Determination of jak-stat3 pathway activity using unique combination of target genes

A computer program product for determining the activity level of a JAK-STAT3 cellular signaling pathway in a subject comprising:

• a. a non-transitory computer readable storage medium having computer readable program code embodied therewith, the computer readable program code executable by at least one processor to:
• i. calculate an activity level of a JAK-STAT3 transcription factor element in a sample isolated from a subject, wherein the activity level of the JAK-STAT3 transcription factor element in the sample is associated with JAK-STAT3 cellular signaling, and wherein the activity level of the JAK-STAT3 transcription factor element in the sample is calculated by:
• 1. receiving data on the expression levels of at least three target genes derived from the sample, wherein the at least three target genes are selected from BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, or from BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1;
• 2. calculating the activity level of the JAK-STAT3 transcription factor element in the sample using a calibrated pathway model, wherein the calibrated pathway model compares the expression levels of the at least three target genes in the sample with expression levels of the at least three target genes in the calibrated pathway model which define an activity level of the JAK-STAT3 transcription factor element;
• and,
• ii. calculate the activity level of the JAK-STAT3 cellular signaling pathway in the sample based on the calculated activity level of the JAK-STAT3 transcription factor element in the sample.

A method of treating a subject suffering from a disease associated with an activated JAK-STAT3 cellular signaling pathway comprising:

• a. receiving information regarding the activity level of a JAK-STAT3 cellular signaling pathway derived from a sample isolated from the subject, wherein the activity level of the JAK-STAT3 cellular signaling pathway is determined by:
• i. calculating an activity level of a JAK-STAT3 transcription factor element in a sample isolated from the subject, wherein the activity level of the JAK-STAT3 transcription factor element in the sample is associated with JAK-STAT3 cellular signaling, and wherein the activity level of the JAK-STAT3 transcription factor element in the sample is calculated by:
• 1. receiving data on the expression levels of at least three target genes derived from the sample, wherein the JAK-STAT3 transcription factor element controls transcription of the at least three target genes, and wherein the at least three target genes are selected from BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, or from BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1;
• 2. calculating the activity level of the JAK-STAT3 transcription factor element in the sample using a calibrated pathway model, wherein the calibrated pathway model compares the expression levels of the at least three target genes in the sample with expression levels of the at least three target genes in the calibrated pathway model which define an activity level of JAK-STAT3 transcription factor element;
• and,
• ii. calculating the activity level of the JAK-STAT3 cellular signaling pathway in the sample based on the calculated activity level of the JAK-STAT3 transcription factor element in the sample;
• and,
• b. administering to the subject a JAK-STAT3 inhibitor if the information regarding the activity level of the JAK-STAT3 cellular signaling pathway is indicative of an active JAK-STAT3 cellular signaling pathway.

A kit for measuring expression levels of JAK-STAT3 cellular signaling pathway target genes comprising:

• a. a set of polymerase chain reaction primers directed to at least six JAK-STAT3 cellular signaling pathway target genes derived from a sample isolated from a subject;
• and
• b. a set of probes directed to the at least six JAK-STAT3 cellular signaling pathway target genes;
• wherein the at least six target genes are selected from BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, or from BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1.

A kit for determining the activity level of a JAK-STAT3 cellular signaling pathway in a subject comprising:

• a. one or more components capable of identifying expression levels of at least three JAK-STAT3 cellular signaling pathway target genes derived from a sample of the subject, wherein the at least three target genes are selected from BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, or from BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1;
• and,
• b. optionally, a non-transitory computer readable storage medium having computer readable program code embodied therewith, the computer readable program code executable by at least one processor to:
• i. calculate an activity level of a JAK-STAT3 transcription factor element in the sample, wherein the activity level of the JAK-STAT3 transcription factor element in the sample is associated with JAK-STAT3 cellular signaling, and wherein the activity level of the JAK-STAT3 transcription factor element in the sample is calculated by:
• 1. receiving data on the expression levels of the at least three target genes derived from the sample;
• 2. calculating the activity level of the JAK-STAT3 transcription factor element in the sample using a calibrated pathway model, wherein the calibrated pathway model compares the expression levels of the at least three target genes in the sample with expression levels of the at least three target genes in the calibrated pathway model which define an activity level of the JAK-STAT3 transcription factor element;
• and,
• ii. calculate the activity level of the JAK-STAT3 cellular signaling pathway in the sample based on the calculated activity level of the JAK-STAT3 transcription factor element in the sample.