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: RIN1

Gene summary for RIN1

Gene summary.

Gene information	Species	Human
	Gene symbol	RIN1
	Gene ID	9610
	Gene name	Ras and Rab interactor 1
	Gene Alias	RIN1
	Cytomap	11q13.2
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	A0A0S2Z4U0

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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
9610	RIN1	P2T-E	Human	Esophagus	ESCC	5.72e-05	6.96e-02	0.1177
9610	RIN1	P4T-E	Human	Esophagus	ESCC	1.34e-05	2.19e-01	0.1323
9610	RIN1	P5T-E	Human	Esophagus	ESCC	9.64e-13	2.60e-01	0.1327
9610	RIN1	P8T-E	Human	Esophagus	ESCC	1.34e-04	7.71e-02	0.0889
9610	RIN1	P11T-E	Human	Esophagus	ESCC	3.46e-07	5.08e-01	0.1426
9610	RIN1	P15T-E	Human	Esophagus	ESCC	6.52e-06	2.51e-01	0.1149
9610	RIN1	P16T-E	Human	Esophagus	ESCC	2.01e-12	1.62e-01	0.1153
9610	RIN1	P17T-E	Human	Esophagus	ESCC	5.49e-10	5.31e-01	0.1278
9610	RIN1	P20T-E	Human	Esophagus	ESCC	4.34e-12	3.10e-01	0.1124
9610	RIN1	P21T-E	Human	Esophagus	ESCC	1.52e-25	5.19e-01	0.1617
9610	RIN1	P22T-E	Human	Esophagus	ESCC	1.59e-11	1.28e-01	0.1236
9610	RIN1	P23T-E	Human	Esophagus	ESCC	6.60e-08	2.23e-01	0.108
9610	RIN1	P24T-E	Human	Esophagus	ESCC	3.05e-12	2.07e-01	0.1287
9610	RIN1	P26T-E	Human	Esophagus	ESCC	1.80e-10	2.27e-01	0.1276
9610	RIN1	P27T-E	Human	Esophagus	ESCC	9.03e-14	1.74e-01	0.1055
9610	RIN1	P28T-E	Human	Esophagus	ESCC	1.09e-05	1.59e-01	0.1149
9610	RIN1	P31T-E	Human	Esophagus	ESCC	2.22e-08	1.56e-01	0.1251
9610	RIN1	P32T-E	Human	Esophagus	ESCC	2.88e-14	2.84e-01	0.1666
9610	RIN1	P36T-E	Human	Esophagus	ESCC	1.82e-08	2.11e-01	0.1187
9610	RIN1	P37T-E	Human	Esophagus	ESCC	1.84e-21	5.52e-01	0.1371

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:006049115	Prostate	Tumor	regulation of cell projection assembly	52/3246	188/18723	2.71e-04	2.24e-03	52
GO:003109915	Prostate	Tumor	regeneration	54/3246	198/18723	3.07e-04	2.47e-03	54
GO:012003215	Prostate	Tumor	regulation of plasma membrane bounded cell projection assembly	51/3246	186/18723	3.87e-04	2.99e-03	51
GO:009917312	Prostate	Tumor	postsynapse organization	47/3246	168/18723	3.94e-04	3.03e-03	47
GO:005196211	Prostate	Tumor	positive regulation of nervous system development	69/3246	272/18723	4.99e-04	3.67e-03	69
GO:006100112	Prostate	Tumor	regulation of dendritic spine morphogenesis	18/3246	47/18723	5.21e-04	3.82e-03	18
GO:012003412	Prostate	Tumor	positive regulation of plasma membrane bounded cell projection assembly	32/3246	105/18723	6.58e-04	4.66e-03	32
GO:006099711	Prostate	Tumor	dendritic spine morphogenesis	21/3246	61/18723	9.70e-04	6.30e-03	21
GO:009917511	Prostate	Tumor	regulation of postsynapse organization	28/3246	90/18723	9.74e-04	6.31e-03	28
GO:001059113	Prostate	Tumor	regulation of lamellipodium assembly	16/3246	42/18723	1.12e-03	7.16e-03	16
GO:005196011	Prostate	Tumor	regulation of nervous system development	102/3246	443/18723	1.20e-03	7.60e-03	102
GO:003300211	Prostate	Tumor	muscle cell proliferation	61/3246	248/18723	2.26e-03	1.28e-02	61
GO:00434033	Prostate	Tumor	skeletal muscle tissue regeneration	14/3246	37/18723	2.43e-03	1.36e-02	14
GO:00148121	Prostate	Tumor	muscle cell migration	31/3246	110/18723	3.15e-03	1.65e-02	31
GO:00609991	Prostate	Tumor	positive regulation of dendritic spine development	15/3246	42/18723	3.32e-03	1.73e-02	15
GO:003003213	Prostate	Tumor	lamellipodium assembly	22/3246	72/18723	4.15e-03	2.08e-02	22
GO:001097611	Prostate	Tumor	positive regulation of neuron projection development	42/3246	163/18723	4.24e-03	2.12e-02	42
GO:006053812	Prostate	Tumor	skeletal muscle organ development	42/3246	166/18723	5.98e-03	2.77e-02	42
GO:004544511	Prostate	Tumor	myoblast differentiation	24/3246	84/18723	7.23e-03	3.24e-02	24
GO:000751713	Prostate	Tumor	muscle organ development	74/3246	327/18723	8.03e-03	3.54e-02	74

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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

RIN1

SNV

Missense_Mutation

novel

c.1624N>G

p.Leu542Val

p.L542V

Q13671

protein_coding

tolerated(0.46)

benign(0.19)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

RIN1

SNV

Missense_Mutation

novel

c.2022N>A

p.Phe674Leu

p.F674L

Q13671

protein_coding

deleterious(0)

probably_damaging(0.93)

TCGA-A1-A0SE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RIN1

SNV

Missense_Mutation

c.73C>G

p.Leu25Val

p.L25V

Q13671

protein_coding

tolerated_low_confidence(0.1)

benign(0.069)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RIN1

SNV

Missense_Mutation

novel

c.1291G>A

p.Val431Ile

p.V431I

Q13671

protein_coding

tolerated(0.24)

benign(0.005)

TCGA-AO-A03V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

RIN1

SNV

Missense_Mutation

c.803N>G

p.Pro268Arg

p.P268R

Q13671

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-D8-A27T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicine+cyclophosphamide

RIN1

SNV

Missense_Mutation

rs62619978

c.2245N>T

p.Arg749Trp

p.R749W

Q13671

protein_coding

deleterious_low_confidence(0.03)

benign(0.183)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

RIN1

insertion

Nonsense_Mutation

novel

c.1822_1823insCATAGCTGCATCCAAAAGAGGCCCAGGTCATCTAACCTAAGGAGAAT

p.Arg608ProfsTer2

p.R608Pfs*2

Q13671

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RIN1

insertion

Frame_Shift_Ins

novel

c.1770_1771insACTTGTTTTTGCTTCTCCTCCTGCATAGCACCTCCTCCGAGTAG

p.Gly591ThrfsTer25

p.G591Tfs*25

Q13671

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

RIN1

insertion

Nonsense_Mutation

novel

c.1770_1771insAATAGGACCTACCTCCTGGGGTTGAGGTGAAGATTAAATG

p.Gly591AsnfsTer10

p.G591Nfs*10

Q13671

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RIN1

SNV

Missense_Mutation

novel

c.1922N>T

p.Ser641Phe

p.S641F

Q13671

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

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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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