Clinicopathological Features and Increased Expression of Toll-Like Receptor 4 of Gastric Cardia Cancer in a High-Risk Chinese Population

Chen, Guangcan; Xu, Ming; Chen, Jingyao; Hong, Liangli; Lin, Wenting; Zhao, Shukun; Zhang, Guohong; Guo, Dan; Liu, Shuhui

doi:10.1155/2018/7132868

Cited by 15 publications

(12 citation statements)

References 59 publications

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“…Similar studies done on thyroid, lung, breast, cervical and gastric cancer found a similar correlation between TLR4 expression and LN metastasis as well as the tumors' ability to progress and invade (18,(32)(33)(34)(35).…”

Section: Discussionsupporting

confidence: 76%

EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study)

Youssef

Raslan

El‐Sheikh

et al. 2018

Alexandria Dental Journal

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INTRODUCTION: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers with high mortality and morbidity rates. Lymph node (LN) metastasis is one of the most important factors in the treatment and prognosis of patients with OSCC. It reduces the overall survival by nearly half. Toll like receptors (TLRs) are evolutionarily conserved proteins and major type of receptors involved in both innate and adaptive immunities and defense against pathogens. TLR4 was the first member of the TLR family to be discovered. It was verified that TLR4 is expressed in many types of tumors including OSCC. The correlation between the expression of this receptor and the presence of nodal metastasis has been studied. Involvement of TLR4 in the invasion and metastasis potentials may thus suggest the use of this protein as a prognostic marker for OSCC and may provide a new insight in the treatment strategy. OBJECTIVES: The aim of the present study was to assess the expression of TLR4 in the primary tumor of OSCC and correlate it with the lymph node status. MATERIALS AND METHODS: TLR4 expression was calculated in 30 OSCC cases. The specimens were taken from the primary tumor of 15 cases proved to have positive lymph nodes and another 15 cases with negative lymph nodes. Immunohistochemical (IHC) staining was performed using the Labeled Strept-Avidin Biotin complex method (LSAB), using the anti-TLR4 antibody. RESULTS: TLR4 was expressed in the OSCC cases and was significantly higher in cases with positive lymph node metastasis than those without. CONCLUSIONS: TLR4 expression could be used as a prognostic marker for OSCC as an indicator for metastasis.

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Section: Discussionsupporting

confidence: 76%

EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study)

Youssef

Raslan

El‐Sheikh

et al. 2018

Alexandria Dental Journal

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“…According to previous reports, there are significant differences in incidence and prognostic specificity between GCC and NGCC, indicating that they are different tumor entities 5 – 7 . GCC has a poor prognosis and is a serious threat to human health 8 .…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a nomogram to predict the prognosis of patients with gastric cardia cancer

Shi¹,

Xu²,

et al. 2020

Sci Rep

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Our goal was to develop a prognostic nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric cardia cancer (GCC). Patients diagnosed with GCC from 2004 to 2015 were screened from the surveillance, epidemiology, and end results (SEER) database. A nomogram was developed based on the variables associated with oS and cSS using multivariate cox analysis regression models, which predicted 3-and 5-year OS and CSS. The predictive performance of the nomogram was evaluated using the consistency index (C-index), calibration curve and decision curve analysis (DCA), and the nomogram was calibrated for 3-and 5-year OS and CSS. A total of 7,332 GCC patients were identified and randomized into a training cohort (5,231, 70%) and a validation cohort (2,200, 30%). Multivariate Cox regression analysis showed that marital status, race, SEER stage, grade, T stage, N stage, M stage, tumor size, and surgery were independent risk factors for OS and CSS in GCC patients. Based on the multivariate Cox regression results, we constructed prognostic nomograms of OS and CSS. In the training cohort, the C-index for the OS nomogram was 0.714 (95% CI = 0.705-0.723), and the C-index for the CSS nomogram was 0.759 (95% CI = 0.746-0.772). In the validation cohort, the C-index for the OS nomogram was 0.734 (95% CI = 0.721-0.747), while the C-index for the CSS nomogram was 0.780 (95% CI = 0.759-0.801). Our nomogram has better prediction than the nomogram based on TNM stage. In addition, in the training and external validation cohorts, the calibration curves of the nomogram showed good consistency between the predicted and actual 3and 5-year OS and CSS rates. The nomogram can effectively predict OS and CSS in GCC patients, which may help clinicians personalize prognostic assessments and clinical decisions. Gastric cancer is the 6th most common cancer and the 3rd leading cause of tumor-related death worldwide 1. It was reported that there were approximately 27,510 new cases of gastric cancer resulting in 11,140 deaths in the United States in 2019 1. Anatomically, gastric cancer can be divided into gastric cardiac carcinoma (GCC) and non-cardia gastric cancer (NGCC). In recent decades, although the overall incidence of gastric cancer has declined worldwide 2 , the incidence of GCC has increased 3. This may be due to the increased incidence of gastroesophageal reflux disease and obesity 4. According to previous reports, there are significant differences in incidence and prognostic specificity between GCC and NGCC, indicating that they are different tumor entities 5-7. GCC has a poor prognosis and is a serious threat to human health 8. At present, the prognosis of GCC is mainly predicted by the TNM staging system 9. The TNM classification proposed by the American Joint Commission on Cancer (AJCC) is the most widely used staging system, and it is mainly based on tumor invasion (T), regional lymph node (N) and distant metastasis (M) to predict the survival

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“…The etiology of GCC is unclear. Previous reports showed that GCC is different from adenocarcinomas located in the lower esophagus or distal stomach in both epidemiology and biology (7). Gastric cardia cancer is defined as carcinoma in which the epicenter is ≤2 cm below the esophageal-gastric junction (32) in China.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study suggested that TLR4 plays a role in carcinogenesis of Chaoshan GCC (7). However, the expression of MyD88 in GCC and its effects on GCC development remain unknown.…”

mentioning

confidence: 98%

Expression and Significance of MyD88 in Patients With Gastric Cardia Cancer in a High-Incidence Area of China

Chen

Xia

et al. 2020

Front. Oncol.

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Background: Gastric cardia cancer (GCC) arises in the area of the stomach adjoining the esophageal-gastric junction and has unique risk factors. It was suggested that the involvement of Helicobacter pylori is associated with GCC from high-risk population. Myeloid differentiation factor 88 (MyD88) is a crucial adaptor molecule in Toll-like signaling pathway recognizing H. pylori. Its role in GCC has not been elucidated yet. In this study, our purpose is to investigate the expression and significance of MyD88 in GCC tissue. Methods: Expression of MyD88 and nuclear factor κB (NF-κB) p105/p50 and infection of H. pylori were detected by immunohistochemistry in gastric cardia tissue. The correlation of MyD88 expression to NF-κB p105/p50 expression, H. pylori infection, and clinicopathologic characteristics in gastric cardia tissue was analyzed. The involvement of MyD88 in patient prognosis was also analyzed. Results: Our data showed that the expression of MyD88 elevated from normal mucosa to inflammation (p = 0.071). The expression of MyD88 was enhanced in GCC tissues by contrast to non-malignant cardia mucosa (p = 0.025). What's more, overexpression of MyD88 was detected in intestinal-type adenocarcinoma with inflammation. Patients with high MyD88 staining revealed a better differentiation (p = 0.02). MyD88 also positively correlated with NF-κB p105/p50 expression (p = 0.012) in cancer tissue. Expression of MyD88 was increased but not significantly in biopsies with H. pylori infection compared with non-infected biopsies. Multivariate analyses revealed lymph node metastasis but not MyD88 expression was an independent predictor for patient survival. Conclusion: These findings provide pathological evidence that upregulating MyD88 and inducing inflammation might be involved in gastric cardia carcinogenesis in high-risk population. MyD88 plays a role in gastric cardia carcinogenesis with NF-κB pathway activation. Higher MyD88 expression is not a major prognostic determinant in GCC, but it may relate to the tumor cell differentiation.

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Clinicopathological Features and Increased Expression of Toll-Like Receptor 4 of Gastric Cardia Cancer in a High-Risk Chinese Population

Cited by 15 publications

References 59 publications

EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study)

EXPRESSION OF TLR4 IN ORAL SQUAMOUS CELL CARCINOMA AND ITS CORRELATION WITH LYMPH NODE METASTASIS (An Immunohistochemical Study)

Development and validation of a nomogram to predict the prognosis of patients with gastric cardia cancer

Expression and Significance of MyD88 in Patients With Gastric Cardia Cancer in a High-Incidence Area of China

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