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: POR

Gene summary for POR

Gene summary.

Gene information	Species	Human
	Gene symbol	POR
	Gene ID	5447
	Gene name	cytochrome p450 oxidoreductase
	Gene Alias	CPR
	Cytomap	7q11.23
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	P16435

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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
5447	POR	LZE2T	Human	Esophagus	ESCC	9.89e-14	1.20e+00	0.082
5447	POR	LZE4T	Human	Esophagus	ESCC	1.27e-07	2.39e-01	0.0811
5447	POR	LZE5T	Human	Esophagus	ESCC	5.35e-05	5.12e-01	0.0514
5447	POR	LZE7T	Human	Esophagus	ESCC	2.32e-09	5.69e-01	0.0667
5447	POR	LZE8T	Human	Esophagus	ESCC	5.63e-16	5.68e-01	0.067
5447	POR	LZE20T	Human	Esophagus	ESCC	2.05e-21	5.43e-01	0.0662
5447	POR	LZE21D1	Human	Esophagus	HGIN	5.60e-03	4.64e-01	0.0632
5447	POR	LZE22D1	Human	Esophagus	HGIN	1.89e-07	4.07e-01	0.0595
5447	POR	LZE22T	Human	Esophagus	ESCC	5.25e-12	1.11e+00	0.068
5447	POR	LZE24D1	Human	Esophagus	HGIN	1.57e-03	5.35e-01	0.054
5447	POR	LZE24T	Human	Esophagus	ESCC	1.21e-17	5.43e-01	0.0596
5447	POR	LZE21T	Human	Esophagus	ESCC	4.32e-13	7.25e-01	0.0655
5447	POR	LZE6T	Human	Esophagus	ESCC	1.95e-03	3.18e-01	0.0845
5447	POR	P1T-E	Human	Esophagus	ESCC	2.35e-19	1.04e+00	0.0875
5447	POR	P2T-E	Human	Esophagus	ESCC	1.24e-26	4.39e-01	0.1177
5447	POR	P4T-E	Human	Esophagus	ESCC	1.54e-33	7.57e-01	0.1323
5447	POR	P5T-E	Human	Esophagus	ESCC	1.60e-19	4.50e-01	0.1327
5447	POR	P8T-E	Human	Esophagus	ESCC	3.03e-41	8.58e-01	0.0889
5447	POR	P9T-E	Human	Esophagus	ESCC	2.75e-36	7.67e-01	0.1131
5447	POR	P10T-E	Human	Esophagus	ESCC	8.39e-68	1.26e+00	0.116

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0097305112	Skin	cSCC	response to alcohol	83/4864	253/18723	8.81e-03	4.05e-02	83
GO:00323502	Skin	cSCC	regulation of hormone metabolic process	16/4864	35/18723	9.09e-03	4.16e-02	16
GO:00713988	Skin	cSCC	cellular response to fatty acid	17/4864	38/18723	9.41e-03	4.25e-02	17
GO:000600610	Skin	cSCC	glucose metabolic process	66/4864	196/18723	9.75e-03	4.32e-02	66
GO:009013025	Skin	cSCC	tissue migration	115/4864	365/18723	9.81e-03	4.33e-02	115
GO:000166727	Skin	cSCC	ameboidal-type cell migration	146/4864	475/18723	1.05e-02	4.58e-02	146
GO:00060916	Stomach	GC	generation of precursor metabolites and energy	88/1159	490/18723	6.82e-20	9.27e-17	88
GO:00229006	Stomach	GC	electron transport chain	41/1159	175/18723	7.75e-14	4.68e-11	41
GO:00525476	Stomach	GC	regulation of peptidase activity	67/1159	461/18723	5.35e-11	1.10e-08	67
GO:00525486	Stomach	GC	regulation of endopeptidase activity	63/1159	432/18723	1.76e-10	2.82e-08	63
GO:00066315	Stomach	GC	fatty acid metabolic process	55/1159	390/18723	8.63e-09	8.38e-07	55
GO:00094106	Stomach	GC	response to xenobiotic stimulus	61/1159	462/18723	1.68e-08	1.43e-06	61
GO:00458616	Stomach	GC	negative regulation of proteolysis	50/1159	351/18723	2.96e-08	2.33e-06	50
GO:00513466	Stomach	GC	negative regulation of hydrolase activity	51/1159	379/18723	1.38e-07	8.14e-06	51
GO:20001166	Stomach	GC	regulation of cysteine-type endopeptidase activity	37/1159	235/18723	1.47e-07	8.52e-06	37
GO:00104666	Stomach	GC	negative regulation of peptidase activity	38/1159	262/18723	8.47e-07	4.18e-05	38
GO:00109516	Stomach	GC	negative regulation of endopeptidase activity	37/1159	252/18723	8.69e-07	4.26e-05	37
GO:00316676	Stomach	GC	response to nutrient levels	56/1159	474/18723	2.47e-06	1.06e-04	56
GO:00432816	Stomach	GC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	31/1159	209/18723	5.31e-06	2.11e-04	31
GO:00462096	Stomach	GC	nitric oxide metabolic process	16/1159	81/18723	3.09e-05	8.48e-04	16

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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
ADIPOQ	ADIPOR2	ADIPOQ_ADIPOR2	ADIPONECTIN	CRC	ADJ
ADIPOQ	ADIPOR2	ADIPOQ_ADIPOR2	ADIPONECTIN	CRC	FAP

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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

POR

SNV

Missense_Mutation

c.1987G>A

p.Asp663Asn

p.D663N

P16435

protein_coding

tolerated(0.23)

benign(0.009)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

POR

SNV

Missense_Mutation

rs781866008

c.838N>A

p.Asp280Asn

p.D280N

P16435

protein_coding

deleterious(0.03)

benign(0.41)

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

POR

SNV

Missense_Mutation

rs782053091

c.709N>A

p.Glu237Lys

p.E237K

P16435

protein_coding

deleterious(0.05)

benign(0.182)

TCGA-BH-A0AU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

POR

SNV

Missense_Mutation

novel

c.893N>A

p.Gly298Glu

p.G298E

P16435

protein_coding

deleterious(0.01)

benign(0.376)

TCGA-GM-A3NY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

POR

insertion

Frame_Shift_Ins

novel

c.937_938insG

p.Ser313CysfsTer6

p.S313Cfs*6

P16435

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

POR

insertion

Nonsense_Mutation

novel

c.938_939insTTGAACCTGGGAGG

p.Lys314Ter

p.K314*

P16435

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

POR

deletion

Frame_Shift_Del

novel

c.1514_1524delAGAACGGCGGC

p.Glu505AlafsTer66

p.E505Afs*66

P16435

protein_coding

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

POR

deletion

In_Frame_Del

c.443_445delNNN

p.Thr149del

p.T149del

P16435

protein_coding

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

POR

SNV

Missense_Mutation

rs367782552

c.773C>T

p.Ala258Val

p.A258V

P16435

protein_coding

tolerated(0.29)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

POR

SNV

Missense_Mutation

novel

c.1897N>T

p.Gly633Trp

p.G633W

P16435

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
5447	POR	ENZYME, DRUGGABLE GENOME		sirolimus	SIROLIMUS	23974086
5447	POR	ENZYME, DRUGGABLE GENOME		midazolam	MIDAZOLAM	23324807,19801957
5447	POR	ENZYME, DRUGGABLE GENOME		cyclosporine	CYCLOSPORINE	29135906,24658827,24061445
5447	POR	ENZYME, DRUGGABLE GENOME		zidovudine	ZIDOVUDINE	22960662
5447	POR	ENZYME, DRUGGABLE GENOME		atorvastatin	ATORVASTATIN	25521355
5447	POR	ENZYME, DRUGGABLE GENOME		nicotine	NICOTINE
5447	POR	ENZYME, DRUGGABLE GENOME		tacrolimus	TACROLIMUS	23097010,25322286,26829596,30323313,24113216,26227094,21770725,24921414,24739669,25271728,24061445,28094348,29878980,29399716
5447	POR	ENZYME, DRUGGABLE GENOME		sunitinib	SUNITINIB	28117434

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