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: SEC61A1

Gene summary for SEC61A1

Gene summary.

Gene information	Species	Human
	Gene symbol	SEC61A1
	Gene ID	29927
	Gene name	SEC61 translocon subunit alpha 1
	Gene Alias	ADTKD5
	Cytomap	3q21.3
	Gene Type	protein-coding
	GO ID	GO:0001655
	UniProtAcc	B3KME8

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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
29927	SEC61A1	HTA11_1938_2000001011	Human	Colorectum	AD	2.14e-03	3.53e-01	-0.0811
29927	SEC61A1	HTA11_347_2000001011	Human	Colorectum	AD	2.13e-11	4.11e-01	-0.1954
29927	SEC61A1	HTA11_2112_2000001011	Human	Colorectum	SER	1.54e-04	9.01e-01	-0.2196
29927	SEC61A1	HTA11_696_2000001011	Human	Colorectum	AD	1.09e-04	3.53e-01	-0.1464
29927	SEC61A1	HTA11_1391_2000001011	Human	Colorectum	AD	1.14e-03	5.02e-01	-0.059
29927	SEC61A1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	4.70e-02	1.01e+00	0.3487
29927	SEC61A1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.91e-17	7.10e-01	0.3859
29927	SEC61A1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.62e-03	3.32e-01	0.3005
29927	SEC61A1	A002-C-116	Human	Colorectum	FAP	1.69e-02	-1.26e-01	-0.0452
29927	SEC61A1	CRC-1-8810	Human	Colorectum	CRC	3.32e-02	1.76e-01	0.6257
29927	SEC61A1	LZE2T	Human	Esophagus	ESCC	1.15e-07	1.12e+00	0.082
29927	SEC61A1	LZE4T	Human	Esophagus	ESCC	2.81e-06	2.67e-01	0.0811
29927	SEC61A1	LZE7T	Human	Esophagus	ESCC	7.13e-15	1.22e+00	0.0667
29927	SEC61A1	LZE8T	Human	Esophagus	ESCC	2.23e-05	2.44e-01	0.067
29927	SEC61A1	LZE20T	Human	Esophagus	ESCC	4.11e-07	2.36e-01	0.0662
29927	SEC61A1	LZE22D1	Human	Esophagus	HGIN	7.63e-03	-6.72e-02	0.0595
29927	SEC61A1	LZE22T	Human	Esophagus	ESCC	5.60e-04	7.26e-01	0.068
29927	SEC61A1	LZE24T	Human	Esophagus	ESCC	2.99e-19	6.90e-01	0.0596
29927	SEC61A1	LZE21T	Human	Esophagus	ESCC	7.55e-05	-1.91e-02	0.0655
29927	SEC61A1	P1T-E	Human	Esophagus	ESCC	2.01e-12	9.37e-01	0.0875

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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
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:007097216	Prostate	Tumor	protein localization to endoplasmic reticulum	36/3246	74/18723	5.66e-10	2.95e-08	36
GO:007259913	Prostate	Tumor	establishment of protein localization to endoplasmic reticulum	23/3246	46/18723	3.87e-07	8.56e-06	23
GO:009015017	Prostate	Tumor	establishment of protein localization to membrane	77/3246	260/18723	6.46e-07	1.33e-05	77
GO:004504713	Prostate	Tumor	protein targeting to ER	21/3246	42/18723	1.24e-06	2.31e-05	21
GO:000165513	Prostate	Tumor	urogenital system development	90/3246	338/18723	1.08e-05	1.56e-04	90
GO:000661312	Prostate	Tumor	cotranslational protein targeting to membrane	15/3246	31/18723	6.78e-05	7.21e-04	15
GO:000182213	Prostate	Tumor	kidney development	74/3246	293/18723	3.68e-04	2.87e-03	74
GO:007200113	Prostate	Tumor	renal system development	75/3246	302/18723	5.74e-04	4.13e-03	75
GO:000702912	Prostate	Tumor	endoplasmic reticulum organization	27/3246	87/18723	1.24e-03	7.83e-03	27
GO:000662015	Prostate	Tumor	posttranslational protein targeting to endoplasmic reticulum membrane	7/3246	12/18723	1.64e-03	9.79e-03	7
GO:007180614	Prostate	Tumor	protein transmembrane transport	19/3246	59/18723	3.94e-03	2.00e-02	19
GO:003434113	Prostate	Tumor	response to interferon-gamma	37/3246	141/18723	5.07e-03	2.46e-02	37
GO:007200613	Prostate	Tumor	nephron development	37/3246	142/18723	5.73e-03	2.67e-02	37
GO:00066141	Prostate	Tumor	SRP-dependent cotranslational protein targeting to membrane	10/3246	26/18723	8.67e-03	3.76e-02	10
GO:006500212	Prostate	Tumor	intracellular protein transmembrane transport	16/3246	51/18723	1.02e-02	4.29e-02	16
GO:007259427	Skin	cSCC	establishment of protein localization to organelle	213/4864	422/18723	1.40e-27	5.15e-25	213
GO:000660527	Skin	cSCC	protein targeting	153/4864	314/18723	2.62e-18	3.36e-16	153
GO:009015024	Skin	cSCC	establishment of protein localization to membrane	123/4864	260/18723	8.34e-14	5.18e-12	123
GO:0070972110	Skin	cSCC	protein localization to endoplasmic reticulum	41/4864	74/18723	7.13e-08	1.78e-06	41
GO:007180610	Skin	cSCC	protein transmembrane transport	33/4864	59/18723	9.93e-07	1.78e-05	33

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa05110	Colorectum	AD	Vibrio cholerae infection	29/2092	50/8465	5.10e-07	7.12e-06	4.54e-06	29
hsa03060	Colorectum	AD	Protein export	14/2092	23/8465	2.43e-04	1.90e-03	1.21e-03	14
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa051101	Colorectum	AD	Vibrio cholerae infection	29/2092	50/8465	5.10e-07	7.12e-06	4.54e-06	29
hsa030601	Colorectum	AD	Protein export	14/2092	23/8465	2.43e-04	1.90e-03	1.21e-03	14
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa051102	Colorectum	SER	Vibrio cholerae infection	24/1580	50/8465	2.17e-06	3.13e-05	2.28e-05	24
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa051103	Colorectum	SER	Vibrio cholerae infection	24/1580	50/8465	2.17e-06	3.13e-05	2.28e-05	24
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
hsa051106	Colorectum	MSI-H	Vibrio cholerae infection	18/797	50/8465	2.77e-07	5.61e-06	4.70e-06	18
hsa030604	Colorectum	MSI-H	Protein export	11/797	23/8465	2.26e-06	3.65e-05	3.06e-05	11
hsa04145	Colorectum	MSI-H	Phagosome	27/797	152/8465	8.74e-04	1.01e-02	8.48e-03	27
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa051107	Colorectum	MSI-H	Vibrio cholerae infection	18/797	50/8465	2.77e-07	5.61e-06	4.70e-06	18
hsa030605	Colorectum	MSI-H	Protein export	11/797	23/8465	2.26e-06	3.65e-05	3.06e-05	11
hsa041451	Colorectum	MSI-H	Phagosome	27/797	152/8465	8.74e-04	1.01e-02	8.48e-03	27

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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

SEC61A1

SNV

Missense_Mutation

c.729N>A

p.Met243Ile

p.M243I

P61619

protein_coding

tolerated(0.2)

benign(0.003)

TCGA-A2-A0YL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

SEC61A1

SNV

Missense_Mutation

c.584N>G

p.Ala195Gly

p.A195G

P61619

protein_coding

deleterious(0.03)

benign(0.104)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SEC61A1

SNV

Missense_Mutation

c.691N>T

p.Arg231Trp

p.R231W

P61619

protein_coding

deleterious(0.03)

probably_damaging(0.926)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC61A1

SNV

Missense_Mutation

novel

c.1157C>T

p.Ser386Phe

p.S386F

P61619

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SEC61A1

SNV

Missense_Mutation

novel

c.791N>C

p.Asp264Ala

p.D264A

P61619

protein_coding

tolerated(0.11)

benign(0.026)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

SEC61A1

SNV

Missense_Mutation

c.1253N>T

p.Pro418Leu

p.P418L

P61619

protein_coding

deleterious(0.01)

possibly_damaging(0.869)

TCGA-D8-A140-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin+cyclophosphamid

SEC61A1

insertion

Frame_Shift_Ins

novel

c.1392_1393insTGGACATGTGTTGTTTCTTTCCATGCAGGGCATC

p.Gln465TrpfsTer73

p.Q465Wfs*73

P61619

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC61A1

insertion

Nonsense_Mutation

novel

c.946_947insGAATTTGCCTGCTAATCACCATTCAGGTAATTATTATGCTAACA

p.Leu316Ter

p.L316*

P61619

protein_coding

TCGA-BH-A0BD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SEC61A1

SNV

Missense_Mutation

c.706N>T

p.Arg236Cys

p.R236C

P61619

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SEC61A1

SNV

Missense_Mutation

novel

c.98N>C

p.Leu33Pro

p.L33P

P61619

protein_coding

deleterious(0)

possibly_damaging(0.861)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

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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