Biomarkers for early detection of pancreatic cancer – miRNAs as a potential diagnostic and therapeutic tool?

Figures & data

Table 1. Non-coding RNAs and PDAC tumorigenesis

PDAC promoting	Aliases for gene (genecards.org/)	Gene location (genenames.org/)	Increased expression promoting other cancers (malacards.org/)
MicroRNA
miR-21	MicroRNA 21	17q23.1	Multiple cancers
miR-155	MicroRNA 155	21q21.3	Multiple cancers
miR-221/222	MicroRNA 221/222	Xp11.3/ Xp11.3	Multiple cancers
miR-196b	MicroRNA 196b	7p15.2	Multiple cancers
miR-10a	MicroRNA 10a	17q21.32	Multiple cancers
Circular RNA
ciRS-7	CDR1 Antisense RNA	Xq27.1	Bladder cancer
circ-LDLRAD3	Low Density Lipoprotein Receptor Class A Domain Containing 3	11p13	No data
RHOT1	Ras Homolog Family Member T1	17q11.2	No data
ZMYM2	Zinc Finger MYM-Type Containing 2	13q12.11	Lymphoma, leukemia, myelofibrosis
IARS	Isoleucine TRNA Ligase 1, Cytoplasmic	9q22.31	Breast ductal adenocarcinoma
PDE8A	Phosphodiesterase 8A	15q25.3	Melanoma
Long non-coding RNA
H19	H19 Imprinted Maternally Expressed Transcript	11p15.5	Wilms tumor 2, embryonal carcinoma, choriocarcinoma
HOTAIR	HOX Transcript antisense RNA	12q13.13	Gastrointestinal cancers, triple negative breast cancer
HOTTIP	HOXA Transcript At The Distal Tip	7p15.2	Glioma, small cell lung cancer
MALAT1	Metastasis Associated In Lung Adenocarcinoma Transcript 1	11q13.1	Acute monocytic leukemia, ovarian endometrial cancer
PVT1	Plasmacytoma Variant Translocation 1	8q24.21	Plasmacytoma, Hodgkin lymphoma, B-cell lymphoma
PDAC inhibiting	Aliases for Gene(genecards.org)	Gene location (genenames.org/)	Decreased expression in tumorigenesis of other cancers (malacards.org/)
MicroRNA
miR-34a	MicroRNA 34a	1p36.22	Multiple cancers
miR-100	MicroRNA 100	11q24.1	Multiple cancers
miR-217	MicroRNA 217	2p16.1	Chronic lymphocytic leukemia, nasopharyngeal carcinoma
miR-143	MicroRNA 143	5q32	Multiple cancers, incl. PDAC
Long non-coding RNA
GAS5	Growth Arrest Specific 5	1q25.1	Multiple cancers
MEG3	Maternally Expressed 3	14q32.2	Multiple cancers
ENST00000480739	ribosomal protein L13a pseudogene 23	12q13.3	Osteosarcoma

Table 2. Index I and II (whole blood levels) – two diagnostic microRNA panels to distinguish patients with PDAC from healthy controls.^36.

Index I	Index II
miR-145	miR-26b
miR-150	miR-34a
miR-223	miR-122
miR-636	miR-126*
	miR-145
	miR-150
	miR-223
	miR-505
	miR-636
	miR-885.5p

Table 3. miRNAs initially tested in human samples as potential biomarkers for PDAC

Samples tested	Significantly up-regulated	No significant difference	Significantly down-regulated	Potential biomarker for PDAC
PDAC pancreatic juice vs. chronic pancreatitis^Citation35	Ex-miR-21	miR-21		Ex-miR-21
	Ex-miR-155	miR-155		Ex-miR-155
Plasma samples from Chinese PDAC patients vs healthy subjects^Citation37	miR-182-5p		miR-139-5p	miR-182-5p
	miR-4732-5p		miR-23b-3p	miR-4732-5p (late-stage) miR-23b3p

Figure 1. Steps to miRNA profiling

Figure 2. Important considerations necessary in profiling and analyzing circulating miRNAs to find validated cancer biomarkers

Schultz NA, Dehlendorff C, Jensen BV, Bjerregaard JK, Nielsen KR, Bojesen SE, Calatayud D, Nielsen SE, Yilmaz M, Holländer NH, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014 Jan 22-29 311(4):392–404. doi:10.1001/jama.2013.284664.

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Nakamura S, Sadakari Y, Ohtsuka T, Okayama T, Nakashima Y, Gotoh Y, Saeki K, Mori Y, Nakata K, Miyasaka Y, et al. Pancreatic juice exosomal MicroRNAs as biomarkers for detection of pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2019 Jul;26(7):2104–2111. doi:10.1245/s10434-019-07269-z

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Zhu Y, Wang J, Wang F, Yan Z, Liu G, Ma Y, Zhu W, Li Y, Xie L, Bazhin AV, et al. Differential MicroRNA expression profiles as potential biomarkers for pancreatic ductal adenocarcinoma. Biochemistry (Mosc). 2019 May;84(5):575–582. doi:10.1134/S0006297919050122

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