Serum screening for detection of high-risk group for early-stage diffuse type gastric cancer in Japanese

Abstract Background. Lung squamous cell carcinoma (LUSC) is one of the subtypes of non-small-cell lung cancer (NSCLC) and accounts for approximately 20 to 30% of all lung cancers.Methods. In this study, we developed an immune-related gene pair index (IRGPI) for early-stage LUSC from 3 public LUSC data sets, including The Cancer Genome Atlas LUSC cohort and Gene Expression Omnibus data sets, and explored whether IRGPI could act as a prognostic marker to identify patients with early-stage LUSC at high risk.Results. IRGPI was constructed by 68 gene pairs consisting of 123 unique immune-related genes from TCGA LUSC cohort. In the derivation cohort, the hazard of death among high-risk group was 10.51 times that of the low-risk group (HR, 10.51; 95%CI, 6.96-15.86; p<0.001). The hazard of death among the high-risk group was 2.26 times that of the low-risk group (HR, 2.26; 95%CI, 1.2-4.25; p=0.009) in the GSE37745 validation cohort and was 3.2 times that of low-risk group (HR, 3.2; 95%CI, 0.98-10.4; p=0.042) in the GSE41271 validation cohort. The infiltrations of CD8+ T cells and T follicular helper cells were lower in the high-risk group, as compared with the low-risk group in the TCGA cohort (6.94% vs 9.63%, p=0.004; 2.15% vs 3%, p=0.002, respectively). The infiltrations of neutrophils, activated mast cells and monocytes were higher in the high-risk group, as compared with the low-risk group in the TCGA cohort (1.63% vs 0.72%, p=0.001; 1.64% vs 1.02%, p=0.007; 0.57% vs 0.35%, p=0.041, respectively).Conclusions. IRGPI is a significant prognostic biomarker for predicting overall survival in early-stage LUSC patients.

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Determination of Additional Surgery after Non-Curative Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Practically Modified Application of the eCura System

Cancers ◽

10.3390/cancers13225768 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5768

Author(s):

Sejin Lee ◽

Jeong Ho Song ◽

Sung Hyun Park ◽

Minah Cho ◽

Yoo Min Kim ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

High Risk ◽

Endoscopic Submucosal Dissection ◽

Treatment Guidelines ◽

Risk Group ◽

Venous Invasion ◽

High Risk Group ◽

Submucosal Dissection ◽

Additional Surgery

Background: Additional surgery after non-curative endoscopic submucosal dissection (ESD) may be excessive as few patients have lymph node metastasis (LNM). It is necessary to develop a risk stratification system for LNM after non-curative ESD, such as the eCura system, which was introduced in the Japanese gastric cancer treatment guidelines. However, the eCura system requires venous and lymphatic invasion to be separately assessed, which is difficult to distinguish without special immunostaining. In this study, we practically modified the eCura system by classifying lymphatic and venous invasion as lymphovascular invasion (LVI). Method: We retrospectively reviewed 543 gastric cancer patients who underwent radical gastrectomy after non-curative ESD between 2006 and 2019. LNM was evaluated according to LVI as well as size >30 mm, submucosal invasion ≥500 µm, and vertical margin involvement, which were used in the eCura system. Results: LNM was present in 8.1% of patients; 3.6%, 2.3%, 7.4%, 18.3%, and 61.5% of patients with no, one, two, three, and four risk factors had LNM, respectively. The LNM rate in the patients with no risk factors (3.6%) was not significantly different from that in patients with one risk factor (2.3%, p = 0.523). Among patients with two risk factors, the LNM rate without LVI was significantly lower than with LVI (2.4% vs. 10.7%, p = 0.027). Among patients with three risk factors, the LNM rate without LVI was lower than with LVI (0% vs. 20.8%, p = 0.195), although not statistically significantly. Based on LNM rates according to risk factors, patients with LVI and other factors were assigned to the high-risk group (LNM, 17.4%) while other patients as a low-risk group (LNM, 2.4%). Conclusions: Modifying the eCura system by classifying lymphatic and venous invasion as LVI successfully stratified LNM risk after non-curative ESD. Moreover, the high-risk group can be simply identified based on LVI and the presence of other risk factors.

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Prognostic Autophagy-Related Model Revealed by Integrating Single-Cell RNA Sequencing Data and Bulk Gene Profiles in Gastric Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.729485 ◽

2022 ◽

Vol 9 ◽

Author(s):

Tianying Tong ◽

Jie Zhang ◽

Xiaoqiang Zhu ◽

Pingping Hui ◽

Zhimin Wang ◽

...

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Single Cell ◽

Rna Sequencing ◽

Immune Checkpoint ◽

Risk Model ◽

Risk Group ◽

High Risk Group ◽

Related Model ◽

Single Cell Rna Sequencing

Autophagy has been associated with tumor progression, prognosis, and treatment response. However, an autophagy-related model and their clinical significance have not yet been fully elucidated. In the present study, through the integrative analysis of bulk RNA sequencing and single-cell RNA sequencing, an autophagy-related risk model was identified. The model was capable of distinguishing the worse prognosis of patients with gastric cancer (GC), which was validated in TCGA and two independent Gene Expression Omnibus cohorts utilizing the survival analysis, and was also independent of other clinical covariates evaluated by multivariable Cox regression. The clinical value of this model was further assessed using a receiver operating characteristic (ROC) and nomogram analysis. Investigation of single-cell RNA sequencing uncovered that this model might act as an indicator of the dysfunctional characteristics of T cells in the high-risk group. Moreover, the high-risk group exhibited the lower expression of immune checkpoint markers (PDCD1 and CTLA4) than the low-risk group, which indicated the potential predictive power to the current immunotherapy response in patients with GC. In conclusion, this autophagy-associated risk model may be a useful tool for prognostic evaluation and will facilitate the potential application of this model as an indicator of the predictive immune checkpoint biomarkers.

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Utilization and outcome of systemic chemotherapy for high-risk early-stage cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e17521 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e17521-e17521

Author(s):

Munetaka Takekuma ◽

Shinya Matsuzaki ◽

Koji Matsuo

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Systemic Chemotherapy ◽

Risk Group ◽

Early Stage ◽

Nodal Metastasis ◽

High Risk Group ◽

Parametrial Invasion ◽

All Cause Mortality ◽

Early Stage Cervical Cancer

e17521 Background: To examine trends and outcomes of systemic chemotherapy for high-risk early-stage cervical cancer. Methods: This retrospective observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2000-2016. Surgically-treated women with stage T1-2 cervical cancer who had high-risk factors (lymph node metastasis and/or parametrial invasion) and received adjuvant therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for chemotherapy use versus external beam with chemotherapy (CCRT). Results: Among 2, 462 women with high-risk factor, 185 (7.5%) received systemic chemotherapy. Utilization of chemotherapy has significantly increased over time in multivariable analysis (adjusted-odds ratio per 1-year increment, 1.06, 95% confidence interval [CI] 1.02-1.09). In weighted models, adjuvant chemotherapy and CCRT had comparable survival among women aged < 40 (hazard ratio [HR] for all-cause mortality 0.73, 95%CI 0.41-1.33), adenocarcinoma or adenosquamous histologies (HR 0.90, 95%CI 0.62-1.32), and high-risk group based on nodal metastasis alone (HR 1.17, 95%CI 0.84-1.62). In contrast, chemotherapy was associated with increased all-cause mortality compared to CCRT among women aged ≥40 (HR 1.57, 95%CI 1.19-2.06), squamous histology (HR 1.63, 95%CI 1.19-2.22), and high-risk group per parametrial invasion alone (HR 1.87, 95%CI 1.09-3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95%CI 1.06-2.52). Conclusions: Utilization of systemic chemotherapy for high-risk early-stage cervical cancer is increasing in the United States. Survival effects of adjuvant chemotherapy varied per patient and tumor factors, and this indication may be limited to those who are < 40 years with non-squamous histology and absence of parametrial invasion.

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Eradication of H. pylori Did Not Improve Abnormal Sonic Hedgehog Expression in the High Risk Group for Gastric Cancer

Digestive Diseases and Sciences ◽

10.1007/s10620-011-1916-3 ◽

2011 ◽

Vol 57 (3) ◽

pp. 643-649 ◽

Cited By ~ 9

Author(s):

Akiko Shiotani ◽

Takahisa Murao ◽

Noriya Uedo ◽

Hiroyasu Iishi ◽

Yoshiyuki Yamanaka ◽

...

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Sonic Hedgehog ◽

Risk Group ◽

High Risk Group ◽

H Pylori

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A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Therapeutic Response of Gastric Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.736682 ◽

2021 ◽

Vol 9 ◽

Author(s):

Shilang Xiao ◽

Xiaoming Liu ◽

Lingzhi Yuan ◽

Fen Wang

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Correlation Analysis ◽

Risk Score ◽

Therapeutic Response ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Biological Processes ◽

Spearman Correlation

Background: Accumulating literature demonstrates that long noncoding RNAs (lncRNAs) are involved in ferroptosis and gastric cancer progression. However, the predictive value of ferroptosis-related lncRNAs for prognosis and therapeutic response is yet to be elucidated in gastric cancer (GC).Method: The transcriptomic data and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The association between ferroptosis-related lncRNAs and ferroptosis regulators was analyzed by Spearman correlation analysis. Then, we established a risk predictive model based on the ferroptosis-related lncRNAs using multivariate Cox regression analysis. Furthermore, we performed correlation analysis for the risk score and characteristics of biological processes, immune landscape, stromal activity, genomic integrity, drug response, and immunotherapy efficacy.Results: We constructed a 17-ferroptosis-related-lncRNA signature via multivariate Cox analysis to divide patients into two groups: low- and high-risk groups. The low-risk group was linked to prolonged overall survival and relapse-free survival. The risk score had good predictive ability to predict the prognosis of GC patients compared with other clinical biomarkers. We found that the high-risk group was associated with activation of carcinogenetic signaling pathways, including stromal activation, epithelial-mesenchymal-transition (EMT) activation, and immune escape through integrated bioinformatics analysis. In contrast, the low-risk group was associated with DNA replication, immune-flamed state, and genomic instability. Additionally, through Spearman correlation analysis, we found that patients in the high-risk group may respond well to drugs targeting cytoskeleton, WNT signaling, and PI3K/mTOR signaling, and drugs targeting chromatin histone acetylation, cell cycle, and apoptosis regulation could bring more benefits for the low-risk group. The high-risk group was associated with poor immunotherapy efficacy.Conclusion: Our study systematically evaluated the role of ferroptosis-related lncRNAs in t tumor microenvironment, therapeutic response, and prognosis of GC. Risk score–based stratification could reflect the characteristic of biological processes, immune landscape, stromal activity, genomic stability, and pharmaceutical profile in GC patients. The ferroptosis-related lncRNA signature could serve as a reliable biomarker to predict prognosis and therapeutic response of patients with GC.

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Characterization of the Prognostic m6A-Related lncRNA Signature in Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.630260 ◽

2021 ◽

Vol 11 ◽

Author(s):

Haixu Wang ◽

Qingkai Meng ◽

Bin Ma

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Prognostic Factor ◽

Risk Group ◽

Pearson Correlation ◽

High Risk Group ◽

Independent Prognostic Factor ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Receptor Interaction

N6-methyladenosine (m6A) is a common form of mRNA modification regulated by m6A RNA methylation regulators and play an important role in the progression of gastric cancer (GC). However, the prognostic role of m6A-related lncRNA in gastric cancer has not been fully explored. This study aims at exploring the biological function and prognostic roles of the m6A-related lncRNA signature in gastric cancer. A total of 800 m6A-related lncRNAs were identified through Pearson correlation analysis between m6A regulators and all lncRNAs. Eleven m6A-related lncRNA signatures were identified through a survival analysis and the Kaplan-Meier (KM) curve analysis results suggest that patients in the low-risk group have a better overall survival (OS) and disease-free survival (DFS) outcome than the high-risk group. Also, the lncRNA signature can serve as an independent prognostic factor for OS and DFS. The gene set enrichment analysis (GSEA) result suggests that patients in the high-risk group were mainly enriched in the ECM receptor interaction, focal adhesion, and cytokine-cytokine receptor interaction pathway, while the low-risk group was characterized by the base excision repair pathway. We further constructed an individualized prognostic prediction model via the nomogram based on the independent prognostic factor for the OS and DFS, respectively. In addition, some candidate drugs aimed at GC risk group differentiation were identified using the Connective Map (CMAP) database. Lastly, four subgroups (C1, C2, C3, and C4) were identified based on the m6A-related lncRNA expression, through a consensus clustering algorithm. Among them, C1 and C2 have a greater likelihood to respond to immune checkpoint inhibitor immunotherapy, suggesting that the C1 and C2 subgroup might benefit from immunotherapy. In conclusion, the m6A-related lncRNA signature can independently predict the OS and DFS of GC and may aid in development of personalized immunotherapy strategies.

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