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: OPRM1

Gene summary for OPRM1

Gene summary.

Gene information	Species	Human
	Gene symbol	OPRM1
	Gene ID	4988
	Gene name	opioid receptor mu 1
	Gene Alias	LMOR
	Cytomap	6q25.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	G8XRH5

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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
4988	OPRM1	HCC1	Human	Liver	HCC	2.10e-06	5.49e-01	0.5336
4988	OPRM1	HCC2	Human	Liver	HCC	1.12e-12	7.51e-01	0.5341
4988	OPRM1	HCC5	Human	Liver	HCC	1.57e-04	3.51e-01	0.4932

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:003166722	Liver	HCC	response to nutrient levels	276/7958	474/18723	2.30e-12	1.08e-10	276
GO:019873821	Liver	HCC	cell-cell signaling by wnt	247/7958	446/18723	2.11e-08	4.96e-07	247
GO:004206022	Liver	HCC	wound healing	219/7958	422/18723	5.34e-05	5.04e-04	219
GO:009730522	Liver	HCC	response to alcohol	138/7958	253/18723	6.91e-05	6.26e-04	138
GO:004851121	Liver	HCC	rhythmic process	156/7958	298/18723	3.54e-04	2.46e-03	156
GO:001072011	Liver	HCC	positive regulation of cell development	155/7958	298/18723	5.39e-04	3.48e-03	155
GO:003249611	Liver	HCC	response to lipopolysaccharide	174/7958	343/18723	1.19e-03	6.62e-03	174
GO:000223711	Liver	HCC	response to molecule of bacterial origin	181/7958	363/18723	2.58e-03	1.24e-02	181
GO:19049501	Liver	HCC	negative regulation of establishment of protein localization	72/7958	131/18723	2.65e-03	1.27e-02	72
GO:00507674	Liver	HCC	regulation of neurogenesis	181/7958	364/18723	3.00e-03	1.40e-02	181
GO:00093146	Liver	HCC	response to radiation	223/7958	456/18723	3.08e-03	1.43e-02	223
GO:00507693	Liver	HCC	positive regulation of neurogenesis	116/7958	225/18723	3.67e-03	1.63e-02	116
GO:00025262	Liver	HCC	acute inflammatory response	62/7958	112/18723	4.06e-03	1.77e-02	62
GO:00512241	Liver	HCC	negative regulation of protein transport	69/7958	127/18723	4.67e-03	2.01e-02	69
GO:003559212	Liver	HCC	establishment of protein localization to extracellular region	176/7958	360/18723	7.96e-03	3.15e-02	176
GO:00432791	Liver	HCC	response to alkaloid	62/7958	115/18723	8.79e-03	3.42e-02	62
GO:000930612	Liver	HCC	protein secretion	175/7958	359/18723	9.32e-03	3.57e-02	175
GO:00454712	Liver	HCC	response to ethanol	72/7958	137/18723	1.10e-02	4.07e-02	72

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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

OPRM1

SNV

Missense_Mutation

c.1183N>C

p.Val395Leu

p.V395L

P35372

protein_coding

deleterious(0.05)

probably_damaging(0.938)

TCGA-AR-A1AH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

OPRM1

SNV

Missense_Mutation

c.1121N>T

p.Thr374Ile

p.T374I

P35372

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

OPRM1

SNV

Missense_Mutation

c.1094N>G

p.Glu365Gly

p.E365G

P35372

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-BH-A18Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

OPRM1

SNV

Missense_Mutation

c.1397N>C

p.Arg466Thr

p.R466T

P35372

protein_coding

tolerated(0.1)

probably_damaging(0.962)

TCGA-E2-A1IH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

aromasin

OPRM1

deletion

Frame_Shift_Del

c.250_256delCACAGCG

p.His84ValfsTer45

p.H84Vfs*45

P35372

protein_coding

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

OPRM1

insertion

Frame_Shift_Ins

novel

c.496_497insCAAATAAT

p.Ile166ThrfsTer25

p.I166Tfs*25

P35372

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OPRM1

SNV

Missense_Mutation

novel

c.590C>T

p.Ala197Val

p.A197V

P35372

protein_coding

tolerated(0.58)

probably_damaging(0.992)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

OPRM1

SNV

Missense_Mutation

c.1328N>T

p.Arg443Ile

p.R443I

P35372

protein_coding

deleterious(0)

probably_damaging(0.967)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

OPRM1

SNV

Missense_Mutation

rs199560373

c.517G>A

p.Val173Met

p.V173M

P35372

protein_coding

deleterious(0.01)

probably_damaging(0.982)

TCGA-ZJ-AAXF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

OPRM1

SNV

Missense_Mutation

novel

c.28N>A

p.Glu10Lys

p.E10K

P35372

protein_coding

benign(0.015)

TCGA-ZJ-AAXJ-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
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		LEVOMETHADYL ACETATE
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		AIKO-150
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	agonist	405067320
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	antagonist	CHEMBL426084	SAMIDORPHAN
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		tramadol	TRAMADOL	21837673,30549211
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		paclitaxel	PACLITAXEL	23963862
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		LOPERAMIDE	LOPERAMIDE
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	agonist	CHEMBL1237055	HYDROMORPHONE HYDROCHLORIDE
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	antagonist	CHEMBL3039511	BEVENOPRAN
4988	OPRM1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	antagonist	CHEMBL2103878	ODELEPRAN

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