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: SSR2

Gene summary for SSR2

Gene summary.

Gene information	Species	Human
	Gene symbol	SSR2
	Gene ID	6746
	Gene name	signal sequence receptor subunit 2
	Gene Alias	HSD25
	Cytomap	1q22
	Gene Type	protein-coding
	GO ID	GO:0006605
	UniProtAcc	P43308

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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
6746	SSR2	CA_HPV_1	Human	Cervix	CC	3.55e-07	-2.09e-01	0.0264
6746	SSR2	CA_HPV_3	Human	Cervix	CC	1.82e-03	8.11e-03	0.0414
6746	SSR2	CCI_1	Human	Cervix	CC	4.53e-04	-5.87e-01	0.528
6746	SSR2	CCI_3	Human	Cervix	CC	1.03e-04	-5.42e-01	0.516
6746	SSR2	CCII_1	Human	Cervix	CC	1.71e-21	-7.82e-01	0.3249
6746	SSR2	sample3	Human	Cervix	CC	2.10e-06	-1.74e-01	0.1387
6746	SSR2	L1	Human	Cervix	CC	6.48e-05	-9.56e-02	0.0802
6746	SSR2	T3	Human	Cervix	CC	1.69e-06	-2.33e-01	0.1389
6746	SSR2	HTA11_3410_2000001011	Human	Colorectum	AD	1.74e-13	4.12e-01	0.0155
6746	SSR2	HTA11_2487_2000001011	Human	Colorectum	SER	1.69e-14	7.02e-01	-0.1808
6746	SSR2	HTA11_2951_2000001011	Human	Colorectum	AD	3.54e-07	6.01e-01	0.0216
6746	SSR2	HTA11_1938_2000001011	Human	Colorectum	AD	1.41e-15	7.01e-01	-0.0811
6746	SSR2	HTA11_78_2000001011	Human	Colorectum	AD	5.60e-03	2.89e-01	-0.1088
6746	SSR2	HTA11_347_2000001011	Human	Colorectum	AD	4.05e-22	6.03e-01	-0.1954
6746	SSR2	HTA11_411_2000001011	Human	Colorectum	SER	1.07e-10	1.04e+00	-0.2602
6746	SSR2	HTA11_2112_2000001011	Human	Colorectum	SER	2.84e-06	8.46e-01	-0.2196
6746	SSR2	HTA11_3361_2000001011	Human	Colorectum	AD	3.57e-11	6.19e-01	-0.1207
6746	SSR2	HTA11_83_2000001011	Human	Colorectum	SER	2.80e-12	6.46e-01	-0.1526
6746	SSR2	HTA11_696_2000001011	Human	Colorectum	AD	2.95e-33	8.93e-01	-0.1464
6746	SSR2	HTA11_866_2000001011	Human	Colorectum	AD	3.59e-11	5.42e-01	-0.1001

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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
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
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
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:0090150110	Esophagus	ESCC	establishment of protein localization to membrane	182/8552	260/18723	1.27e-15	8.19e-14	182
GO:00066124	Esophagus	ESCC	protein targeting to membrane	83/8552	131/18723	3.31e-05	2.73e-04	83
GO:00066057	Liver	Cirrhotic	protein targeting	148/4634	314/18723	3.86e-18	6.20e-16	148
GO:00901507	Liver	Cirrhotic	establishment of protein localization to membrane	123/4634	260/18723	1.85e-15	2.15e-13	123
GO:00066122	Liver	Cirrhotic	protein targeting to membrane	53/4634	131/18723	5.17e-05	5.95e-04	53
GO:00066132	Liver	Cirrhotic	cotranslational protein targeting to membrane	17/4634	31/18723	3.19e-04	2.77e-03	17
GO:000660512	Liver	HCC	protein targeting	219/7958	314/18723	7.74e-23	1.49e-20	219
GO:009015012	Liver	HCC	establishment of protein localization to membrane	168/7958	260/18723	4.07e-13	2.13e-11	168
GO:00066121	Liver	HCC	protein targeting to membrane	75/7958	131/18723	4.58e-04	3.04e-03	75
GO:00066131	Liver	HCC	cotranslational protein targeting to membrane	20/7958	31/18723	1.11e-02	4.09e-02	20
GO:009015021	Liver	Cyst	establishment of protein localization to membrane	18/496	260/18723	2.09e-04	7.84e-03	18
GO:000660522	Liver	Cyst	protein targeting	20/496	314/18723	2.88e-04	9.60e-03	20
GO:00066058	Lung	IAC	protein targeting	51/2061	314/18723	2.91e-03	2.61e-02	51
GO:00901508	Lung	IAC	establishment of protein localization to membrane	43/2061	260/18723	4.25e-03	3.39e-02	43
GO:000660513	Lung	AIS	protein targeting	49/1849	314/18723	8.56e-04	1.17e-02	49
GO:009015013	Lung	AIS	establishment of protein localization to membrane	42/1849	260/18723	9.73e-04	1.28e-02	42
GO:000660520	Oral cavity	OSCC	protein targeting	204/7305	314/18723	6.78e-21	1.13e-18	204
GO:009015018	Oral cavity	OSCC	establishment of protein localization to membrane	163/7305	260/18723	7.13e-15	4.47e-13	163
GO:00066123	Oral cavity	OSCC	protein targeting to membrane	75/7305	131/18723	1.72e-05	1.69e-04	75
GO:0006605110	Oral cavity	LP	protein targeting	156/4623	314/18723	5.43e-22	1.62e-19	156

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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
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
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
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
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

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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

SSR2

SNV

Missense_Mutation

c.309C>G

p.Phe103Leu

p.F103L

P43308

protein_coding

tolerated(0.05)

possibly_damaging(0.519)

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SSR2

SNV

Missense_Mutation

c.337N>A

p.Leu113Met

p.L113M

P43308

protein_coding

tolerated(0.24)

benign(0.053)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

SSR2

SNV

Missense_Mutation

novel

c.31C>G

p.Leu11Val

p.L11V

P43308

protein_coding

tolerated(0.41)

benign(0.001)

TCGA-LL-A5YM-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unspecific

letrozole

SSR2

SNV

Missense_Mutation

c.113G>A

p.Arg38Gln

p.R38Q

P43308

protein_coding

tolerated(0.1)

benign(0.266)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SSR2

SNV

Missense_Mutation

c.81N>C

p.Lys27Asn

p.K27N

P43308

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

SSR2

SNV

Missense_Mutation

novel

c.28N>A

p.Ala10Thr

p.A10T

P43308

protein_coding

tolerated(0.08)

benign(0)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SSR2

SNV

Missense_Mutation

rs773535812

c.539N>T

p.Thr180Met

p.T180M

P43308

protein_coding

deleterious(0.03)

possibly_damaging(0.594)

TCGA-AP-A5FX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

SSR2

SNV

Missense_Mutation

rs143494097

c.169G>A

p.Val57Met

p.V57M

P43308

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

SSR2

SNV

Missense_Mutation

rs756957158

c.425N>A

p.Arg142Gln

p.R142Q

P43308

protein_coding

tolerated(0.19)

benign(0.143)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

SSR2

SNV

Missense_Mutation

rs756957158

c.425N>A

p.Arg142Gln

p.R142Q

P43308

protein_coding

tolerated(0.19)

benign(0.143)

TCGA-BK-A6W3-01

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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