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: SSR4

Gene summary for SSR4

Gene summary.

Gene information	Species	Human
	Gene symbol	SSR4
	Gene ID	6748
	Gene name	signal sequence receptor subunit 4
	Gene Alias	CDG1Y
	Cytomap	Xq28
	Gene Type	protein-coding
	GO ID	GO:0005575
	UniProtAcc	P51571

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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
6748	SSR4	GSM4909277	Human	Breast	Precancer	6.13e-05	-8.60e-01	0.0177
6748	SSR4	GSM4909280	Human	Breast	Precancer	4.00e-05	-7.10e-01	0.0305
6748	SSR4	GSM4909282	Human	Breast	IDC	4.69e-06	2.55e-01	-0.0288
6748	SSR4	GSM4909287	Human	Breast	IDC	5.69e-30	4.42e-01	0.2057
6748	SSR4	GSM4909288	Human	Breast	IDC	4.10e-05	-2.39e-02	0.0988
6748	SSR4	GSM4909290	Human	Breast	IDC	9.51e-06	3.14e-01	0.2096
6748	SSR4	GSM4909293	Human	Breast	IDC	4.09e-07	-2.48e-01	0.1581
6748	SSR4	GSM4909294	Human	Breast	IDC	5.10e-18	-4.79e-02	0.2022
6748	SSR4	GSM4909296	Human	Breast	IDC	4.20e-23	1.21e-01	0.1524
6748	SSR4	GSM4909297	Human	Breast	IDC	3.86e-37	-2.68e-01	0.1517
6748	SSR4	GSM4909298	Human	Breast	IDC	3.12e-15	-4.14e-01	0.1551
6748	SSR4	GSM4909301	Human	Breast	IDC	3.70e-09	1.77e-01	0.1577
6748	SSR4	GSM4909302	Human	Breast	IDC	5.86e-14	2.53e-01	0.1545
6748	SSR4	GSM4909304	Human	Breast	IDC	7.74e-20	3.94e-01	0.1636
6748	SSR4	GSM4909306	Human	Breast	IDC	8.06e-05	2.52e-01	0.1564
6748	SSR4	GSM4909307	Human	Breast	IDC	1.56e-06	2.07e-01	0.1569
6748	SSR4	GSM4909308	Human	Breast	IDC	1.21e-10	3.78e-01	0.158
6748	SSR4	GSM4909309	Human	Breast	IDC	1.16e-03	-1.28e-01	0.0483
6748	SSR4	GSM4909311	Human	Breast	IDC	2.86e-68	-2.67e-01	0.1534
6748	SSR4	GSM4909312	Human	Breast	IDC	1.30e-18	-1.42e-01	0.1552

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
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
hsa0414144	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa0414154	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
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

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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

SSR4

SNV

Missense_Mutation

c.31G>T

p.Ala11Ser

p.A11S

P51571

protein_coding

tolerated(0.2)

benign(0.029)

TCGA-A1-A0SK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SSR4

SNV

Missense_Mutation

rs148637748

c.406G>A

p.Val136Met

p.V136M

P51571

protein_coding

tolerated(0.06)

probably_damaging(0.923)

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

SSR4

SNV

Missense_Mutation

novel

c.498N>G

p.Ser166Arg

p.S166R

P51571

protein_coding

deleterious(0)

benign(0.022)

TCGA-AC-A8OP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SSR4

SNV

Missense_Mutation

c.40C>G

p.Leu14Val

p.L14V

P51571

protein_coding

tolerated(0.94)

benign(0.038)

TCGA-DM-A28E-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SSR4

SNV

Missense_Mutation

novel

c.116N>A

p.Ser39Tyr

p.S39Y

P51571

protein_coding

deleterious(0)

possibly_damaging(0.897)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SSR4

SNV

Missense_Mutation

rs782018895

c.430G>A

p.Gly144Arg

p.G144R

P51571

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SSR4

SNV

Missense_Mutation

novel

c.5N>T

p.Ala2Val

p.A2V

P51571

protein_coding

tolerated_low_confidence(0.16)

benign(0)

TCGA-B5-A0JU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SSR4

SNV

Missense_Mutation

c.70N>A

p.Glu24Lys

p.E24K

P51571

protein_coding

tolerated(0.1)

benign(0.015)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

SSR4

SNV

Missense_Mutation

novel

c.318C>A

p.Phe106Leu

p.F106L

P51571

protein_coding

tolerated(0.52)

possibly_damaging(0.832)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SSR4

SNV

Missense_Mutation

novel

c.196N>G

p.Leu66Val

p.L66V

P51571

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-BG-A0RY-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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