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:190370821	Oral cavity	NEOLP	positive regulation of hemopoiesis	29/2005	157/18723	2.40e-03	1.53e-02	29
GO:003239231	Oral cavity	NEOLP	DNA geometric change	19/2005	90/18723	2.81e-03	1.73e-02	19
GO:003250821	Oral cavity	NEOLP	DNA duplex unwinding	18/2005	84/18723	3.02e-03	1.84e-02	18
GO:00456211	Oral cavity	NEOLP	positive regulation of lymphocyte differentiation	21/2005	104/18723	3.07e-03	1.87e-02	21
GO:004561921	Oral cavity	NEOLP	regulation of lymphocyte differentiation	31/2005	174/18723	3.10e-03	1.89e-02	31
GO:006021122	Oral cavity	NEOLP	regulation of nuclear-transcribed mRNA poly(A) tail shortening	6/2005	15/18723	3.18e-03	1.91e-02	6
GO:190015322	Oral cavity	NEOLP	positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	6/2005	15/18723	3.18e-03	1.91e-02	6
GO:007097231	Oral cavity	NEOLP	protein localization to endoplasmic reticulum	16/2005	74/18723	4.56e-03	2.55e-02	16
GO:000028822	Oral cavity	NEOLP	nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	13/2005	56/18723	5.38e-03	2.88e-02	13
GO:000283311	Oral cavity	NEOLP	positive regulation of response to biotic stimulus	29/2005	168/18723	6.52e-03	3.34e-02	29
GO:000660532	Oral cavity	NEOLP	protein targeting	48/2005	314/18723	7.23e-03	3.66e-02	48
GO:005125113	Oral cavity	NEOLP	positive regulation of lymphocyte activation	54/2005	362/18723	7.55e-03	3.77e-02	54
GO:000221831	Oral cavity	NEOLP	activation of innate immune response	12/2005	52/18723	7.72e-03	3.84e-02	12
GO:190015123	Oral cavity	NEOLP	regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	6/2005	18/18723	8.92e-03	4.25e-02	6
GO:007147014	Oral cavity	NEOLP	cellular response to osmotic stress	10/2005	41/18723	9.71e-03	4.55e-02	10
GO:000225313	Oral cavity	NEOLP	activation of immune response	55/2005	375/18723	9.87e-03	4.62e-02	55
GO:200123318	Prostate	BPH	regulation of apoptotic signaling pathway	134/3107	356/18723	5.06e-22	7.84e-19	134
GO:000641718	Prostate	BPH	regulation of translation	157/3107	468/18723	9.09e-20	5.63e-17	157
GO:190331116	Prostate	BPH	regulation of mRNA metabolic process	111/3107	288/18723	2.28e-19	1.17e-16	111
GO:007259416	Prostate	BPH	establishment of protein localization to organelle	142/3107	422/18723	4.01e-18	1.31e-15	142

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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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