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:0090312	Oral cavity	OSCC	positive regulation of protein deacetylation	20/7305	25/18723	3.47e-05	3.11e-04	20
GO:00421582	Oral cavity	OSCC	lipoprotein biosynthetic process	57/7305	96/18723	4.17e-05	3.61e-04	57
GO:000189216	Oral cavity	OSCC	embryonic placenta development	50/7305	82/18723	4.58e-05	3.90e-04	50
GO:0006270	Oral cavity	OSCC	DNA replication initiation	25/7305	34/18723	4.63e-05	3.90e-04	25
GO:190370618	Oral cavity	OSCC	regulation of hemopoiesis	180/7305	367/18723	5.16e-05	4.30e-04	180
GO:00062753	Oral cavity	OSCC	regulation of DNA replication	62/7305	107/18723	5.49e-05	4.54e-04	62
GO:00094164	Oral cavity	OSCC	response to light stimulus	159/7305	320/18723	5.98e-05	4.92e-04	159
GO:19020991	Oral cavity	OSCC	regulation of metaphase/anaphase transition of cell cycle	40/7305	63/18723	7.19e-05	5.67e-04	40
GO:00481446	Oral cavity	OSCC	fibroblast proliferation	49/7305	81/18723	7.27e-05	5.72e-04	49
GO:00450502	Oral cavity	OSCC	protein insertion into ER membrane by stop-transfer membrane-anchor sequence	10/7305	10/18723	8.14e-05	6.26e-04	10
GO:00066651	Oral cavity	OSCC	sphingolipid metabolic process	84/7305	155/18723	8.64e-05	6.61e-04	84
GO:1902749	Oral cavity	OSCC	regulation of cell cycle G2/M phase transition	59/7305	102/18723	8.81e-05	6.72e-04	59
GO:19019895	Oral cavity	OSCC	positive regulation of cell cycle phase transition	65/7305	115/18723	1.03e-04	7.69e-04	65
GO:00075698	Oral cavity	OSCC	cell aging	73/7305	132/18723	1.05e-04	7.75e-04	73
GO:00069706	Oral cavity	OSCC	response to osmotic stress	50/7305	84/18723	1.11e-04	8.15e-04	50
GO:00002889	Oral cavity	OSCC	nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	36/7305	56/18723	1.12e-04	8.24e-04	36
GO:00103326	Oral cavity	OSCC	response to gamma radiation	36/7305	56/18723	1.12e-04	8.24e-04	36
GO:00481457	Oral cavity	OSCC	regulation of fibroblast proliferation	48/7305	80/18723	1.14e-04	8.35e-04	48
GO:0010972	Oral cavity	OSCC	negative regulation of G2/M transition of mitotic cell cycle	38/7305	60/18723	1.17e-04	8.46e-04	38
GO:1902750	Oral cavity	OSCC	negative regulation of cell cycle G2/M phase transition	39/7305	62/18723	1.19e-04	8.54e-04	39

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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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