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: CIT

Gene summary for CIT

Gene summary.

Gene information	Species	Human
	Gene symbol	CIT
	Gene ID	11113
	Gene name	citron rho-interacting serine/threonine kinase
	Gene Alias	CITK
	Cytomap	12q24.23
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	O14578

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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
11113	CIT	TD9	Human	Lung	IAC	1.02e-02	5.71e-01	0.088
11113	CIT	RNA-P6T1-P6T1-1	Human	Lung	MIAC	6.67e-04	9.05e-01	-0.0238

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:000184113	Oral cavity	LP	neural tube formation	39/4623	102/18723	1.64e-03	1.25e-02	39
GO:0034101110	Oral cavity	LP	erythrocyte homeostasis	47/4623	129/18723	1.91e-03	1.43e-02	47
GO:0002262110	Oral cavity	LP	myeloid cell homeostasis	55/4623	157/18723	2.33e-03	1.68e-02	55
GO:001402013	Oral cavity	LP	primary neural tube formation	36/4623	94/18723	2.34e-03	1.68e-02	36
GO:0045785110	Oral cavity	LP	positive regulation of cell adhesion	134/4623	437/18723	2.44e-03	1.74e-02	134
GO:0048872110	Oral cavity	LP	homeostasis of number of cells	87/4623	272/18723	3.75e-03	2.47e-02	87
GO:0030218110	Oral cavity	LP	erythrocyte differentiation	43/4623	120/18723	4.13e-03	2.66e-02	43
GO:006013515	Oral cavity	LP	maternal process involved in female pregnancy	25/4623	62/18723	4.74e-03	3.00e-02	25
GO:000184313	Oral cavity	LP	neural tube closure	33/4623	88/18723	5.09e-03	3.16e-02	33
GO:006141811	Oral cavity	LP	regulation of transcription from RNA polymerase II promoter in response to hypoxia	8/4623	13/18723	5.19e-03	3.19e-02	8
GO:000756914	Oral cavity	LP	cell aging	46/4623	132/18723	5.64e-03	3.40e-02	46
GO:006060613	Oral cavity	LP	tube closure	33/4623	89/18723	6.20e-03	3.67e-02	33
GO:006145818	Oral cavity	LP	reproductive system development	128/4623	427/18723	6.91e-03	3.96e-02	128
GO:004860817	Oral cavity	LP	reproductive structure development	127/4623	424/18723	7.31e-03	4.08e-02	127
GO:000756515	Oral cavity	LP	female pregnancy	63/4623	193/18723	7.56e-03	4.17e-02	63
GO:004578715	Oral cavity	LP	positive regulation of cell cycle	96/4623	313/18723	9.08e-03	4.85e-02	96
GO:006145810	Prostate	BPH	reproductive system development	126/3107	427/18723	1.35e-11	9.95e-10	126
GO:003009918	Prostate	BPH	myeloid cell differentiation	115/3107	381/18723	2.22e-11	1.51e-09	115
GO:004860810	Prostate	BPH	reproductive structure development	124/3107	424/18723	3.76e-11	2.43e-09	124
GO:007048217	Prostate	BPH	response to oxygen levels	104/3107	347/18723	3.13e-10	1.67e-08	104

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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

CIT

SNV

Missense_Mutation

rs779515686

c.4130N>T

p.Pro1377Leu

p.P1377L

O14578

protein_coding

deleterious(0)

benign(0.248)

TCGA-A2-A0EW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CIT

SNV

Missense_Mutation

c.5132C>T

p.Ser1711Phe

p.S1711F

O14578

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-A2-A0SV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate therapy

zometa

CIT

SNV

Missense_Mutation

novel

c.2482N>A

p.Glu828Lys

p.E828K

O14578

protein_coding

deleterious(0.04)

possibly_damaging(0.628)

TCGA-A2-A25C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CIT

SNV

Missense_Mutation

c.3097G>T

p.Val1033Leu

p.V1033L

O14578

protein_coding

tolerated(0.08)

probably_damaging(0.978)

TCGA-A8-A076-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CIT

SNV

Missense_Mutation

rs747447396

c.2839C>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CIT

SNV

Missense_Mutation

rs747447396

c.2839N>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

c.242N>T

p.Ser81Phe

p.S81F

O14578

protein_coding

deleterious(0.02)

benign(0.17)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.637N>T

p.His213Tyr

p.H213Y

O14578

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CIT

SNV

Missense_Mutation

rs368981957

c.5590N>A

p.Asp1864Asn

p.D1864N

O14578

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.1771N>A

p.Glu591Lys

p.E591K

O14578

protein_coding

tolerated(0.31)

benign(0.019)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

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

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