US 12,000,003 B2
Platform and sample type independent single sample classifier for treatment decision making in pancreatic ductal adenocarcinoma cancer
Jen Jen Yeh, Chapel Hill, NC (US); Richard Moffitt, Stony Brook, NY (US); and Naim Ur Rashid, Raleigh, NC (US)
Assigned to The University of North Carolina at Chapel Hill, Chapel Hill, NC (US)
Appl. No. 17/601,002
Filed by The University of North Carolina at Chapel Hill, Chapel Hill, NC (US)
PCT Filed Apr. 1, 2020, PCT No. PCT/US2020/026209
§ 371(c)(1), (2) Date Oct. 1, 2021,
PCT Pub. No. WO2020/205993, PCT Pub. Date Oct. 8, 2020.
Claims priority of provisional application 62/827,473, filed on Apr. 1, 2019.
Prior Publication US 2022/0170109 A1, Jun. 2, 2022
Int. Cl. C12Q 1/6886 (2018.01); G16B 25/00 (2019.01); G16B 25/10 (2019.01)
CPC C12Q 1/6886 (2013.01) [G16B 25/00 (2019.02); G16B 25/10 (2019.02); C12Q 2600/106 (2013.01); C12Q 2600/112 (2013.01); C12Q 2600/158 (2013.01)] 6 Claims
 
1. A method for treating a subject diagnosed with pancreatic ductal adenocarcinoma (PDAC), the method comprising:
(a) obtaining nucleic acid expression levels for each of the following genes in a biological sample comprising PDAC cells isolated from the subject: GPR87, KRT6A, BCAR3, PTGES, ITGA3, C16orf74, S100A2, KRT5, REG4, ANXA10, GATA6, CLDN18, LGALS4, DDC, SLC40A1, CLRN3, KRT15, KRT17, TFF1, PLA2G10, CDH17, DCBLD2 and TSPAN8, wherein the nucleic acid expression levels were determined using an amplification, hybridization or sequencing assay on the biological sample;
(b) performing a pair-wise comparison of the nucleic acid expression levels for each gene pair in either Gene Pairs 1-8 or Gene Pairs A-H, wherein Gene Pairs 1-8 and Gene Pairs A-H are as follows:
 
 
 
 GENE GENE GENE
 
 
 PAIR A B Coefficient
 
 
 
 1 GPR87 REG4 1.994
 
 2 KRT6A ANXA10 2.031
 
 3 BCAR3 GATA6 1.618
 
 4 PTGES CLDN18 0.922
 
 5 ITGA3 LGALS4 1.059
 
 6 C16orf74 DDC 0.929
 
 7 S100A2 SLC40A1 2.505
 
 8 KRT5 CLRN3 0.485
 
 A GPR87 REG4 3.413
 
 B KRT6A ANXA10 3.437
 
 C KRT17 LGALS4 2.078
 
 D S100A2 TFF1 2.651
 
 E C16orf74 DDC 0.901
 
 F KRT15 PLA2G10 2.677
 
 G PTGES CDH17 2.911
 
 H DCBLD2 TSPAN8  1.903
 
 
(c) calculating a Raw Score for the biological sample, wherein the calculating comprises:
(i) assigning a value of 1 for each Gene Pair from either Gene Pairs 1-8 or Gene Pairs A-H for which Gene A of the Gene Pair has a higher nucleic acid expression level than Gene B of the Gene Pair, and a value of 0 for each Gene Pair from either Gene Pairs 1-8 or Gene Pairs A-H for which Gene A of the Gene Pair has a lower nucleic acid expression level than Gene B of the Gene Pair;
(ii) multiplying each assigned value by the coefficient listed above for each Gene Pair from either Gene Pairs 1-8 or Gene Pairs A-H to calculate eight individual Gene Pair scores from either Gene Pairs 1-8 or Gene Pairs A-H; and
(iii) adding a sum of the eight individual Gene Pair scores from either Gene Pairs 1-8 or Gene Pairs A-H to a respective baseline effect for either Gene Pairs 1-8 or Gene Pairs A-H to calculate a Raw Score for the biological sample, wherein the respective baseline effect is −6.815 for Gene Pairs 1-8 and −12.414 for Gene Pairs A-H, wherein if the calculated Raw Score is greater than or equal to 0, the tumor subtype is determined to be a basal-like subtype, and if the calculated Raw Score if less than 0, the tumor subtype is determined to be a classical subtype;
(d) administering a treatment to the subject based on the subtype assigned, wherein:
(i) if the assigned subtype is a basal-like subtype, the treatment strategy comprises gemcitabine; and
(ii) if the assigned subtype is a classical subtype, the treatment comprises FOLFIRINOX.