704	57/8465	4.18e-06	2.15e-05	1.10e-05	42
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa05134111	Oral cavity	OSCC	Legionellosis	42/3704	57/8465	4.18e-06	2.15e-05	1.10e-05	42
hsa04141210	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0513426	Oral cavity	LP	Legionellosis	33/2418	57/8465	3.29e-06	3.23e-05	2.08e-05	33
hsa0414138	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0513435	Oral cavity	LP	Legionellosis	33/2418	57/8465	3.29e-06	3.23e-05	2.08e-05	33
hsa0414128	Prostate	BPH	Protein processing in endoplasmic reticulum	97/1718	174/8465	2.37e-25	1.30e-23	8.07e-24	97
hsa0513420	Prostate	BPH	Legionellosis	22/1718	57/8465	1.10e-03	4.99e-03	3.09e-03	22

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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

SAR1B

insertion

Frame_Shift_Ins

novel

c.486_487insC

p.Ile163HisfsTer17

p.I163Hfs*17

Q9Y6B6

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SAR1B

insertion

In_Frame_Ins

novel

c.485_486insGTCTCAACGTTCAGGCTTACTCAGAGATTTGATTGC

p.Ser162delinsArgSerGlnArgSerGlyLeuLeuArgAspLeuIleAla

p.S162delinsRSQRSGLLRDLIA

Q9Y6B6

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SAR1B

SNV

Missense_Mutation

c.413N>A

p.Arg138Lys

p.R138K

Q9Y6B6

protein_coding

tolerated(0.72)

benign(0)

TCGA-LP-A5U3-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SAR1B

SNV

Missense_Mutation

novel

c.301N>A

p.Asp101Asn

p.D101N

Q9Y6B6

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SAR1B

SNV

Missense_Mutation

novel

c.272C>A

p.Pro91His

p.P91H

Q9Y6B6

protein_coding

deleterious(0.05)

benign(0.243)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SAR1B

SNV

Missense_Mutation

c.316G>A

p.Glu106Lys

p.E106K

Q9Y6B6

protein_coding

tolerated(0.07)

benign(0.013)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

SAR1B

SNV

Missense_Mutation

novel

c.523N>T

p.Val175Phe

p.V175F

Q9Y6B6

protein_coding

deleterious(0)

possibly_damaging(0.908)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SAR1B

SNV

Missense_Mutation

rs376731426

c.209N>T

p.Thr70Met

p.T70M

Q9Y6B6

protein_coding

deleterious(0.04)

benign(0.302)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

SAR1B

SNV

Missense_Mutation

novel

c.264N>A

p.Asn88Lys

p.N88K

Q9Y6B6

protein_coding

deleterious(0.03)

benign(0.057)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

SAR1B

SNV

Missense_Mutation

c.226N>A

p.Leu76Met

p.L76M

Q9Y6B6

protein_coding

deleterious(0.03)

probably_damaging(0.996)

TCGA-B5-A11G-01

Endometrium

uterine corpus endometrioid carcinoma

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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