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: C6

Gene summary for C6

Gene summary.

Gene information	Species	Human
	Gene symbol	C6
	Gene ID	729
	Gene name	complement C6
	Gene Alias	C6
	Cytomap	5p13.1
	Gene Type	protein-coding
	GO ID	GO:0001701
	UniProtAcc	P13671

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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
729	C6	NAFLD1	Human	Liver	NAFLD	2.68e-11	1.17e+00	-0.04
729	C6	S43	Human	Liver	Cirrhotic	1.89e-08	3.61e-02	-0.0187
729	C6	HCC1_Meng	Human	Liver	HCC	9.17e-29	-5.13e-01	0.0246
729	C6	HCC2_Meng	Human	Liver	HCC	1.09e-10	-5.29e-01	0.0107
729	C6	cirrhotic1	Human	Liver	Cirrhotic	7.08e-14	-3.02e-01	0.0202
729	C6	cirrhotic2	Human	Liver	Cirrhotic	1.54e-20	-1.89e-01	0.0201
729	C6	cirrhotic3	Human	Liver	Cirrhotic	1.26e-10	-2.75e-01	0.0215
729	C6	HCC5	Human	Liver	HCC	1.54e-04	7.50e-01	0.4932
729	C6	Pt13.a	Human	Liver	HCC	1.32e-09	-4.40e-01	0.021
729	C6	Pt13.b	Human	Liver	HCC	4.54e-10	-3.65e-01	0.0251
729	C6	Pt14.d	Human	Liver	HCC	9.20e-09	-4.71e-01	0.0143
729	C6	S014	Human	Liver	HCC	2.49e-03	-5.07e-01	0.2254
729	C6	S015	Human	Liver	HCC	3.42e-03	-5.37e-01	0.2375
729	C6	S016	Human	Liver	HCC	4.74e-11	-5.59e-01	0.2243

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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:006145831	Oral cavity	NEOLP	reproductive system development	91/2005	427/18723	8.18e-11	9.00e-09	91
GO:000641734	Oral cavity	NEOLP	regulation of translation	97/2005	468/18723	9.94e-11	1.05e-08	97
GO:004860831	Oral cavity	NEOLP	reproductive structure development	90/2005	424/18723	1.30e-10	1.33e-08	90
GO:200123632	Oral cavity	NEOLP	regulation of extrinsic apoptotic signaling pathway	44/2005	151/18723	3.30e-10	2.97e-08	44
GO:006219733	Oral cavity	NEOLP	cellular response to chemical stress	75/2005	337/18723	4.87e-10	3.97e-08	75
GO:000189031	Oral cavity	NEOLP	placenta development	42/2005	144/18723	8.01e-10	6.02e-08	42
GO:009719133	Oral cavity	NEOLP	extrinsic apoptotic signaling pathway	55/2005	219/18723	1.07e-09	7.82e-08	55
GO:004586133	Oral cavity	NEOLP	negative regulation of proteolysis	76/2005	351/18723	1.40e-09	9.80e-08	76
GO:005254833	Oral cavity	NEOLP	regulation of endopeptidase activity	88/2005	432/18723	1.82e-09	1.18e-07	88
GO:006101332	Oral cavity	NEOLP	regulation of mRNA catabolic process	45/2005	166/18723	2.67e-09	1.64e-07	45
GO:000640131	Oral cavity	NEOLP	RNA catabolic process	63/2005	278/18723	5.63e-09	3.07e-07	63
GO:000170132	Oral cavity	NEOLP	in utero embryonic development	76/2005	367/18723	1.11e-08	5.44e-07	76
GO:190331331	Oral cavity	NEOLP	positive regulation of mRNA metabolic process	35/2005	118/18723	1.25e-08	5.94e-07	35
GO:007259432	Oral cavity	NEOLP	establishment of protein localization to organelle	84/2005	422/18723	1.30e-08	6.10e-07	84
GO:000189231	Oral cavity	NEOLP	embryonic placenta development	27/2005	82/18723	5.12e-08	2.08e-06	27
GO:005134631	Oral cavity	NEOLP	negative regulation of hydrolase activity	75/2005	379/18723	9.98e-08	3.66e-06	75
GO:000756831	Oral cavity	NEOLP	aging	69/2005	339/18723	1.05e-07	3.83e-06	69
GO:003300221	Oral cavity	NEOLP	muscle cell proliferation	55/2005	248/18723	1.11e-07	4.03e-06	55
GO:001046632	Oral cavity	NEOLP	negative regulation of peptidase activity	57/2005	262/18723	1.32e-07	4.65e-06	57
GO:004348832	Oral cavity	NEOLP	regulation of mRNA stability	40/2005	158/18723	1.54e-07	5.28e-06	40

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517114	Liver	NAFLD	Coronavirus disease - COVID-19	111/1043	232/8465	1.01e-41	3.32e-39	2.67e-39	111
hsa04610	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa0481010	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0517115	Liver	NAFLD	Coronavirus disease - COVID-19	111/1043	232/8465	1.01e-41	3.32e-39	2.67e-39	111
hsa046101	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa0481011	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0517122	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa0502014	Liver	Cirrhotic	Prion disease	152/2530	273/8465	1.84e-19	8.78e-18	5.41e-18	152
hsa046102	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa0481021	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0517132	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa0502015	Liver	Cirrhotic	Prion disease	152/2530	273/8465	1.84e-19	8.78e-18	5.41e-18	152
hsa046103	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa0481031	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0502022	Liver	HCC	Prion disease	195/4020	273/8465	3.26e-16	1.56e-14	8.67e-15	195
hsa0517142	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa046104	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa0481041	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0502032	Liver	HCC	Prion disease	195/4020	273/8465	3.26e-16	1.56e-14	8.67e-15	195
hsa0517152	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167

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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

SNV

Missense_Mutation

c.201N>C

p.Lys67Asn

p.K67N

P13671

protein_coding

tolerated(0.09)

possibly_damaging(0.717)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

SNV

Missense_Mutation

c.1672G>A

p.Asp558Asn

p.D558N

P13671

protein_coding

tolerated(0.09)

benign(0.29)

TCGA-A8-A09B-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

SNV

Missense_Mutation

c.1375N>G

p.Lys459Glu

p.K459E

P13671

protein_coding

deleterious(0)

probably_damaging(0.934)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

rs369381506

c.1067N>A

p.Arg356Gln

p.R356Q

P13671

protein_coding

tolerated(0.17)

benign(0.098)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

rs763860114

c.2522G>A

p.Arg841His

p.R841H

P13671

protein_coding

tolerated(0.19)

benign(0.35)

TCGA-C8-A12Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

c.311N>T

p.Arg104Ile

p.R104I

P13671

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

SNV

Missense_Mutation

novel

c.1177N>A

p.Glu393Lys

p.E393K

P13671

protein_coding

tolerated(0.24)

benign(0.169)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

insertion

Frame_Shift_Ins

rs762335076

c.828_829insG

p.Ser277GlufsTer15

p.S277Efs*15

P13671

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

deletion

Frame_Shift_Del

rs372345940

c.828delN

p.Ser277AlafsTer43

p.S277Afs*43

P13671

protein_coding

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

insertion

Frame_Shift_Ins

rs762335076

c.828dupG

p.Ser277GlufsTer15

p.S277Efs*15

P13671

protein_coding

TCGA-E9-A1NC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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