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: CEACAM6

Gene summary for CEACAM6

Gene summary.

Gene information	Species	Human
	Gene symbol	CEACAM6
	Gene ID	4680
	Gene name	CEA cell adhesion molecule 6
	Gene Alias	CD66c
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0001952
	UniProtAcc	P40199

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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
4680	CEACAM6	C57	Human	Oral cavity	OSCC	8.90e-18	6.23e-01	0.1679
4680	CEACAM6	SYSMH6	Human	Oral cavity	OSCC	3.06e-22	1.24e+00	0.1275
4680	CEACAM6	HTA12-9-1	Human	Pancreas	PDAC	1.45e-23	1.11e+00	0.1532
4680	CEACAM6	HTA12-9-2	Human	Pancreas	PDAC	2.11e-03	3.51e-01	0.0835
4680	CEACAM6	HTA12-9-3	Human	Pancreas	PDAC	5.91e-13	1.24e+00	0.2045
4680	CEACAM6	DS20191261Tumor	Human	Pancreas	PDAC	1.42e-03	4.61e-01	0.1367
4680	CEACAM6	Pat01-B	Human	Stomach	GC	8.44e-27	6.92e-01	0.5754
4680	CEACAM6	Pat02-B	Human	Stomach	GC	1.17e-15	4.76e-01	0.0368
4680	CEACAM6	Pat03-B	Human	Stomach	GC	5.71e-32	8.37e-01	0.3693
4680	CEACAM6	Pat04-B	Human	Stomach	GC	1.27e-05	2.96e-01	-0.1483
4680	CEACAM6	Pat07-B	Human	Stomach	GC	1.37e-09	6.43e-01	0.0935
4680	CEACAM6	Pat10-B	Human	Stomach	GC	5.90e-21	1.13e+00	0.084
4680	CEACAM6	Pat12-B	Human	Stomach	GC	2.90e-50	1.10e+00	0.0325
4680	CEACAM6	Pat13-B	Human	Stomach	GC	4.19e-02	2.74e-01	0.0555
4680	CEACAM6	Pat16-B	Human	Stomach	GC	1.14e-05	2.85e-01	0.1918
4680	CEACAM6	Pat17-B	Human	Stomach	GC	2.46e-14	5.21e-01	0.3109
4680	CEACAM6	Pat18-B	Human	Stomach	GC	3.05e-03	2.60e-01	-0.0432
4680	CEACAM6	Pat19-B	Human	Stomach	GC	8.50e-19	7.24e-01	0.0826
4680	CEACAM6	Pat22-B	Human	Stomach	GC	7.52e-06	2.58e-01	-0.1042
4680	CEACAM6	Pat24-B	Human	Stomach	GC	1.57e-06	3.98e-01	-0.1184

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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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:0010811	Colorectum	AD	positive regulation of cell-substrate adhesion	53/3918	123/18723	2.30e-08	1.27e-06	53
GO:0010810	Colorectum	AD	regulation of cell-substrate adhesion	81/3918	221/18723	4.80e-08	2.55e-06	81
GO:0031589	Colorectum	AD	cell-substrate adhesion	116/3918	363/18723	4.68e-07	1.76e-05	116
GO:0001952	Colorectum	AD	regulation of cell-matrix adhesion	50/3918	128/18723	2.05e-06	6.05e-05	50
GO:0001954	Colorectum	AD	positive regulation of cell-matrix adhesion	27/3918	58/18723	1.12e-05	2.55e-04	27
GO:0007160	Colorectum	AD	cell-matrix adhesion	75/3918	233/18723	3.56e-05	6.45e-04	75
GO:0045785	Colorectum	AD	positive regulation of cell adhesion	122/3918	437/18723	2.65e-04	3.28e-03	122
GO:00108102	Colorectum	MSS	regulation of cell-substrate adhesion	73/3467	221/18723	1.56e-07	7.16e-06	73
GO:00108112	Colorectum	MSS	positive regulation of cell-substrate adhesion	47/3467	123/18723	2.28e-07	9.79e-06	47
GO:00315892	Colorectum	MSS	cell-substrate adhesion	104/3467	363/18723	1.35e-06	4.51e-05	104
GO:00019522	Colorectum	MSS	regulation of cell-matrix adhesion	45/3467	128/18723	5.75e-06	1.53e-04	45
GO:00019542	Colorectum	MSS	positive regulation of cell-matrix adhesion	23/3467	58/18723	1.39e-04	2.06e-03	23
GO:00071602	Colorectum	MSS	cell-matrix adhesion	65/3467	233/18723	2.77e-04	3.67e-03	65
GO:00457852	Colorectum	MSS	positive regulation of cell adhesion	110/3467	437/18723	2.94e-04	3.87e-03	110
GO:00108104	Colorectum	FAP	regulation of cell-substrate adhesion	68/2622	221/18723	9.67e-11	2.96e-08	68
GO:00315893	Colorectum	FAP	cell-substrate adhesion	93/2622	363/18723	2.48e-09	4.61e-07	93
GO:00108114	Colorectum	FAP	positive regulation of cell-substrate adhesion	43/2622	123/18723	3.82e-09	6.33e-07	43
GO:00019523	Colorectum	FAP	regulation of cell-matrix adhesion	42/2622	128/18723	4.73e-08	3.86e-06	42
GO:00071603	Colorectum	FAP	cell-matrix adhesion	63/2622	233/18723	1.13e-07	7.43e-06	63
GO:00019543	Colorectum	FAP	positive regulation of cell-matrix adhesion	22/2622	58/18723	5.19e-06	1.68e-04	22

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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

CEACAM6

SNV

Missense_Mutation

rs782366279

c.557N>T

p.Pro186Leu

p.P186L

P40199

protein_coding

tolerated(0.1)

benign(0.077)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

CEACAM6

insertion

Frame_Shift_Ins

novel

c.651_652insT

p.Gln218SerfsTer10

p.Q218Sfs*10

P40199

protein_coding

TCGA-A8-A07F-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CEACAM6

insertion

Nonsense_Mutation

novel

c.652_653insGTGCATCTGTTGTGTGACACACACACCTGCCAGGGGCTTTTA

p.Gln218delinsArgAlaSerValValTerHisThrHisLeuProGlyAlaPheLys

p.Q218delinsRASVV*HTHLPGAFK

P40199

protein_coding

TCGA-A8-A07F-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CEACAM6

insertion

Nonsense_Mutation

novel

c.706_707insCACACAGAAAATACAGCTAGGGGGGCAAAGTAGGACTAAAGCTT

p.Gly236AlafsTer7

p.G236Afs*7

P40199

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CEACAM6

SNV

Missense_Mutation

rs143238640

c.994N>A

p.Gly332Ser

p.G332S

P40199

protein_coding

tolerated(0.75)

benign(0.08)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CEACAM6

SNV

Missense_Mutation

c.29G>A

p.Arg10Lys

p.R10K

P40199

protein_coding

tolerated(0.36)

benign(0.331)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CEACAM6

SNV

Missense_Mutation

novel

c.215N>C

p.Arg72Thr

p.R72T

P40199

protein_coding

tolerated(0.68)

benign(0.012)

TCGA-VS-A8EL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CEACAM6

SNV

Missense_Mutation

c.808N>A

p.Ser270Thr

p.S270T

P40199

protein_coding

tolerated(0.11)

probably_damaging(0.936)

TCGA-F4-6570-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CEACAM6

insertion

Frame_Shift_Ins

novel

c.650_651insG

p.Ile217MetfsTer11

p.I217Mfs*11

P40199

protein_coding

TCGA-AA-3856-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

CEACAM6

insertion

Frame_Shift_Ins

novel

c.650_651insG

p.Ile217MetfsTer11

p.I217Mfs*11

P40199

protein_coding

TCGA-AA-3952-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

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
4680	CEACAM6	CELL SURFACE, DRUGGABLE GENOME		ANTISERUM		6388310

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