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MINOR PRESENTATION

Computational analysis of differentially expressed genes as


potential biomarker and therapeutics target in pancreatic
cancer.

Submitted by Under the Supervision


Priyanshu Sharma Of
Roll No. – 18/IBT/024 Dr. Shakti Sahi
INTRODUCTION

Pancreatic cancer arises when cells


proliferate uncontrollably and form
tumors in the pancreas rather than
maturing into healthy pancreatic
tissue.

Pancreatic cancer is the seventh


major cause of cancer-related death
that affects worldwide due to its poor
prognosis.

Lack of appropriate biomarker and


poor prognosis is a current challenge.

Fig.1 Structure of pancreas


(www.cancer.gov)
PATHOLOGY

•The diagnosis of pancreatic


cancer is complicated, no
effective screening, early
diagnosis, or treatment.

•Current treatment include


1.Radiation/Chemotherapy,
Immunotherapy and Surgical
removal of the tumor.

•The earliest stage pancreas


cancers are stage 0 and then
range from stages I through IV.

Fig2. Magnified image of tumor present in pancreas.


Source- www.healthlibrary.askapollo.com
TOOLS

STRING
MUTFUNC
PDB/UNIPROT

DAVID
GEPIA2
PUBMED

DRUG BANK COSMIC

ENRICHR
OBJECTIVE/METHODOLOGY

1.To study the differential expressed genes from the literature.

2.Pathway analysis and prognostic Drug target identification of


differential expressed genes.

3.Protein-Protein networking, Mutation and survival curve


analysis.
RESULTS
AHNAK2
LogFC = 4.6
CRP CTHRC1
LogFC=6.08 LogFC=4.9
FNDC1
LogFC=4.01
LUM
LogFC=4.3
9
Objective1:Differe
ntially expressed
genes in pancreatic
AMY1C COL11A1
LogFC=7.02 cancer LogFC=5.9

NEFL SULF1
LogFC=5.4 ANPEP LogFC=4.74
LogFC=5.7
Objective 2: Pathway analysis from ENRICHR

Fig.3 – Differentially expressed genes involved in different pathways.


POTENTIAL DRUG TARGETS AND PATHWAYS
S.NO GENE SYMBOL DRUG TARGETS DRUG AVAILABLE PATHWAYS

1. AHNAK2 HIF1-alpha Echinomycin and 1.MAPK SIGNALLING


doxorubicin PATHWAY
2.NF-KB
3.WNT

2. CRP No target CRx-139

3. COL11A1 circ-0005105 No drug available 1.AKT


2.TGF- beta

4. SULF1 GPC1,GPCSDC1,HSPG GENISTEIN, 1.WNT


’s. TRASTUZUMAB 2.ERK
AND BLEOMYCIN
5. CTHRC1 VEGF BEVACIZUMAB 1.TGF-β
AND SORAFENIB 2.AKT

TABLE:1 POTENTIAL DRUG TARGETS AND PATHWAYS


S.NO GENE SYMBOL DRUG TARGETS DRUG AVAILABLE PATHWAYS

6. LUM CD44,C-MYC Copper 1.AKT


2.TGF- beta
3.SMAD

7. FNDC1 NO TARGET NO DRUG NO Pathways

8. ANPEP Aminopeptidase N Ezetimibe and NO INFO.


Icatibant

9. NEFL Serine/threonine- Fostamatinib EGFR/AKT


protein kinase N1

10. AMY1C Alpha-amylase 1 Semaglutide Pancreatic


secretion

TABLE:1 POTENTIAL DRUG TARGETS AND PATHWAYS


OBJECTIVE 3: Protein-Protein interaction through STRING

Fig.4 Protein-Protein interactions of Fig.5 Protein-Protein interactions of


AHNAK2 CRP
Fig.6 Protein-Protein interactions of Fig.7 Protein-Protein interactions of
COL11A1 CTHRC1
STRING NETWORKING

PROTEINS COMBINED SCORE

AHNAK2 ANXA2 0.999

MYOF 0.826

CRP CFH 0.998

FCGR1A 0.995

FCN2 0.981

COL11A1 COL2A1 0.959

CTHRC1 FZD6 0.960

DVL1 0.926
AHNAK2 SULF1

R49Q, K877T, T66M, D316N,


D898Y, G904C, R440W, R486W,
K1139M, V1321M, G763V
K182R, D2441Y,
V3769L.

MUTATIONS

NEFL
COL11A1
A149V, R212C,
D98V, E686K, G772V, E208K
R1062C, P1148R, G976A,
P1109R, A1719V
SURVIVAL CURVE

AHNAK2 COL11A1

Fig.8 Survival curve of AHNAK2. Fig.9 Survival curve of COL11A1


SULF1 NEFL

Fig.10 Survival curve of SULF1. Fig.11 Survival curve of NEFL.


CONCLUSION

1. We identified AHNAK2, SULF1, CRP, LUM, CTHRC1


AND COL11A1 as potential biomarkers.

2. We observed impactful mutations, differential expression,


potent drug targets as well as key regulatory pathways in
them.

3. We observed pathways such as TGFB, MAPK, AKT to be


involved in pancreatic cancer.

4. Our analysis also showed NEFL, AMY1C and FNDC1 as


novel markers which should be studied further for better
prognosis of diseases.
REFERENCES
• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram
I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN
estimates of incidence and mortality worldwide for 36 cancers in
185 countries. CA Cancer J Clin. 2021.
• Ariyama J. Detection and prognosis of small pancreatic ductal
adenocarcinoma. Nihon Geka Gakkai Zasshi. 1997; 98(7): 592- 6.
• Kommalapati A. Tella S.H. Goyal G. et al. Contemporary
management of localized resectable pancreatic cancer. Cancers
(Basel). 2018; 10: 24.
• Hur C. Tramontano A.C. Dowling E.C. et al. Early pancreatic
ductal adenocarcinoma survival is dependent on size: positive
implications for future targeted screening.
Pancreas. 2016; 45: 1062-1066
• https://www.cancer.gov/types/pancreatic/patient/pancreatic-
treatment-pdq.

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