US2022127676A1PendingUtilityA1
Methods and compositions for prognostic and/or diagnostic subtyping of pancreatic cancer
Assignee: UNIV NORTH CAROLINA CHAPEL HILLPriority: Oct 14, 2014Filed: Jun 2, 2021Published: Apr 28, 2022
Est. expiryOct 14, 2034(~8.2 yrs left)· nominal 20-yr term from priority
G01N 33/57525C12Q 2600/158C12Q 2600/112G16B 25/00C12Q 2600/156G16H 50/20G16B 25/10C12Q 2600/106G01N 2800/52C12Q 1/6886C12Q 2600/118G01N 33/57438
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Claims
Abstract
Methods for generating a prognostic and/or subtype signature for a subject with pancreatic ductal adenocarcinoma (PDAC) are provided. In some embodiments, the methods include determining expression levels for one or more genes listed in Tables 2-5, 9, 10, or 11, and/or the DE-S and/or DE-T subset of genes in PDAC cells obtained from the subject, wherein the determining provides a prognostic and/or subtype signature for the subject. Also provided are methods for classifying a subject diagnosed with pancreatic ductal adenocarcinoma (PDAC) as having an activated stroma subtype or a normal stroma subtype of PDAC and/or a basal subtype or a classical subtype of PDAC; and methods for identifying a differential treatment strategy for a subject diagnosed with pancreatic ductal adenocarcinoma (PDAC).
Claims
exact text as granted — not AI-modified1 .- 14 . (canceled)
15 . A method of assaying a biological sample obtained from a subject comprising measuring a nucleic acid expression level of gene A and gene B for a plurality of gene pairs selected from the group consisting of Table 9, 10 and 11 in the biological sample obtained from the subject, wherein the subject has been diagnosed a cancer.
16 . The method of claim 15 , wherein the cancer is selected from the group consisting of pancreatic cancer, breast cancer and bladder cancer and the biological samples is obtained from the pancreas, the breast or the bladder, respectively.
17 . The method of claim 16 , wherein the plurality of gene pairs are selected from Table 9.
18 . The method of claim 17 , wherein the plurality of gene pairs selected from Table 9 comprises all of the gene pairs from Table 9.
19 . The method of claim 16 , wherein the cancer is pancreatic cancer and the biological samples is obtained from the pancreas.
20 . The method of claim 19 , wherein the plurality of gene pairs are selected from Table 10 and 11.
21 . The method of claim 20 , wherein the plurality of gene pairs selected from Table 10 comprises all of the gene pairs from Table 10.
22 . The method of claim 20 , wherein the plurality of gene pairs selected from Table 11 comprises all of the gene pairs from Table 11.
23 . The method of claim 15 , wherein the subject is a human.
24 . A method for treating cancer in a subject diagnosed with cancer, the method comprising:
(a) measuring a nucleic acid expression level of gene A and gene B for a plurality of gene pairs selected from Table 9 in a biological sample obtained from the subject, wherein the subject has been diagnosed with either breast cancer, pancreatic cancer or bladder cancer; (b) classifying the subject as having a basal subtype of the cancer based on the nucleic acid expression levels of gene A and gene B in each gene pair from the plurality of gene pairs selected from Table 9, wherein the classifying comprises calculating a value d using EQUATION 1,
P
i
=
{
1
if
A
i
>
B
i
0
if
B
i
≥
A
i
d
=
I
+
∑
i
P
i
C
i
decision
=
{
Basal
if
d
>
0
Not
Basal
if
d
≤
0
EQUATION
1
wherein A i and B i are measured expression levels of each Gene A and each Gene B of Table 9 in the i th row, respectively, C i is the i th coefficient, and I is the intercept, and further wherein if d is greater than 0, the subject is classified as having a basal subtype, and if d is less than or equal to 0, the subject is classified as having a not basal subtype; and
(c) administering a treatment for the subject based on the subject being classified as having a basal subtype, wherein the treatment is selected from agents for treating the basal subtype listed in FIG. 20 , agents for treating the basal subtype listed in FIG. 21 , agents listed in Table 4, agents listed in Table 6 and combinations thereof.
25 . The method of claim 24 , wherein the plurality of gene pairs selected from Table 9 comprises all of the gene pairs from Table 9.
26 . A method for treating pancreatic cancer in a subject diagnosed with pancreatic cancer, the method comprising:
(a) measuring a nucleic acid expression level of gene A and gene B for a plurality of gene pairs selected from Table 10 or Table 11 in a biological sample comprising pancreatic cells obtained from the subject; (b) classifying the subject as having a normal stroma subtype of pancreatic cancer or an activated stroma subtype of pancreatic cancer based on the nucleic acid expression levels of gene A and gene B in each gene pair from the plurality of gene pairs selected from Table 10, wherein the classifying comprises calculating a value d using EQUATION 2,
P
i
=
{
1
if
A
i
>
B
i
0
if
B
i
≥
A
i
d
=
I
+
∑
i
P
i
C
i
decision
=
{
Activated
Stroma
if
d
>
0
Normal
Stroma
if
d
≤
0
EQUATION
2
wherein A i and B i are measured expression levels of each Gene A and each Gene B of the plurality of gene pairs selected from Table 10 in the i th row, respectively, C i is the i th coefficient, and I is the intercept, and further wherein if d is greater than 0, the subject is classified as having an activated stroma subtype, and if d is less than or equal to 0, the subject is classified as having a normal stroma subtype OR
classifying the subject as having a basal-like subtype of pancreatic cancer or a classical subtype of pancreatic cancer based on the nucleic acid expression levels of gene A and gene B in each gene pair from the plurality of gene pairs selected from Table 11, wherein the classifying comprises calculating a value d using EQUATION 3,
P
i
=
{
1
if
A
i
>
B
i
0
if
B
i
≥
A
i
d
=
I
+
∑
i
P
i
C
i
decision
=
{
Basal
-
like
if
d
>
0
Classical
if
d
≤
0
EQUATION
3
wherein A i and B i are measured expression levels of each Gene A and each Gene B of the plurality of gene pairs selected from Table 11 in the i th row, respectively, C i is the i th coefficient, and I is the intercept, and further wherein if d is greater than 0, the subject is classified as having a basal-like subtype, and if d is less than or equal to 0, the subject is classified as having a classical subtype; and
(c) administering a treatment for the subject based on the subject being classified as having a normal stroma subtype, an activated stroma subtype, a basal-like subtype or a classical subtype, wherein the treatment for the normal stroma subtype is surgery alone or surgery prior to treatment with agents selected from the agents listed in Table 3, wherein the treatment for the activated stroma subtype is selected from the groups consisting of radiation, stroma modulation therapies noted in FIG. 20 and agents listed in or directed against the genes listed in Table 2, wherein the treatment for the basal-like subtype is cisplatin, oxaliplatin-based therapies, gemcitabine, chemotherapy with the agents listed in FIG. 20 and/or with agents listed in Tables 4 and 6 and/or against the genes listed in Tables 4 and 6, and wherein the treatment for the classical subtype is 5-fluorouracil, platinum-based therapy, surgery or prior to surgery, treatment with one or more agents listed in Table 5 or Table 6 or directed against the genes listed in Tables 5 and 6.
27 . The method of claim 26 , wherein the plurality of gene pairs selected from Table 10 comprises all of the gene pairs from Table 10.
28 . The method of claim 26 , wherein the plurality of gene pairs selected from Table 11 comprises all of the gene pairs from Table 11.Join the waitlist — get patent alerts
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