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: CANX

Gene summary for CANX

Gene summary.

Gene information	Species	Human
	Gene symbol	CANX
	Gene ID	821
	Gene name	calnexin
	Gene Alias	CNX
	Cytomap	5q35.3
	Gene Type	protein-coding
	GO ID	GO:0006457
	UniProtAcc	P27824

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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
821	CANX	GSM4909280	Human	Breast	Precancer	9.60e-03	-5.07e-01	0.0305
821	CANX	GSM4909282	Human	Breast	IDC	7.98e-06	-3.57e-01	-0.0288
821	CANX	GSM4909285	Human	Breast	IDC	1.11e-02	-1.36e-01	0.21
821	CANX	GSM4909286	Human	Breast	IDC	2.09e-12	-4.38e-01	0.1081
821	CANX	GSM4909287	Human	Breast	IDC	4.74e-03	4.71e-03	0.2057
821	CANX	GSM4909291	Human	Breast	IDC	4.59e-05	2.95e-01	0.1753
821	CANX	GSM4909294	Human	Breast	IDC	6.64e-07	-3.55e-01	0.2022
821	CANX	GSM4909296	Human	Breast	IDC	6.44e-13	-2.92e-01	0.1524
821	CANX	GSM4909297	Human	Breast	IDC	1.13e-16	-3.57e-01	0.1517
821	CANX	GSM4909298	Human	Breast	IDC	1.48e-02	5.65e-02	0.1551
821	CANX	GSM4909309	Human	Breast	IDC	2.83e-03	-6.20e-02	0.0483
821	CANX	GSM4909311	Human	Breast	IDC	7.73e-36	-5.13e-01	0.1534
821	CANX	GSM4909312	Human	Breast	IDC	9.83e-11	-1.06e-01	0.1552
821	CANX	GSM4909313	Human	Breast	IDC	3.23e-05	-5.39e-03	0.0391
821	CANX	GSM4909315	Human	Breast	IDC	1.41e-04	-4.02e-01	0.21
821	CANX	GSM4909316	Human	Breast	IDC	5.86e-09	-5.88e-01	0.21
821	CANX	GSM4909319	Human	Breast	IDC	6.87e-47	-6.36e-01	0.1563
821	CANX	GSM4909320	Human	Breast	IDC	1.68e-15	-5.18e-01	0.1575
821	CANX	GSM4909321	Human	Breast	IDC	4.83e-16	-3.34e-01	0.1559
821	CANX	brca1	Human	Breast	Precancer	2.92e-02	-2.80e-01	-0.0338

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00075688	Breast	Precancer	aging	41/1080	339/18723	5.95e-06	1.71e-04	41
GO:00349758	Breast	Precancer	protein folding in endoplasmic reticulum	6/1080	11/18723	1.31e-05	3.30e-04	6
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:00068986	Breast	Precancer	receptor-mediated endocytosis	27/1080	244/18723	9.01e-04	1.03e-02	27
GO:00716926	Breast	Precancer	protein localization to extracellular region	34/1080	368/18723	4.65e-03	3.58e-02	34
GO:00093067	Breast	Precancer	protein secretion	33/1080	359/18723	5.65e-03	4.08e-02	33
GO:00355927	Breast	Precancer	establishment of protein localization to extracellular region	33/1080	360/18723	5.89e-03	4.21e-02	33
GO:001603214	Breast	IDC	viral process	75/1434	415/18723	1.98e-12	4.02e-10	75
GO:000645713	Breast	IDC	protein folding	47/1434	212/18723	2.31e-11	3.86e-09	47
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75
GO:003497614	Breast	IDC	response to endoplasmic reticulum stress	43/1434	256/18723	8.42e-07	3.82e-05	43
GO:000756813	Breast	IDC	aging	52/1434	339/18723	1.14e-06	5.10e-05	52
GO:004316114	Breast	IDC	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1434	412/18723	9.55e-06	2.68e-04	57
GO:003497513	Breast	IDC	protein folding in endoplasmic reticulum	6/1434	11/18723	6.59e-05	1.35e-03	6
GO:000689813	Breast	IDC	receptor-mediated endocytosis	35/1434	244/18723	2.38e-04	3.75e-03	35
GO:007169212	Breast	IDC	protein localization to extracellular region	42/1434	368/18723	6.13e-03	4.38e-02	42

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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
hsa0461218	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0461219	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0461223	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0414522	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0461233	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0414532	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0516634	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0461242	Breast	DCIS	Antigen processing and presentation	25/846	78/8465	6.75e-08	1.28e-06	9.45e-07	25
hsa0414541	Breast	DCIS	Phagosome	35/846	152/8465	1.67e-06	2.45e-05	1.81e-05	35
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0516642	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0461252	Breast	DCIS	Antigen processing and presentation	25/846	78/8465	6.75e-08	1.28e-06	9.45e-07	25
hsa0414551	Breast	DCIS	Phagosome	35/846	152/8465	1.67e-06	2.45e-05	1.81e-05	35

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
CANX	MVA	Stomach	CAG	INHBB,HSP90B1,ST3GAL4, etc.	9.29e-02
CANX	LYMEND	Stomach	CSG	INHBB,HSP90B1,ST3GAL4, etc.	0.00e+00
CANX	MYOFIB	Stomach	WIM	INHBB,HSP90B1,ST3GAL4, etc.	1.23e-01
CANX	MSC	Stomach	WIM	INHBB,HSP90B1,ST3GAL4, etc.	8.59e-02

∗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

CANX

SNV

Missense_Mutation

novel

c.1057N>A

p.Pro353Thr

p.P353T

P27824

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CANX

SNV

Missense_Mutation

c.1196N>T

p.Pro399Leu

p.P399L

P27824

protein_coding

deleterious(0.01)

probably_damaging(0.949)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CANX

SNV

Missense_Mutation

c.274N>C

p.Asp92His

p.D92H

P27824

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-BH-A18V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CANX

insertion

In_Frame_Ins

novel

c.1602_1603insCTTGGG

p.Glu534_Lys535insLeuGly

p.E534_K535insLG

P27824

protein_coding

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CANX

insertion

In_Frame_Ins

novel

c.1603_1604insTCC

p.Lys535delinsIleGln

p.K535delinsIQ

P27824

protein_coding

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CANX

deletion

Frame_Shift_Del

rs760711956

c.1305delT

p.Phe435LeufsTer12

p.F435Lfs*12

P27824

protein_coding

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

CANX

deletion

Frame_Shift_Del

novel

c.135delN

p.Lys46AsnfsTer61

p.K46Nfs*61

P27824

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

CANX

SNV

Missense_Mutation

novel

c.1060N>G

p.Gln354Glu

p.Q354E

P27824

protein_coding

tolerated(0.28)

benign(0.078)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

CANX

SNV

Missense_Mutation

rs756081134

c.913N>A

p.Asp305Asn

p.D305N

P27824

protein_coding

tolerated(0.07)

probably_damaging(0.914)

TCGA-C5-A7CK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CANX

SNV

Missense_Mutation

novel

c.1244N>A

p.Arg415Lys

p.R415K

P27824

protein_coding

tolerated(1)

benign(0)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

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
821	CANX	NA		MPO	MYELOPEROXIDASE	11818449

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