Biomarker for prediction of immunotherapy outcomes and precision treatment strategies and uses thereof

A method of treating a cancer in a subject in need, comprising

• obtaining a biological sample from the subject;
• determining a level of one or more biomarkers in the biological sample, wherein the one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of AVPI1, BAG1, CPS1, DUSP4, FGA, GLCE, HAL, IRS2, MUC5AC, PDE4D, PTP4A1, RFK, SIK1, TACC2, TESC, and TFF1;
• determining an expression score for each of the one or more biomarkers in the biological sample relative to a reference control;
• determining a mean expression score by averaging the one or more expression scores of the one or more biomarkers;
• and
• administering to the subject a therapeutically effective amount of an immunotherapeutic agent if the mean expression score is lower than a threshold.

A method of treating a cancer in a subject in need, comprising

• obtaining a biological sample from the subject;
• determining a level of a first group of one or more biomarkers, a second group of one or more biomarkers, and a third group of one or more biomarkers in the biological sample, wherein the first group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of AVPI1, BAG1, CPS1, DUSP4, FGA, GLCE, HAL, IRS2, MUC5AC, PDE4D, PTP4A1, RFK, SIK1, TACC2, TESC, and TFF1;
• the second group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of ASCL1, CALCA, CALCB, RET, KLK12, AGXT2L1, BAALC, C1orf95, C8orf56, CELF3, COL25A1, CTNND2, ENO3, ERO1LB, KLK11, KLK13, KLK14, LOC100190940, LOC145837, MTMR7, ODC1, SEC11C, SLC14A2, SLC38A8, UGT3A1, and ZMAT4;
• and the third group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of C1orf116, CISH, FAM184A, FBP1, HOPX, IRX5, KCNK5, LMO3, LPCAT1, MBIP, NKX2-1, PLCH1, PPP1R13B, RPS6KA2, SCNN1B, SELENBP1, SFTPB, SLC34A2, ST3GAL5, STXBP1, TMPRSS2, and WFDC2,
• determining an expression score for each of the one or more biomarkers in the biological sample relative to a reference control;
• determining a first expression score by integrating the expression scores of the one or more biomarkers in the first group, a second expression score by integrating the expression score of the one or more biomarkers in the second group, and a third expression score by integrating the expression score of the one or more biomarkers in the third group;
• and
• administering to the subject a therapeutically effective amount of a proinflammatory inhibitor if the first expression score is higher than a first threshold, the second expression score is lower than a second threshold, and the third expression score is lower than a third threshold.

A method of treating cancer in a subject in need, comprising

• obtaining a biological sample from the subject;
• determining a level of a first group of one or more biomarkers, a second group of one or more biomarkers, and a third group of one or more biomarkers in the biological sample, wherein the first group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of AVPI1, BAG1, CPS1, DUSP4, FGA, GLCE, HAL, IRS2, MUC5AC, PDE4D, PTP4A1, RFK, SIK1, TACC2, TESC, and TFF1;
• the second group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of ASCL1, CALCA, CALCB, RET, KLK12, AGXT2L1, BAALC, C1orf95, C8orf56, CELF3, COL25A1, CTNND2, ENO3, ERO1LB, KLK11, KLK13, KLK14, LOC100190940, LOC145837, MTMR7, ODC1, SEC11C, SLC14A2, SLC38A8, UGT3A1, and ZMAT4;
• and the third group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of C1orf116, CISH, FAM184A, FBP1, HOPX, IRX5, KCNK5, LMO3, LPCAT1, MBIP, NKX2-1, PLCH1, PPP1R13B, RPS6KA2, SCNN1B, SELENBP1, SFTPB, SLC34A2, ST3GAL5, STXBP1, TMPRSS2, and WFDC2,
• determining an expression score for each of the one or more biomarkers in the biological sample relative to a reference control;
• determining a first expression score by integrating the expression scores of the one or more biomarkers in the first group, a second expression score by integrating the expression score of the one or more biomarkers in the second group, and a third expression score by integrating the expression score of the one or more biomarkers in the third group;
• and
• administering to the subject a therapeutically effective amount of a proinflammatory inhibitor if the first expression score is higher than a first threshold, the second expression score is lower than a second threshold, and the third expression score is higher than a third threshold.

A method of treating a cancer in a subject in need, comprising

• obtaining a biological sample from the subject;
• determining a level of a first group of one or more biomarkers and a second group of one or more biomarkers, wherein the first group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of AVPI1, BAG1, CPS1, DUSP4, FGA, GLCE, HAL, IRS2, MUC5AC, PDE4D, PTP4A1, RFK, SIK1, TACC2, TESC, and TFF1 and the second group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of ASCL1, CALCA, CALCB, RET, KLK12, AGXT2L1, BAALC, C1orf95, C8orf56, CELF3, COL25A1, CTNND2, ENO3, ERO1LB, KLK11, KLK13, KLK14, LOC100190940, LOC145837, MTMR7, ODC1, SEC11C, SLC14A2, SLC38A8, UGT3A1, and ZMAT4;
• determining an expression score for each of the one or more biomarkers in the biological sample relative to a reference control;
• determining a first expression score by integrating the expression scores of the one or more biomarkers in the first group and a second expression score by integrating the expression score of the one or more biomarkers in the second group;
• and
• administering to the subject a therapeutically effective amount of a TRAF/cIAP inhibitor if the expression score is higher than a first threshold and the second expression score is higher than a second threshold.

A method of treating a cancer in a subject in need, comprising

• obtaining a biological sample from the subject;
• determining a level of a first group of one or more biomarkers, a second group of one or more biomarkers, and a third group of one or more biomarkers in the biological sample, wherein the first group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of AVPI1, BAG1, CPS1, DUSP4, FGA, GLCE, HAL, IRS2, MUC5AC, PDE4D, PTP4A1, RFK, SIK1, TACC2, TESC, and TFF1;
• the second group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of ASCL1, CALCA, CALCB, RET, KLK12, AGXT2L1, BAALC, C1orf95, C8orf56, CELF3, COL25A1, CTNND2, ENO3, ERO1LB, KLK11, KLK13, KLK14, LOC100190940, LOC145837, MTMR7, ODC1, SEC11C, SLC14A2, SLC38A8, UGT3A1, and ZMAT4;
• and the third group of one or more biomarkers comprise one or more RNAs, or an expression product thereof, of the genes selected from the group consisting of C1orf116, CISH, FAM184A, FBP1, HOPX, IRX5, KCNK5, LMO3, LPCAT1, MBIP, NKX2-1, PLCH1, PPP1R13B, RPS6KA2, SCNN1B, SELENBP1, SFTPB, SLC34A2, ST3GAL5, STXBP1, TMPRSS2, and WFDC2,
• determining a z-score, or similar relative expression score, for each of the one or more biomarkers in the biological sample relative to a reference control;
• determining a first z-score by integrating the z-scores of the one or more biomarkers in the first group, a second z-score by integrating the z-scores of the one or more biomarkers in the second group, and a third z-score by integrating the z-scores of the one or more biomarkers in the third group;
• and
• administering to the subject a therapeutically effective amount of a proinflammatory inhibitor if the first z-score is higher than 0.5, the second z-score is lower than 0.5, and the third z-score is lower than 0;
• administering to the subject a therapeutically effective amount of a checkpoint inhibitor if the first z-score is higher than 0.5, the second z-score is lower than 0.5, and the third z-score is higher than 0;
• or
• administering to the subject a therapeutically effective amount of an inhibitor of TRAF/cIAP if the first z-score is higher than 0.5 and the second z-score is higher than 0.5.