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: SDCCAG8

Gene summary for SDCCAG8

Gene summary.

Gene information	Species	Human
	Gene symbol	SDCCAG8
	Gene ID	10806
	Gene name	SHH signaling and ciliogenesis regulator SDCCAG8
	Gene Alias	BBS16
	Cytomap	1q43-q44
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q86SQ7

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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
10806	SDCCAG8	CA_HPV_3	Human	Cervix	CC	1.21e-02	8.87e-02	0.0414
10806	SDCCAG8	CCI_3	Human	Cervix	CC	1.51e-02	6.55e-01	0.516
10806	SDCCAG8	T3	Human	Cervix	CC	4.48e-02	1.37e-01	0.1389
10806	SDCCAG8	LZE2T	Human	Esophagus	ESCC	6.83e-14	1.99e+00	0.082
10806	SDCCAG8	LZE4T	Human	Esophagus	ESCC	4.21e-24	6.09e-01	0.0811
10806	SDCCAG8	LZE5T	Human	Esophagus	ESCC	1.15e-02	2.94e-01	0.0514
10806	SDCCAG8	LZE7T	Human	Esophagus	ESCC	3.59e-25	1.35e+00	0.0667
10806	SDCCAG8	LZE8T	Human	Esophagus	ESCC	1.16e-15	5.46e-01	0.067
10806	SDCCAG8	LZE20T	Human	Esophagus	ESCC	4.39e-05	1.08e-01	0.0662
10806	SDCCAG8	LZE22D1	Human	Esophagus	HGIN	1.46e-11	5.41e-01	0.0595
10806	SDCCAG8	LZE22T	Human	Esophagus	ESCC	8.66e-16	1.38e+00	0.068
10806	SDCCAG8	LZE24T	Human	Esophagus	ESCC	6.98e-30	8.87e-01	0.0596
10806	SDCCAG8	LZE21T	Human	Esophagus	ESCC	1.94e-14	6.70e-01	0.0655
10806	SDCCAG8	LZE6T	Human	Esophagus	ESCC	2.56e-06	1.45e-01	0.0845
10806	SDCCAG8	P1T-E	Human	Esophagus	ESCC	2.29e-24	1.51e+00	0.0875
10806	SDCCAG8	P2T-E	Human	Esophagus	ESCC	1.39e-80	1.31e+00	0.1177
10806	SDCCAG8	P4T-E	Human	Esophagus	ESCC	1.01e-38	9.80e-01	0.1323
10806	SDCCAG8	P5T-E	Human	Esophagus	ESCC	3.27e-92	1.94e+00	0.1327
10806	SDCCAG8	P8T-E	Human	Esophagus	ESCC	1.06e-37	6.64e-01	0.0889
10806	SDCCAG8	P9T-E	Human	Esophagus	ESCC	1.77e-23	5.01e-01	0.1131

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
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:00071639	Cervix	CC	establishment or maintenance of cell polarity	63/2311	218/18723	4.25e-11	8.76e-09	63
GO:00300108	Cervix	CC	establishment of cell polarity	42/2311	143/18723	4.30e-08	2.62e-06	42
GO:19021153	Cervix	CC	regulation of organelle assembly	40/2311	186/18723	2.92e-04	3.15e-03	40
GO:01200328	Cervix	CC	regulation of plasma membrane bounded cell projection assembly	38/2311	186/18723	1.14e-03	9.35e-03	38
GO:00604917	Cervix	CC	regulation of cell projection assembly	38/2311	188/18723	1.40e-03	1.10e-02	38
GO:00351487	Cervix	CC	tube formation	31/2311	148/18723	2.07e-03	1.51e-02	31
GO:19021156	Esophagus	HGIN	regulation of organelle assembly	46/2587	186/18723	4.63e-05	1.12e-03	46
GO:006049117	Esophagus	HGIN	regulation of cell projection assembly	39/2587	188/18723	5.61e-03	4.57e-02	39
GO:000716320	Esophagus	ESCC	establishment or maintenance of cell polarity	143/8552	218/18723	2.05e-09	4.65e-08	143
GO:003001018	Esophagus	ESCC	establishment of cell polarity	96/8552	143/18723	1.69e-07	2.67e-06	96
GO:003514815	Esophagus	ESCC	tube formation	96/8552	148/18723	1.86e-06	2.16e-05	96
GO:190211514	Esophagus	ESCC	regulation of organelle assembly	116/8552	186/18723	3.15e-06	3.53e-05	116
GO:00070982	Esophagus	ESCC	centrosome cycle	85/8552	130/18723	4.41e-06	4.69e-05	85
GO:00310233	Esophagus	ESCC	microtubule organizing center organization	92/8552	143/18723	5.04e-06	5.31e-05	92
GO:006049118	Esophagus	ESCC	regulation of cell projection assembly	110/8552	188/18723	2.60e-04	1.58e-03	110
GO:012003218	Esophagus	ESCC	regulation of plasma membrane bounded cell projection assembly	108/8552	186/18723	4.37e-04	2.46e-03	108
GO:00071636	Liver	NAFLD	establishment or maintenance of cell polarity	46/1882	218/18723	8.80e-07	4.60e-05	46
GO:00300106	Liver	NAFLD	establishment of cell polarity	34/1882	143/18723	1.41e-06	6.56e-05	34
GO:000716312	Liver	Cirrhotic	establishment or maintenance of cell polarity	82/4634	218/18723	1.55e-05	2.11e-04	82
GO:1902115	Liver	Cirrhotic	regulation of organelle assembly	66/4634	186/18723	6.66e-04	5.04e-03	66

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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

SDCCAG8

SNV

Missense_Mutation

c.1480G>C

p.Glu494Gln

p.E494Q

Q86SQ7

protein_coding

tolerated(0.09)

possibly_damaging(0.521)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SDCCAG8

SNV

Missense_Mutation

c.1126G>C

p.Glu376Gln

p.E376Q

Q86SQ7

protein_coding

deleterious(0)

probably_damaging(0.948)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SDCCAG8

SNV

Missense_Mutation

c.1696N>A

p.Glu566Lys

p.E566K

Q86SQ7

protein_coding

deleterious(0.03)

probably_damaging(0.997)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SDCCAG8

SNV

Missense_Mutation

c.431C>G

p.Ser144Cys

p.S144C

Q86SQ7

protein_coding

tolerated(0.07)

benign(0.024)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SDCCAG8

SNV

Missense_Mutation

novel

c.35N>G

p.Glu12Gly

p.E12G

Q86SQ7

protein_coding

deleterious(0)

possibly_damaging(0.747)

TCGA-D8-A1X9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin+cyclophosphamide

SDCCAG8

insertion

In_Frame_Ins

novel

c.48_49insACCGCAACCAACAAGGAC

p.Gln16_Tyr17insThrAlaThrAsnLysAsp

p.Q16_Y17insTATNKD

Q86SQ7

protein_coding

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

SDCCAG8

deletion

In_Frame_Del

c.1225_1230delNNNNNN

p.Ile410_Leu411del

p.I410_L411del

Q86SQ7

protein_coding

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SDCCAG8

deletion

Frame_Shift_Del

novel

c.1647delT

p.Phe549LeufsTer19

p.F549Lfs*19

Q86SQ7

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

SDCCAG8

SNV

Missense_Mutation

novel

c.1279A>G

p.Lys427Glu

p.K427E

Q86SQ7

protein_coding

deleterious(0)

benign(0.085)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SDCCAG8

SNV

Missense_Mutation

rs756420930

c.1722G>A

p.Met574Ile

p.M574I

Q86SQ7

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-DG-A2KK-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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

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