Tumour-stroma ratio and prognosis in gastric adenocarcinoma

Kemi, Niko; Eskuri, Maarit; Herva, A. González; Leppänen, Joni; Huhta, Heikki; Helminen, Olli; Saarnio, Juha; Karttunen, Tuomo J.; Kauppila, Joonas H.

doi:10.1038/s41416-018-0202-y

Cited by 79 publications

(93 citation statements)

References 18 publications

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“…Recently, increasing attention has been focused on the association between tumor microenvironment and the prognosis of cancer, such as breast cancer and gastric adenocarcinoma . It is noticeable that infiltrating immune cells have been associated with tumor growth, invasion and metastasis in some cancers .…”

Section: Introductionmentioning

confidence: 99%

“…6 Recently, increasing attention has been focused on the association between tumor microenvironment and the prognosis of cancer, such as breast cancer 7 and gastric adenocarcinoma. 8 It is noticeable that infiltrating immune cells have been associated with tumor growth, invasion and metastasis in some cancers. 9,10 In accordance with these findings, Ali et al 11 revealed that immune infiltration is associated with clinical prognosis of breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic nomogram based on immune scores for breast cancer patients

et al. 2019

Cancer Medicine

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Background Increased attention has been focused on cancer immunity gene signature. However, the threshold of immune scores to predict disease‐free survival (DFS) and overall survival (OS) in breast cancer has not yet been defined. This study aimed to explore the association of immune scores with prognosis and build a clinical nomogram to predict the survival of patients with breast cancer. Methods A total of 986 subjects were analyzed, and clinicopathological characteristics and immune scores were obtained from the TCGA database. Cox proportional hazards regression model was used to estimate the adjusted hazard ratios ( HR s). Based on results of multivariate analysis, nomograms were built. The models were subjected to bootstrap internal validation. The predictive accuracy and discriminative ability were measured by concordance index (C‐index) and the calibration curve. Results The patients were divided into three subgroups according to their immune scores. We found that compared with patients with low immune scores, those with intermediate and high immune scores had significantly improved DFS ( HR and 95% confidence interval [ CI ]: 0.439 [0.242‐0.799], 0.541 [0.343‐0.855], respectively), whereas only intermediate immune scores significantly indicated better OS ( HR and 95% CI : 0.385 [0.163‐0.910]). The C‐index for DFS and OS prediction was 0.723 (95% CI , 0.661‐0.785) and 0.800 (95% CI , 0.724‐0.877), respectively. The calibration curves for probability of 3‐ and 5‐year DFS showed significant agreement between nomogram predictions and the actual observations. Conclusions High and/or intermediate immune scores are significantly correlated with better DFS and OS in patients with breast cancer. Moreover, the nomograms for predicting prognosis may help to estimate the survival of patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic nomogram based on immune scores for breast cancer patients

et al. 2019

Cancer Medicine

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“…As the stromal proportions were correlated with the expression of the methylation-driven key regulators in the G1 group, they were significantly associated with poor survival in multiple showing poor survival associated with higher tumor-stroma interactions [30][31][32] .…”

Section: Influence Of Tme On the Methylation-driven Key Regulatorsmentioning

confidence: 98%

“…Tumor-stroma interactions in GC are associated with prognosis [30][31][32] and contribute to molecular heterogeneity 21 . Hence, we investigated whether variations of the methylation-driven key regulators were from tumor cells or associated with TME.…”

Section: Tumor Intrinsic Variations Of the Methylation-driven Key Regmentioning

confidence: 99%

“…For example, higher proportion of immune cells in the tumor microenvironment is associated with better survival [23][24][25] and better response to checkpoint blockade immunotherapies [26][27][28] . On the other hand, a higher proportion of stromal cells is associated with worse survival 29 , especially in GC [30][31][32] , and worse response to checkpoint blockade immunotherapies 33 . However, molecular connections of TME with different GC heterogeneities have not been systematically examined.…”

Section: Introductionmentioning

confidence: 99%

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Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

Yoo

Chen

Wang

et al. 2020

Preprint

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Gastric cancer (GC) is a heterogeneous disease of diverse genetic, genomic, and epigenetic alterations. Tumor microenvironment (TME) also contributes to the heterogeneity of GC. To investigate GC heterogeneity, we developed an Integrative Sequential Causality Test (ISCT) to identify key regulators of GC by integrating DNA methylation, copy number variation, and transcriptomic data. Applying ISCT to three GC cohorts containing methylation, CNV and transcriptomic data, 11 common methylation-driven key regulators (ADHFE1, CDO1, CRYAB, FSTL1, GPT, PKP3, PTPRCAP, RAB25, RHOH, SFN, and SORD) were identified. Based on these 11 genes, gastric tumors were clustered into 3 clusters which were associated with known molecular subtypes, Lauren classification, tumor stage, and patient survival, suggesting significance of the methylation-driven key regulators in molecular and histological heterogeneity of GC. We further showed that chemotherapy benefit was different in the 3 GC clusters and varied depending on the tumor stage. Both immune/stromal proportions in TME and tumor cell genomic variations contributed to expression variations of the 11 methylation-driven key regulators and to the GC heterogeneity.

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Tumor purity as a prognosis and immunotherapy relevant feature in gastric cancer

Gong

Zhang

2020

Cancer Medicine

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Tumor microenvironment (TME) has been illustrated their clinic pathological significance in predicting outcomes and therapeutic efficacy by more and more studies. Tumor purity, which reflects the features of TME, is defined as the proportion of cancer cell in the tumor tissue. However, the current staging and prognostic prediction system in gastric cancer (GC) paid little attention to TME. Therefore, we carried out the study to explore the role of tumor purity in GC. We retrospectively collected the clinical and transcriptomic data from four public data sets (n = 1340), GSE15459 , GSE26253 , GSE62254 , and The Cancer Genome Atlas (TCGA). About 34 GC patients from Fudan University Shanghai Cancer Center (FUSCC) were assigned as an independent validation group. Tumor purity was measured by a computational method. Low tumor purity was associated with unfavorable prognosis, upregulated EMT and stemness pathways, more infiltrating of Tregs, M1 and M2 macrophages and a higher expression level of various immune checkpoints and chemokines recruiting immune suppressive cells. Our study indicates low tumor purity in GC was associated with unfavorable prognosis and immune‐evasion phenotype. Further investigations toward tumor purity in GC may contribute to prognosis prediction and the decision of therapy strategies.

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Tumour-stroma ratio and prognosis in gastric adenocarcinoma

Abstract: High proportion of stroma is an independent prognostic factor in both intestinal and diffuse histological subtypes of gastric adenocarcinoma.

Cited by 79 publications

References 18 publications

Prognostic nomogram based on immune scores for breast cancer patients

Prognostic nomogram based on immune scores for breast cancer patients

Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

Tumor purity as a prognosis and immunotherapy relevant feature in gastric cancer

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