Construction of an immune-related gene signature for prediction of prognosis in patients with cervical cancer

Mei, Jie; Xing, Yan; Lv, Jinru; Gu, Dawei; Pan, Jiadong; Zhang, Yan; Liu, Jinhui

doi:10.1016/j.intimp.2020.106882

Cited by 33 publications

(29 citation statements)

References 35 publications

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“…Low risk patients significantly benefited from chemotherapeutic and immunotherapeutic treatments. In addition to tumorinfiltrating immune cells, immune-related gene sets such as RIPOR2, DAAM2, SORBS1, and CXCL8 (Mei et al, 2020), or LTA, TFRC, TYK2, DLL4, CSK, JUND, NFATC4, SBDS, FLT1, IL17RD, IL3RA, SDC1, PLAU (Ding et al, 2020), were proposed as prognostic genes to stratify CESC patients. However, neither of these studies took co-expression of immune networks into consideration.…”

Section: Discussionmentioning

confidence: 99%

Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients

Budhwani

Turrell

et al. 2021

Front. Mol. Biosci.

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Background: Limited immunotherapy options are approved for the treatment of cervical cancer and only 10–25% of patients respond effectively to checkpoint inhibition monotherapy. To aid the development of novel therapeutic immune targets, we aimed to explore survival-associated immune biomarkers and co-expressed immune networks in cervical cancer.Methods: Using The Cancer Genome Atlas (TCGA) Cervical Squamous Cell Carcinoma (CESC) data (n = 304), we performed weighted gene co-expression network analysis (WGCNA), and determined which co-expressed immune-related genes and networks are associated with survival probability in CESC patients under conventional therapy. A “Pan-Immune Score” and “Immune Suppression Score” was generated based on expression of survival-associated co-expressed immune networks and immune suppressive genes, which were subsequently tested for association with survival probablity using the TCGA Head Neck Squamous Cell Carcinoma (HNSCC) data (n = 528), representing a second SCC cancer type.Results: In CESC, WGCNA identified a co-expression module enriched in immune response related genes, including 462 genes where high expression was associated with increased survival probability, and enriched for genes associated with T cell receptor, cytokine and chemokine signaling. However, a high level of expression of 43 of the genes in this module was associated with decreased survival probability but were not enriched in particular pathways. Separately, we identified 20 genes associated with immune suppression including inhibitory immune checkpoint and regulatory T cell-related genes, where high expression was associated with increased survival probability. Expression of these 20 immune suppressive genes (represented as “Immune Suppression Score”) was highly correlated with expression of overall survival-associated immune genes (represented as “Pan-Immune Score”). However, high expression of seven immune suppression genes, including TWEAK-R, CD73, IL1 family and TGFb family genes, was significantly associated with decreased survival probability. Both scores also significantly associated with survival probability in HNSCC, and correlated with the previously established “Immunophenoscore.”Conclusion: CESC and HNSCC tumors expressing genes predictive of T cell infiltrates (hot tumors) have a better prognosis, despite simultaneous expression of many immune inhibitory genes, than tumors lacking expression of genes associated with T cell infiltrates (cold tumors) whether or not these tumor express immune inhibitory genes.

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Section: Discussionmentioning

confidence: 99%

Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients

Budhwani

Turrell

et al. 2021

Front. Mol. Biosci.

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“…With LAMP3 also functioning in lysosome, Sig27gene likely affects lysosome biology and mTOR activation. Evidence supports negative impacts on tumorigenesis for the rest of six downregulated genes (Table 5), including FPR3 [71], RAB30 [72], RIPOR2 (FAM65B) [73], PLXNA4 [76,77], MCTP1 [86], and KCNN3 [87]. Collectively, the positive and negative impacts of these 12 genes unknown to PC on tumorigenesis are generally in line with the notion of IQGAP1 negatively associating with PC.…”

Section: Potential Oncogenic Functions Of Sig27gene Component Genesmentioning

confidence: 58%

Effective Prediction of Prostate Cancer Recurrence through the IQGAP1 Network

Lin

Kapoor

et al. 2021

Cancers

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IQGAP1 expression was analyzed in: (1) primary prostate cancer, (2) xenografts produced from LNCaP, DU145, and PC3 cells, (3) tumor of PTEN−/− and TRAMP mice, and (4) castration resistant PC (CRPC) produced by LNCaP xenografts and PTEN−/− mice. IQGAP1 downregulations occurred in CRPC and advanced PCs. The downregulations were associated with rapid PC recurrence in the TCGA PanCancer (n = 492, p = 0.01) and MSKCC (n = 140, p = 4 × 10−6) cohorts. Differentially expressed genes (n = 598) relative to IQGAP1 downregulation were identified with enrichment in chemotaxis, cytokine signaling, and others along with reductions in immune responses. A novel 27-gene signature (Sig27gene) was constructed from these DEGs through random division of the TCGA cohort into a Training and Testing population. The panel was validated using an independent MSKCC cohort. Sig27gene robustly predicts PC recurrence at (hazard ratio) HR 2.72 and p < 2 × 10−16 in two independent PC cohorts. The prediction remains significant after adjusting for multiple clinical features. The novel and robust nature of Sig27gene underlie its great translational potential as a prognostic biomarker to predict PC relapse risk in patients with primary PC.

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“…Moreover, AHR is a differentiation regulator of T cells. AHR combined with transcription factor c-Maf, promote the trans activation of the IL-10 and IL-21 promoters and the production of Tr1 [ 30 ]. Zhang et al [ 31 ] demonstrated that AHR mediated the differentiation of infiltrating T cells in colon cancer, thereby increasing the risk of colon cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the study has shown that AHR is a transcription factor that determines the differentiation of monocytes of mice, and that the activation of AHR promotes the differentiation of monocytes into dendritic cells and interferes with the differentiation of monocytes into macrophages [ 12 ]. The level of immune cell infiltration in the tumor microenvironment is closely related to the survival and prognosis of patients [ 13 ]. Wang et al [ 14 ] evaluated the landscape of tumor infiltrating immune cells as prognostic biomarkers in cervical cancer, which suggested that the level of tumor infiltrating immune cells is a decisive factor in the prognosis of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Aryl hydrocarbon receptor is a prognostic biomarker and is correlated with immune responses in cervical cancer

et al. 2021

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Aryl hydrocarbon receptor (AHR) plays an important role in tumor development. However, its function in cervical cancer has not been fully elucidated. We evaluated the ten genes that are predicted to associate with AHR protein interaction. The comprehensive scores were: CYP1A1, ARNT2, HSP90AA1, ARNT, AIP, PTGES3, HSP90AB1, CYP1B1, ESR1, MAF, respectively. In addition, we showed that levels of AHR and its related genes were correlated with the immune infiltration and expression of immuno-regulators (immunoinhibitors, immunostimulators, MHC molecules) levels in cervical cancer. High expression of AHR, CYP1A1, HSP90AA1, and HSP90AB1 and low expression of ESR1 were negatively correlated with the prognoses of cervical cancer patients. The Cox multivariate regression showed that high expression of AHR ( HR = 1.874, 95% CI = 1.069–3.285, P = 0.028) and CYP1A1 ( HR = 1.822, 95%CI = 1.077–3.080, P = 0.025) were risk factors for prognosis in patients with cervical cancer. IHC results indicated that AHR and CYP1A1 were widely expressed in cervical cancer. These findings suggest that AHR and CYP1A1 may serve as prognostic biomarkers for determining prognosis and immune infiltration in cervical cancer.

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Construction of an immune-related gene signature for prediction of prognosis in patients with cervical cancer

Cited by 33 publications

References 35 publications

Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients

Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients

Effective Prediction of Prostate Cancer Recurrence through the IQGAP1 Network

Aryl hydrocarbon receptor is a prognostic biomarker and is correlated with immune responses in cervical cancer

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