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: CAMLG

Gene summary for CAMLG

Gene summary.

Gene information	Species	Human
	Gene symbol	CAMLG
	Gene ID	819
	Gene name	calcium modulating ligand
	Gene Alias	CAML
	Cytomap	5q31.1
	Gene Type	protein-coding
	GO ID	GO:0001776
	UniProtAcc	P49069

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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
819	CAMLG	HTA11_1938_2000001011	Human	Colorectum	AD	4.11e-03	3.08e-01	-0.0811
819	CAMLG	HTA11_347_2000001011	Human	Colorectum	AD	2.12e-05	2.73e-01	-0.1954
819	CAMLG	HTA11_866_3004761011	Human	Colorectum	AD	9.47e-07	3.17e-01	0.096
819	CAMLG	HTA11_7663_2000001011	Human	Colorectum	SER	4.88e-02	3.70e-01	0.0131
819	CAMLG	HTA11_7696_3000711011	Human	Colorectum	AD	2.86e-10	3.03e-01	0.0674
819	CAMLG	HTA11_99999970781_79442	Human	Colorectum	MSS	2.95e-10	4.06e-01	0.294
819	CAMLG	HTA11_99999965062_69753	Human	Colorectum	MSI-H	3.75e-03	5.49e-01	0.3487
819	CAMLG	HTA11_99999965104_69814	Human	Colorectum	MSS	8.63e-04	3.45e-01	0.281
819	CAMLG	HTA11_99999971662_82457	Human	Colorectum	MSS	1.24e-24	7.55e-01	0.3859
819	CAMLG	HTA11_99999974143_84620	Human	Colorectum	MSS	6.75e-07	2.88e-01	0.3005
819	CAMLG	AEH-subject1	Human	Endometrium	AEH	3.98e-10	-3.98e-01	-0.3059
819	CAMLG	AEH-subject2	Human	Endometrium	AEH	4.03e-14	-4.24e-01	-0.2525
819	CAMLG	AEH-subject3	Human	Endometrium	AEH	1.20e-25	-5.16e-01	-0.2576
819	CAMLG	AEH-subject4	Human	Endometrium	AEH	5.25e-09	-3.56e-01	-0.2657
819	CAMLG	AEH-subject5	Human	Endometrium	AEH	5.04e-12	-4.49e-01	-0.2953
819	CAMLG	EEC-subject1	Human	Endometrium	EEC	2.02e-13	-3.96e-01	-0.2682
819	CAMLG	EEC-subject2	Human	Endometrium	EEC	6.00e-22	-5.23e-01	-0.2607
819	CAMLG	EEC-subject3	Human	Endometrium	EEC	5.48e-37	-4.30e-01	-0.2525
819	CAMLG	EEC-subject4	Human	Endometrium	EEC	8.96e-07	-3.58e-01	-0.2571
819	CAMLG	EEC-subject5	Human	Endometrium	EEC	1.27e-09	-3.54e-01	-0.249

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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:00017822	Thyroid	PTC	B cell homeostasis	17/5968	31/18723	6.74e-03	2.90e-02	17
GO:001049832	Thyroid	ATC	proteasomal protein catabolic process	309/6293	490/18723	1.78e-41	1.13e-37	309
GO:0043161210	Thyroid	ATC	proteasome-mediated ubiquitin-dependent protein catabolic process	265/6293	412/18723	7.09e-38	1.49e-34	265
GO:004217635	Thyroid	ATC	regulation of protein catabolic process	239/6293	391/18723	2.63e-29	1.85e-26	239
GO:190336235	Thyroid	ATC	regulation of cellular protein catabolic process	168/6293	255/18723	3.50e-26	1.58e-23	168
GO:190305035	Thyroid	ATC	regulation of proteolysis involved in cellular protein catabolic process	146/6293	221/18723	4.18e-23	1.20e-20	146
GO:006113633	Thyroid	ATC	regulation of proteasomal protein catabolic process	128/6293	187/18723	1.63e-22	4.30e-20	128
GO:2000058210	Thyroid	ATC	regulation of ubiquitin-dependent protein catabolic process	116/6293	164/18723	2.15e-22	5.43e-20	116
GO:0032434210	Thyroid	ATC	regulation of proteasomal ubiquitin-dependent protein catabolic process	100/6293	134/18723	2.41e-22	5.86e-20	100
GO:190332034	Thyroid	ATC	regulation of protein modification by small protein conjugation or removal	152/6293	242/18723	9.76e-21	1.71e-18	152
GO:003164734	Thyroid	ATC	regulation of protein stability	177/6293	298/18723	4.08e-20	6.46e-18	177
GO:003139634	Thyroid	ATC	regulation of protein ubiquitination	132/6293	210/18723	3.13e-18	3.98e-16	132
GO:009015031	Thyroid	ATC	establishment of protein localization to membrane	150/6293	260/18723	1.05e-15	7.96e-14	150
GO:005082134	Thyroid	ATC	protein stabilization	117/6293	191/18723	3.98e-15	2.71e-13	117
GO:003139734	Thyroid	ATC	negative regulation of protein ubiquitination	56/6293	83/18723	2.90e-10	8.20e-09	56
GO:003133035	Thyroid	ATC	negative regulation of cellular catabolic process	136/6293	262/18723	6.47e-10	1.71e-08	136
GO:000989529	Thyroid	ATC	negative regulation of catabolic process	159/6293	320/18723	1.61e-09	3.99e-08	159
GO:190332135	Thyroid	ATC	negative regulation of protein modification by small protein conjugation or removal	60/6293	95/18723	3.53e-09	8.14e-08	60
GO:0048872210	Thyroid	ATC	homeostasis of number of cells	135/6293	272/18723	2.92e-08	5.50e-07	135
GO:200005934	Thyroid	ATC	negative regulation of ubiquitin-dependent protein catabolic process	34/6293	48/18723	1.49e-07	2.41e-06	34

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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

CAMLG

SNV

Missense_Mutation

rs143564828

c.310N>A

p.Glu104Lys

p.E104K

P49069

protein_coding

deleterious(0.01)

benign(0.266)

TCGA-HM-A3JK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CAMLG

SNV

Missense_Mutation

novel

c.133N>C

p.Asn45His

p.N45H

P49069

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

CAMLG

SNV

Missense_Mutation

c.71C>T

p.Ala24Val

p.A24V

P49069

protein_coding

tolerated_low_confidence(0.07)

possibly_damaging(0.558)

TCGA-AD-5900-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CAMLG

SNV

Missense_Mutation

rs751766092

c.566N>A

p.Arg189Gln

p.R189Q

P49069

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.946)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

CAMLG

SNV

Missense_Mutation

rs765331970

c.763N>A

p.Glu255Lys

p.E255K

P49069

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

CAMLG

SNV

Missense_Mutation

novel

c.308N>T

p.Ala103Val

p.A103V

P49069

protein_coding

tolerated(0.2)

benign(0)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

CAMLG

SNV

Missense_Mutation

novel

c.204N>T

p.Gln68His

p.Q68H

P49069

protein_coding

tolerated(0.57)

benign(0)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CAMLG

SNV

Missense_Mutation

rs757373789

c.446N>A

p.Arg149His

p.R149H

P49069

protein_coding

tolerated_low_confidence(0.19)

benign(0.006)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CAMLG

SNV

Missense_Mutation

rs765331970

c.763N>A

p.Glu255Lys

p.E255K

P49069

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CAMLG

SNV

Missense_Mutation

novel

c.868T>C

p.Tyr290His

p.Y290H

P49069

protein_coding

deleterious(0.02)

possibly_damaging(0.748)

TCGA-B5-A3FA-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
819	CAMLG	NA		CYCLOSPORINE A
819	CAMLG	NA		CYCLOSPORINE	CYCLOSPORINE

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