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Supplementary Figure 1. The flow diagram of this work.Supplementary Figure 2. Correlation between GKN2 and the pathological stage of LUAD, LUSC, and STAD patients (GEPIA). Supplementary Figure 3. The comparison of tumor infiltration levels among LUAD, LUSC, and STAD with different somatic copy number alterations for GKN2 gene (TIMER). Supplementary Figure 4. Scatterplots of correlation between GKN2 expression and the expression of gene markers of neutrophils in LUAD, LUSC and STAD (TIMER).Supplementary Table 1. GKN2 expression in cancers vs. normal tissue in Oncomine database.Number of analysisCancerCancer typeP-valueFold changeRank (%)Reference (PMID)1Brain and CNS cancerGlioblastoma vs. Normal0.002-1.7425%158271233Breast cancerInvasive Ductal Breast Carcinoma vs. Normal5.44E-042.3131%17389037??Male Breast Carcinoma vs. Normal6.43E-091.6232%TCGA??Invasive Breast Carcinoma Stroma vs. Normal8.74E-204.5202%184384152Colorectal cancerCecum Adenocarcinoma vs. Normal7.83E-12-1.6755%TCGA??Colon Mucinous Adenocarcinoma vs. Normal2.89E-10-1.5206%TCGA2Esophageal cancerBarrett's Esophagus vs. Normal4.02E-0934.0881%16952561??Esophageal Adenocarcinoma vs. Normal9.43E-084.3579%211520799Gastric cancerDiffuse Gastric Adenocarcinoma vs. Normal5.94E-17-120.5131%?21447720??Gastric Intestinal Type Adenocarcinoma vs. Normal1.41E-08-40.9531%?21447720??Gastric Mixed Adenocarcinoma vs. Normal1.95E-04-56.1734%?21447720??Gastric Adenocarcinoma vs. Normal7.00E-03-95.530?5%?21447720??Gastric Intestinal Type Adenocarcinoma vs. Normal8.45E-10-26.9091%19081245??Gastric Mixed Adenocarcinoma vs. Normal1.80E-05-115.7312%19081245??Diffuse Gastric Adenocarcinoma vs. Normal3.40E-02-5.9189%19081245??Gastric Cancer vs. Normal9.30E-08-5.9821%20965966??Gastric Cancer vs. Normal2.00E-03-38.6384%?211324029Lung cancerSmall Cell Lung Carcinoma vs. Normal1.26E-04-7.7111%11707590??Large Cell Lung Carcinoma vs. Normal2.66E-04-10.7561%11707590??Lung Adenocarcinoma vs. Normal1.60E-06-9.2442%11707590??Squamous Cell Lung Carcinoma vs. Normal9.16E-06-11.4073%11707590??Lung Adenocarcinoma vs. Normal2.44E-20-7.2111%22080568??Lung Adenocarcinoma vs. Normal5.05E-19-12.8921%20421987??Large Cell Lung Carcinoma vs. Normal1.18E-17-32.5011%20421987??Squamous Cell Lung Carcinoma vs. Normal2.47E-22-26.4362%20421987??Lung Adenocarcinoma vs. Normal1.42E-28-11.3262%226138421MyelomaMonoclonal Gammopathy of Undetermined Significance vs. Normal5.58E-06-1.7893%170235741SacromaGastrointestinal Stromal Tumor vs. Normal4.26E-20-346.3651%21447720Supplementary Table 2. Correlation of GKN2 mRNA expression and clinicopathological factors in lung cancer by Kaplan-Meier plotter database.GroupsVariables OS (overall survival)FP (first progression)PPS (post-progression survival)N Hazard ratio P-valueN Hazard ratio P-valueN Hazard ratio P-valueGenderfemale3740.96 (0.69 ? 1.35)0.832530.91 (0.58 ? 1.43)0.69561.77 (0.84 ? 3.75)0.13?male6590.81 (0.66 ? 0.99)0.0443430.85 (0.61 ? 1.19)0.35820.81 (0.47 ? 1.38)0.43Smoking historyexclude those never smoked3000.85 (0.57 ? 1.28)0.452970.95 (0.64 ? 1.41)0.8960.91 (0.55 ? 1.52)0.73?only those never smoked1410.62 (0.27 ? 1.39)0.241410.48 (0.26 ? 0.92)0.023401.47 (0.61 ? 3.56)0.39Histologyadenocarcinoma6720.99 (0.78 ? 1.25)0.914430.69 (0.5 ? 0.95)0.0231151.19 (0.73 ? 1.94)0.49?squamous cell carcinoma2710.94 (0.69 ? 1.28)0.691410.73 (0.44 ? 1.23)0.24201.08 (0.38 ? 3.03)0.88Stage14490.74 (0.54 ? 1.01)0.0583160.74 (0.48 ? 1.16)0.19761.18 (0.65 ? 2.16)0.58?21611.16 (0.74 ? 1.83)0.511251.1 (0.65 ? 1.88)0.73541.22 (0.62 ? 2.4)0.57?3441.33 (0.67 ? 2.65)0.4217--8--AJCC stage T12240.73 (0.49 ? 1.08)0.12541.03 (0.28 ? 3.85)0.9691.25 (0.21 ? 7.53)0.81?21901.19 (0.82 ? 1.74)0.361211.06 (0.58 ? 1.96)0.85391.06 (0.58 ? 1.96)0.44?3290.84 (0.38 ? 1.9)0.682--1--?4230.89 (0.38 ? 2.07)0.797--5--AJCC stage N03240.88 (0.64 ? 1.2)0.421260.93 (0.47 ? 1.87)0.84310.81 (0.36 ? 1.8)0.6?11021.02 (0.62 ? 1.67)0.94511.22 (0.49 ? 3)0.67181.03 (0.31 ? 3.42)0.96?2320.91 (0.44 ? 1.89)0.80--0--AJCC stage M04620.8 (0.62 ? 1.02)0.0711770.84 (0.48 ? 1.46)0.53490.89 (0.46 ? 1.71)0.72?18--0--0--?Treatment groupsonly surgical margins negative2040.54 (0.26 ? 1.13)0.0952040.36 (0.2 ? 0.64)0.00032561.99 (0.94 ? 4.21)0.068?chemotherapy (no)212.38 (0.43 ? 13.07)0.3213.55 (0.94 ? 13.51)0.04790.69 (0.07 ? 7.07)0.75?chemotherapy (yes)340.52 (0.16 ? 1.66)0.26350.95 (0.36 ? 2.49)0.92140.34 (0.08 ? 1.43)0.13“-“ means the analysis cannot preformed due to the small number of samples.Supplementary Table 3. Correlation of GKN2 mRNA expression and clinicopathological factors in gastric cancer by Kaplan-Meier plotter database.GroupsVariablesOS (overall survival)FP (first progression)PPS (post-progression survival)N Hazard ratio P-valueN Hazard ratio P-valueN Hazard ratio P-valueGenderfemale1870.82 (0.54 ? 1.26)0.371790.94 (0.62 ? 1.43)0.791270.65 (0.4 ? 1.07)0.088?male3490.71 (0.53 ? 0.95)0.023410.69 (0.51 ? 0.92)0.0112560.67 (0.48 ? 0.93)0.017Perforationno1690.94 (0.63 ? 1.4)0.761690.89 (0.61 ? 1.3)0.55670.96 (0.57 ? 1.64)0.89?yes4--4--2--HER2 statusnegative4290.86 (0.66 ? 1.12)0.263560.75 (0.56 ? 1)0.0472830.74 (0.53 ? 1.03)0.074?positive2020.78 (0.54 ? 1.13)0.191660.73 (0.48 ? 1.1)0.141010.53 (0.32 ? 0.87)0.011Stage1621.64 (0.54 ? 5.02)0.38601.67 (0.55 ? 5.12)0.36311.24 (0.28 ? 5.59)0.77?21350.81 (0.44 ? 1.52)0.521311.03 (0.57 ? 1.87)0.931050.75 (0.39 ? 1.44)0.38?31970.59 (0.41 ? 0.87)0.00641860.55 (0.38 ? 0.8)0.00151420.6 (0.39 ? 0.92)0.018?41400.89 (0.6 ? 1.32)0.561410.88 (0.6 ? 1.29)0.521040.93 (0.6 ? 1.45)0.75Stage T114--14--3--?22410.81 (0.53 ? 1.24)0.342391 (0.66 ? 1.51)0.991960.76 (0.48 ? 1.18)0.22?32040.59 (0.42 ? 0.84)0.00282040.65 (0.46 ? 0.91)0.0111500.62 (0.42 ? 0.92)0.016?4381.08 (0.47 ? 2.45)0.86390.77 (0.36 ? 1.66)0.51291.38 (0.56 ? 3.44)0.48Stage N0741.01 (0.44 ? 2.29)0.99721.04 (0.46 ? 2.37)0.92410.79 (0.25 ? 2.45)0.68?1+2+34220.64 (0.49 ? 0.84)0.000914230.69 (0.53 ? 0.88)0.00343370.65 (0.49 ? 0.87)0.0033?12250.57 (0.38 ? 0.87)0.00792220.64 (0.43 ? 0.96)0.0271690.56 (0.35 ? 0.88)0.011?21210.6 (0.38 ? 0.94)0.0251250.68 (0.44 ? 1.04)0.0761050.65 (0.41 ? 1.05)0.077?3760.71 (0.42 ? 1.21)0.2760.65 (0.38 ? 1.1)0.11630.86 (0.49 ? 1.53)0.61Stage M04440.58 (0.44 ? 0.77)0.000134430.66 (0.51 ? 0.86)0.00223420.64 (0.47 ? 0.86)0.0032?1561.47 (0.81 ? 2.68)0.21562.09 (1.14 ? 3.83)0.016360.56 (0.27 ? 1.17)0.12Lauren classificationinstestinal2690.76 (0.53 ? 1.08)0.132630.77 (0.54 ? 1.1)0.151920.69 (0.46 ? 1.05)0.08?diffuse2400.65 (0.46 ? 0.92)0.0142310.72 (0.51 ? 1.01)0.0591760.57 (0.39 ? 0.84)0.004?mixed293.34 (1 ? 11.2)0.039284.31 (1.44 ? 12.87)0.004716--Differentiationpoorly differentiated1210.64 (0.39 ? 1.04)0.0671210.6 (0.38 ? 0.96)0.029491.12 (0.59 ? 2.13)0.72?moderately differentiated671.78 (0.92 ? 3.43)0.082671.49 (0.8 ? 2.79)0.2241.52 (0.62 ? 3.74)0.36?well differentiated5--5--0--Treatmentsurgery alone3800.81 (0.61 ? 1.08)0.163750.9 (0.69 ? 1.19)0.482770.74 (0.55 ? 1.02)0.062?5 FU based adjuvant340.2 (0.07 ? 0.58)0.0014340.15 (0.05 ? 0.44)0.00011211.29 (0.47 ? 3.49)0.62?other adjuvant760.22 (0.07 ? 0.66)0.0029640.42 (0.18 ? 0.97)0.037740.31 (0.1 ? 0.94)0.029“-“ means the analysis cannot preformed due to the small number of samples.Supplementary Table 4. The cox proportional hazard model of GKN2 and six tumor-infiltrating immune cells in LUAD, LUSC and STAD (TIMER).Surv(LUAD)?coefHR95%CI_l95%CI_up.valuesigB_cell-5.3050.00500.0640***CD8_Tcell0.5011.650.2769.8650.583?CD4_Tcell2.74115.4981.103217.80.042*Macrophage0.1181.1250.08614.7760.929?Neutrophil-0.7990.450.0120.4410.682?Dendritic-0.2020.8170.2193.0560.764?GKN2-0.0380.9630.9051.0240.224?Surv(LUSC)?coefHR95%CI_l95%CI_up.valuesigB_cell0.5761.7790.16718.990.633?CD8_Tcell-1.0970.3340.0611.8370.207?CD4_Tcell0.2861.3310.12214.5080.815?Macrophage-1.7520.1730.0142.1940.176?Neutrophil1.1363.1130.13571.9370.478?Dendritic0.5451.7250.4346.8640.439?GKN20.1551.1671.0361.3150.011*Surv(STAD)?coefHR95%CI_l95%CI_up.valuesigB_cell3.18524.1610.351666.6680.14?CD8_Tcell-2.0420.130.0091.9680.141?CD4_Tcell-3.8080.02201.7980.089?Macrophage5.688295.38816.0655431.2450***Neutrophil-0.6660.5140.00387.4570.799?Dendritic1.4964.4640.39450.5360.227?GKN20.0041.0040.9521.0590.874?*P < 0.05; **P < 0.01; ***P < 0.001.Supplementary Table 5. Correlation analysis between GKN2 and immune relate genes of monocytes and macrophages in LUAD, LUSC and STAD (GEPIA).DescriptionGene markersLUADLUSCSTADTumorTumorTumorRP-valueRP-valueRP-valueNeutrophilsMPO ?0.0280.540.29***0.1*PTPRC(CD45R)0.13**0.29***0.2***FUT4 (CD15)-0.0550.230.0320.480.0530.28MonocytesCD14?0.0380.40.22***0.00720.88?CD360.41***0.45***0.18**? ITGAM (CD11B）0.0190.670.24***0.12*TAMs (tumor-associated macrophages)CD680.1*0.27***0.1*?CCL20.0180.690.23***0.0110.82?CSF1R0.0130.770.29***0.1* M1 macrophages NOS2 (NOS2A)0.14**0.0840.063?0.00570.91?CXCL10?0.19***0.00840.85?0.0580.24?TNF?0.0470.30.11*0.13**M2 macrophagesCCL180.3***0.43***0.0180.72?CD1630.093*0.37***?0.0410.41? IL10 (CSIF)0.11*0.3***0.0530.29Tumor, correlation analysis in tumor tissue of TCGA. R, p-value from Spearman's test. *P < 0.05; **P < 0.01; ***P < 0.001. ................
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