PO-509 CD44V6 is a marker of poor prognosis and has potential as predictive marker of response to conventional chemotherapy in gastric cancer

AbstractLate diagnosis, modest treatment options and lack of predictive markers of therapy response dictate the poor overall survival (OS) of ∼1 year in most gastric cancer (GC) patients. We hypothesized that the level of CD44v6 expression in tumor cells could predict therapy response and prognosis in GC patients.We analyzed a surgical tumor series of GC patients for the extension of CD44v6 membranous immuno-expression, clinical-pathological features, patient survival, and response to therapy. By integrating this information, we assessed the value of CD44v6 expression to predict benefit from current treatment regimens and prognosis in GC patients. We used GC cell lines and mouse xenografts to assess and/validate the biological impact of CD44v6 expression in GC cells behavior.We demonstrated that GC patients whose tumors present higher levels of CD44v6 membranous expression benefit from adding chemotherapy to surgery as opposed to those without CD44v6 expression. Moreover, patients bearing CD44_high tumors presented worse OS than those bearing CD44_absent/low tumors, consolidating the role of CD44v6 expression as an independent factor of poor prognosis in this disease. Finally, ourin vitroand patients’ data pinpoints the CD44v6+ cell population as the driver of tumor recurrence following conventional chemotherapy, in heterogeneous tumors composed by CD44v6- and CD44v6+ cells.Our study pioneers the identification of CD44v6 as a potential predictive marker of response to conventional chemotherapy, and consolidates CD44v6 as an independent marker of poor prognosis in GC. Overall, our data strongly supports selection of patients with high CD44v6 expressing tumors for conventional chemotherapy with or without surgery, regardless of the TNM stage.

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Disseminated tumor cells in the blood of patients with gastric cancer are an independent predictive marker of poor prognosis

Scandinavian Journal of Gastroenterology ◽

10.1080/00365520510015557 ◽

2005 ◽

Vol 40 (7) ◽

pp. 843-849 ◽

Cited By ~ 28

Author(s):

Bertram Illert ◽

Martin Fein ◽

Christoph Otto ◽

Florian Cording ◽

Dominik Stehle ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Cells ◽

Poor Prognosis ◽

Predictive Marker ◽

Disseminated Tumor Cells

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CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients

Biomedicines ◽

10.3390/biomedicines9091249 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1249

Author(s):

Gabriela M Almeida ◽

Carla Pereira ◽

Ji-Hyeon Park ◽

Carolina Lemos ◽

Sofia Campelos ◽

...

Keyword(s):

Gastric Cancer ◽

Therapy Response ◽

Predictive Marker ◽

Response To Treatment ◽

Depth Of Invasion ◽

Conventional Chemotherapy ◽

Tumor Expression ◽

Gastric Cancer Patients ◽

Selection Of ◽

Cd44v6 Expression

In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002–2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and -negative populations (CD44v6_3+) (p < 0.007 and p < 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.

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Severe Loss of Visceral Fat and Skeletal Muscle After Chemotherapy Predict Poor Prognosis in Metastatic Gastric Cancer Patients Without Gastrectomy

SSRN Electronic Journal ◽

10.2139/ssrn.3391371 ◽

2019 ◽

Author(s):

Wanjing Feng ◽

Mingzhu Huang ◽

Xiaoying Zhao ◽

Siyuan Chen ◽

Chenchen Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Skeletal Muscle ◽

Cancer Patients ◽

Visceral Fat ◽

Poor Prognosis ◽

Metastatic Gastric Cancer ◽

Severe Loss ◽

Gastric Cancer Patients

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Identification of novel autoantibodies in ascites of relapsed paclitaxel-resistant gastric cancer with peritoneal metastasis using immunome protein microarrays and proteomics

Cancer Biomarkers ◽

10.3233/cbm-203142 ◽

2021 ◽

pp. 1-10

Author(s):

Zhongyin Yang ◽

Chao Yan ◽

Wentao Liu ◽

Wei Xu ◽

Chen Li ◽

...

Keyword(s):

Gastric Cancer ◽

Effective Treatment ◽

Peritoneal Metastasis ◽

Quantitative Proteomics ◽

Poor Prognosis ◽

Protein Microarrays ◽

Tandem Mass ◽

Tandem Mass Tag ◽

Resistant Group ◽

Potential Biomarkers

BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis usually have extremely poor prognosis. Intraperitoneal infusion of paclitaxel (PTX) provides an effective treatment, but relapse and PTX-resistance are unavoidable disadvantages, and it is difficult to monitor the occurrence of PTX-resistance. OBJECTIVE: The aim of this study was to explore novel autoantibodies in the ascites of individuals with relapsed PTX-resistant GC with peritoneal metastasis. METHODS: Ascites samples were collected before PTX infusion and after the relapse in 3 GC patients. To determine the expression of significantly changed proteins, we performed autoantibody profiling with immunome protein microarrays and tandem mass tag (TMT) quantitative proteomics, and then, the overlapping proteins were selected. RESULTS: Thirty-eight autoantibodies that were differentially expressed between the ascites in the untreated group and relapsed PTX-resistant group were identified. For confirmation of the results, TMT quantitative proteomics was performed, and 842 dysregulated proteins were identified. Four proteins, TPM3, EFHD2, KRT19 and vimentin, overlapped between these two assays. CONCLUSIONS: Our results first revealed that TPM3, EFHD2, KRT19 and vimentin were novel autoantibodies in the ascites of relapsed PTX-resistant GC patients. These autoantibodies may be used as potential biomarkers to monitor the occurrence of PTX-resistance.

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LAMB1 Is Related to the T Stage and Indicates Poor Prognosis in Gastric Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211004944 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110049

Author(s):

Tao Ran ◽

ZhiJi Chen ◽

LiWen Zhao ◽

Wei Ran ◽

JinYu Fan ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

Hazard Models ◽

Proportional Hazard ◽

Kegg Analysis ◽

Proportional Hazard Models ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

Cox Proportional Hazard Models ◽

Gastric Cancer Patients

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.

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Gastric cancer with repeated metastasis in the colonic lumen: a case report and multi-surgical experience

Journal of International Medical Research ◽

10.1177/03000605211018420 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052110184

Author(s):

Yi Wang ◽

Peiqing Ma ◽

Kan Liu ◽

Dongkui Xu ◽

Qian Liu

Keyword(s):

Gastric Cancer ◽

Gastric Carcinoma ◽

Poor Prognosis ◽

Partial Gastrectomy ◽

Radical Resection ◽

Surgical Experience ◽

Colonic Lumen ◽

Poorly Differentiated ◽

Gastric Stump Carcinoma ◽

Peritoneal Spread

Poorly differentiated gastric adenocarcinoma is commonly associated with lymph node metastasis, peritoneal spread, and liver metastasis but rarely with intraintestinal metastasis. Most patients with metastatic gastric carcinoma are unable to undergo surgical treatment and have a poor prognosis. A 42-year-old man with hunger-related abdominal pain was diagnosed as having gastric cancer. After the first surgery (distal partial gastrectomy) and the second surgery (gastric stump carcinoma (GSC) resection), the patient suffered repeated multiple intracolonic metastases and underwent three additional resection operations. The patient survived for 154 months after the first operation. In patients with gastric carcinoma that metastasizes to the colonic lumen, radical resection, if possible, can extend survival. Once patients develop extensive extraintestinal metastasis, radical resection cannot be performed, and patients often exhibit a poor prognosis.

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Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer

Journal of Gastrointestinal Cancer ◽

10.1007/s12029-020-00563-0 ◽

2021 ◽

Author(s):

Javad Farhadi ◽

Ladan Goshayeshi ◽

Alireza Motavalizadehkakhky ◽

Jamshid Mehrzad ◽

Hassan Mehrad-Majd

Keyword(s):

Gastric Cancer ◽

Poor Prognosis

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Clinical and prognostic significances of cancer stem cell markers in gastric cancer patients: a systematic review and meta-analysis

Cancer Cell International ◽

10.1186/s12935-021-01840-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mahdieh Razmi ◽

Roya Ghods ◽

Somayeh Vafaei ◽

Maryam Sahlolbei ◽

Leili Saeednejad Zanjani ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Clinical Outcomes ◽

Cancer Progression ◽

Poor Prognosis ◽

Meta Analysis ◽

Disease Free Survival ◽

Stem Cell Markers ◽

Free Survival

Abstract Background Gastric cancer (GC) is considered one of the most lethal malignancies worldwide, which is accompanied by a poor prognosis. Although reports regarding the importance of cancer stem cell (CSC) markers in gastric cancer progression have rapidly developed over the last few decades, their clinicopathological and prognostic values in gastric cancer still remain inconclusive. Therefore, the current meta-analysis aimed to quantitatively re-evaluate the association of CSC markers expression, overall and individually, with GC patients’ clinical and survival outcomes. Methods Literature databases including PubMed, Scopus, ISI Web of Science, and Embase were searched to identify the eligible articles. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded or calculated to determine the relationships between CSC markers expression positivity and overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS), disease-specific survival (DSS)/ cancer-specific survival (CSS), and clinicopathological features. Results We initially retrieved 4,425 articles, of which a total of 66 articles with 89 studies were considered as eligible for this meta-analysis, comprising of 11,274 GC patients. Overall data analyses indicated that the overexpression of CSC markers is associated with TNM stage (OR = 2.19, 95% CI 1.84–2.61, P = 0.013), lymph node metastasis (OR = 1.76, 95% CI 1.54–2.02, P < 0.001), worse OS (HR = 1.65, 95% CI 1.54–1.77, P < 0.001), poor CSS/DSS (HR = 1.69, 95% CI 1.33–2.15, P < 0.001), and unfavorable DFS/RFS (HR = 2.35, 95% CI 1.90–2.89, P < 0.001) in GC patients. However, CSC markers expression was found to be slightly linked to tumor differentiation (OR = 1.25, 95% CI 1.01–1.55, P = 0.035). Sub-analysis demonstrated a significant positive relationship between most of the individual markers, specially Gli-1, Oct-4, CD44, CD44V6, and CD133, and clinical outcomes as well as the reduced survival, whereas overexpression of Lgr-5, Nanog, and sonic hedgehog (Shh) was not found to be related to the majority of clinical outcomes in GC patients. Conclusion The expression of CSC markers is mostly associated with worse outcomes in patients with GC, both overall and individual. The detection of a combined panel of CSC markers might be appropriate as a prognostic stratification marker to predict tumor aggressiveness and poor prognosis in patients with GC, which probably results in identifying novel potential targets for therapeutic approaches.

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