Table 1 Potential biomarkers related to the therapeutic effect of ICIs in GC
From: Mechanisms and biomarkers of immune-related adverse events in gastric cancer
Biomarker | Author | Year | Patient number | Correlation between biomarker and ICIs in GC |
|---|---|---|---|---|
IRGPI | Zhang [60] | 2022 | – | IRGPI can predict the prognosis of GC patients and their response to immunotherapy, and patients with lower IRGPI may benefit more from ICI therapy |
PDPN | Hu [61] | 2020 | 65 | PDPN is significantly associated with M2-type TAM and immune markers of T cell exhaustion, and high PDPN predicts poor survival outcomes, especially in GC patients with Her-2 +  |
ANO9 | Katsurahara [62] | 2021 | 84 | High ANO9 expression is an independent poor prognostic factor in patients with advanced GC, and its depletion reduces the ability to bind to PD-1 by downregulating PD-L2 expression |
CSMD1 | Huang [63] | 2021 | 557 | CSMD1-mut is associated with increased TMB and favorable survival, and may have potential significance in predicting the efficacy of anti-PD-L1 |
mTOR | Cheng [64] | 2022 | 1661 | Mutations in mTOR pathway-related genes are associated with better survival in patients treated with ICI, and are associated with increased expression of TMB and PD1/PD-L1. Including FGFR2, PIK3C3, FGFR4, FGFR1, FGF3, AKT1, mTOR and RPTOR |
MUC16 | Zhang [65] | 2022 | 1139 | MUC16 mutation is associated with better prognosis, including lower LNM rate and higher OS rate. Furthermore, MUC16 mutation status was associated with TMB, microsatellite status |
NOTCH3 | Cui [39] | 2021 | 48 | High NOTCH3 expression was associated with lower CD8 + T cells and higher immunosuppressive cells, and NOTCH3 expression was negatively correlated with TMB, GEP score and IPRES |
OX40 and LAG3 | Ohmura [66] | 2020 | 30 | OX40 and LAG3 are associated with better prognosis in patients with advanced gastric cancer treated with anti-PD-1 therapy |
PRKDC | Tan [67] | 2020 | 34 | PRKDC mutations are significantly associated with TMB in a variety of cancers, and gastric or colon cancer patients with PRKDC mutations are also highly associated with MSI-H |
TP53 | Li [68] | 2020 | 3380 | The anti-tumor immunity of TP53 mutation in STAD was significantly lower than that of TP53 wild type, and TP53 mutation cancer was more likely to have higher TMB and TAL |
FAM score | Li [69] | 2022 | 34 | FAM score is associated with immune-related genomic biomarkers, immune cell infiltration and abnormal immune signaling pathways |
EP300 | Chen [70] | 2021 | – | EP300 mutant cancer has significantly higher TMB in a variety of cancer types, and shows a higher proportion of MIS-H and PD-L1 in colon cancer and gastric cancer. In addition, EP300 mutant cancers responded well to ICIs |
RIPK2 | Song [71] | 2022 | – | High RIPK2 expression is associated with poor prognosis in many cancers. Gene co-expression analysis showed that RIPK2 was positively correlated with the expression of immune checkpoint markers |
circDLG1 | Chen [72] | 2021 | 73 | CircDLG1 was significantly up-regulated in anti-PD-1-resistant GC tissues, and high circDLG1 promoted the proliferation, migration, invasion and immune escape of GC cells |
68Â Ga-FAPI-04 | Rong [73] | 2022 | 21 | High FAP expression is closely related to poor prognosis and immunosuppressive cell infiltration. The high uptake of 68Â Ga-FAPI-04 is associated with the reduced therapeutic efficacy of ICB therapy |
CXCR4 | Xue [74] | 2021 | – | High expression of CXCR4 is positively correlated with advanced stage and grade of gastric cancer, and is associated with poor prognosis |
TM4SF18 | Qin [75] | 2022 | 40 | TM4SF18 is up-regulated in GC tissues and cells and is an independent prognostic factor for GC. The expression level of M4SF19 is negatively correlated with most immune cell marker genes and is associated with many immune cells and immune pathways |
HLA-I | Iwasaki [76] | 2021 | 209 | The degree of CD8 + cell infiltration was significantly reduced in HLA-I deficient tumor regions |
CYT score | Hu [77] | 2021 | 8 | CYT score was positively correlated with the proportion of tumor-infiltrating CD8 + T cells and macrophages, and negatively correlated with the proportion of regulatory T cells. High CYT score showed good prognosis and was associated with PD-1, TMB, EB virus subtype and MSI. Patients who responded to anti-PD-1 therapy had a higher CYT score |
LA | Kumagai [78] | 2022 | – | LA is an active checkpoint of Treg cell function in highly glycolytic TME and can upregulate PD-1 expression |
HRD | Fan [79] | 2020 | 484 | HR gene mutation is associated with increased TMB, MSI, and enhanced immune activity. The overall survival rate of HR mut is significantly higher than that of HR wt in GC |
IL-1R1 | Zhang [80] | 2022 | 409 | High IL-1R1 expression indicates poor prognosis and poor response to ICB. IL-1R1 cultivates an immunosuppressive microenvironment characterized by upregulation of M2 macrophages and depletion of CD8 + T cells |
Helicobacter pylori | Zhang [81] | 2021 | – | Helicobacter pylori-activated immune response improves the prognosis of GC patients by increasing PD-L1 expression and CD3 + T cells |