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: RER1

Gene summary for RER1

Gene summary.

Gene information	Species	Human
	Gene symbol	RER1
	Gene ID	11079
	Gene name	retention in endoplasmic reticulum sorting receptor 1
	Gene Alias	RER1
	Cytomap	1p36.32
	Gene Type	protein-coding
	GO ID	GO:0001941
	UniProtAcc	O15258

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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
11079	RER1	cSCC_p9	Human	Skin	cSCC	2.63e-06	1.31e-01	-0.1991
11079	RER1	male-WTA	Human	Thyroid	PTC	2.92e-41	3.43e-01	0.1037
11079	RER1	PTC01	Human	Thyroid	PTC	3.00e-22	5.74e-01	0.1899
11079	RER1	PTC03	Human	Thyroid	PTC	7.99e-04	4.44e-01	0.1784
11079	RER1	PTC04	Human	Thyroid	PTC	3.98e-21	5.73e-01	0.1927
11079	RER1	PTC05	Human	Thyroid	PTC	5.29e-27	1.15e+00	0.2065
11079	RER1	PTC06	Human	Thyroid	PTC	4.86e-51	1.41e+00	0.2057
11079	RER1	PTC07	Human	Thyroid	PTC	5.01e-74	1.33e+00	0.2044
11079	RER1	ATC08	Human	Thyroid	ATC	3.49e-05	1.46e-01	0.0541
11079	RER1	ATC09	Human	Thyroid	ATC	2.64e-10	7.33e-01	0.2871
11079	RER1	ATC11	Human	Thyroid	ATC	4.38e-05	6.48e-01	0.3386
11079	RER1	ATC12	Human	Thyroid	ATC	2.09e-31	7.75e-01	0.34
11079	RER1	ATC13	Human	Thyroid	ATC	1.05e-48	1.15e+00	0.34
11079	RER1	ATC1	Human	Thyroid	ATC	5.23e-10	8.02e-01	0.2878
11079	RER1	ATC2	Human	Thyroid	ATC	2.50e-22	2.14e+00	0.34
11079	RER1	ATC3	Human	Thyroid	ATC	3.04e-07	4.06e-01	0.338
11079	RER1	ATC4	Human	Thyroid	ATC	5.14e-33	1.01e+00	0.34
11079	RER1	ATC5	Human	Thyroid	ATC	4.05e-51	1.27e+00	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
GO:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:1903829	Colorectum	AD	positive regulation of cellular protein localization	110/3918	276/18723	4.58e-13	8.44e-11	110
GO:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:1905475	Colorectum	AD	regulation of protein localization to membrane	73/3918	175/18723	3.37e-10	2.93e-08	73
GO:1903076	Colorectum	AD	regulation of protein localization to plasma membrane	48/3918	104/18723	7.17e-09	4.36e-07	48
GO:1904375	Colorectum	AD	regulation of protein localization to cell periphery	54/3918	125/18723	1.52e-08	9.00e-07	54
GO:1905477	Colorectum	AD	positive regulation of protein localization to membrane	46/3918	106/18723	1.47e-07	6.64e-06	46
GO:0006890	Colorectum	AD	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	27/3918	52/18723	7.67e-07	2.70e-05	27
GO:1903078	Colorectum	AD	positive regulation of protein localization to plasma membrane	28/3918	62/18723	1.57e-05	3.34e-04	28
GO:1904377	Colorectum	AD	positive regulation of protein localization to cell periphery	30/3918	69/18723	1.98e-05	4.05e-04	30
GO:0032507	Colorectum	AD	maintenance of protein location in cell	25/3918	65/18723	9.12e-04	8.71e-03	25
GO:0099173	Colorectum	AD	postsynapse organization	51/3918	168/18723	2.47e-03	1.90e-02	51
GO:0070972	Colorectum	AD	protein localization to endoplasmic reticulum	26/3918	74/18723	3.28e-03	2.40e-02	26
GO:0050808	Colorectum	AD	synapse organization	112/3918	426/18723	4.25e-03	2.92e-02	112
GO:0051651	Colorectum	AD	maintenance of location in cell	61/3918	214/18723	5.02e-03	3.37e-02	61
GO:0045185	Colorectum	AD	maintenance of protein location	30/3918	94/18723	8.26e-03	4.85e-02	30
GO:00726591	Colorectum	SER	protein localization to plasma membrane	92/2897	284/18723	6.36e-13	1.86e-10	92
GO:19038291	Colorectum	SER	positive regulation of cellular protein localization	86/2897	276/18723	3.61e-11	6.11e-09	86
GO:19907781	Colorectum	SER	protein localization to cell periphery	98/2897	333/18723	6.09e-11	9.57e-09	98

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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

RER1

SNV

Missense_Mutation

novel

c.58A>G

p.Arg20Gly

p.R20G

O15258

protein_coding

deleterious(0.04)

benign(0.122)

TCGA-AC-A23C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

chemo

RER1

insertion

Nonsense_Mutation

novel

c.359_360insCTG

p.Lys120delinsAsnTer

p.K120delinsN*

O15258

protein_coding

TCGA-AN-A0FJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RER1

insertion

Frame_Shift_Ins

novel

c.361_362insGGTTGCTCTGCCTTACAGATGACGGTCC

p.Phe121TrpfsTer60

p.F121Wfs*60

O15258

protein_coding

TCGA-AN-A0FJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RER1

deletion

Frame_Shift_Del

novel

c.348_349delNN

p.Pro117ArgfsTer3

p.P117Rfs*3

O15258

protein_coding

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

RER1

SNV

Missense_Mutation

novel

c.464T>C

p.Ile155Thr

p.I155T

O15258

protein_coding

deleterious(0)

probably_damaging(0.915)

TCGA-CK-5913-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

RER1

SNV

Missense_Mutation

rs746542852

c.47C>T

p.Ser16Leu

p.S16L

O15258

protein_coding

tolerated(0.2)

probably_damaging(0.915)

TCGA-G4-6304-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

RER1

SNV

Missense_Mutation

novel

c.434N>C

p.Val145Ala

p.V145A

O15258

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

RER1

SNV

Missense_Mutation

novel

c.520T>C

p.Tyr174His

p.Y174H

O15258

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RER1

SNV

Missense_Mutation

rs567205815

c.583G>A

p.Ala195Thr

p.A195T

O15258

protein_coding

tolerated(0.15)

benign(0.001)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

RER1

SNV

Missense_Mutation

c.418G>A

p.Ala140Thr

p.A140T

O15258

protein_coding

deleterious(0.05)

benign(0.196)

TCGA-AP-A051-01

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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