TLR3 expression status predicts prognosis in patients with advanced thoracic esophageal squamous cell carcinoma after esophagectomy

Sato, Yusuke; Motoyama, Satoru; Wakita, Akiyuki; Kawakita, Yuta; Li, Jiajia; Nagaki, Yushi; Nanjo, Hiroshi; Terata, Kaori; Imai, Kazuhiro; Saito, Hajime; Minamiya, Yoshihiro

doi:10.1016/j.amjsurg.2018.01.038

Cited by 21 publications

(23 citation statements)

References 34 publications

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“…Prognostic implications of cancerous TLR expression vary. Most typically, TLR expression has been associated with worse prognosis, as in ovarian, lung, colorectal, and tongue carcinomas [13–16], but also association with better prognosis has been evident, as in esophageal carcinoma [17]. Our earlier study showed that strong TLR2 and TLR4 expression predict better prognosis for local PDAC [18].…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 1 predicts favorable prognosis in pancreatic cancer

et al. 2019

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Background The link between inflammation and carcinogenesis is indisputable. In trying to understand key factors at play, cancer research has developed an interest in the toll-like receptors (TLRs), which have shown signs of having prognostic value in various adenocarcinomas. We began investigating the expression of toll-like receptors 1, 3, 5, 7, and 9 to evaluate their prognostic value of patients with pancreatic ductal adenocarcinoma (PDAC). Methods We collected tumor biopsies from 154 stage I-III PDAC patients surgically treated at Helsinki University Hospital between 2002 and 2011, excluding patients undergoing neoadjuvant therapy. We used tissue microarray slides and immunohistochemistry to assess expression of TLRs 1, 3, 5, 7, and 9 in PDAC tissue. Immunopositivity scores and clinicopathological characteristics were subjected to Fisher’s exact test or the linear-by-linear association test. For the survival analysis, we applied the Kaplan-Meier method and log-rank test, and the Cox regression proportional hazard model served for univariate and multivariate analyses. Results Strong TLR1 expression was observable in 60 (39%), strong TLR3 in 48 (31%), strong TLR5 in 58 (38%), strong TLR7 in 14 (9%), and strong TLR9 in 22 (14%) patients. The multivariate analysis showed strong TLR1 expression to associate with better survival than moderate, low, or negative expression (HR = 0.68; 95% CI 0.47–0.99; p = 0.044). Additionally, those few patients with tumors negative for TLR1, TLR3, TLR7, or TLR9 fared poorly (HR = 2.41; 95% CI 1.31–4.43; p = 0.005; n = 13). Conclusion Strong TLR1 expression suggested better prognosis in PDAC patients, whereas negative expression of TLR1, TLR3, TLR7, or TLR9 was a sign of poor prognosis.

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Section: Introductionmentioning

confidence: 99%

Toll-like receptor 1 predicts favorable prognosis in pancreatic cancer

et al. 2019

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“…However, the prognostic values of TLRs were not always consistent between different studies. For instance, Sato et al found that ESCC patients expressing higher levels of TLR-3 had better survival outcomes [ 36 ]. Likewise, higher TLR-4 expression in ESCC patients was associated with better survival compared with weaker expression [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Toll-Like Receptors in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Hasnat

Hujanen

Nwaru

et al. 2020

IJMS

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Head and neck squamous cell carcinoma (HNSCC) is a group of tumours which exhibit low 5 year survival rates. Thus, there is an urgent need to identify biomarkers that may improve the clinical utility of patients with HNSCC. Emerging studies support a role of toll-like receptors (TLRs) in carcinogenesis. Therefore, this systematic review and meta-analysis was performed to assess the prognostic value of TLR immunoexpression in HNSCC patients. We compiled the results of thirteen studies comprising 1825 patients, of which six studies were deemed qualified for quantitative synthesis. The higher immunoexpression of TLR-1 to 5 and 9 was associated with a worsening of the clinical parameters of patients with HNSCC. Furthermore, induced levels of TLR-3, 4, 5, 7 and 9 were found to predict the patients’ survival time. The meta-analysis revealed that TLR-7 overexpression is associated with a decreased mortality risk in HNSCC patients (HR 0.51; 95%CI 0.13–0.89; I2 34.6%), while a higher expression of TLR-5 predicted shorter, but non-significant, survival outcome. In conclusion, this review suggests that TLRs may represent some prognostic value for patients with HNSCC. However, due to small sample sizes and other inherent methodological limitations, more well designed studies across different populations are still needed before TLRs can be recommended as a reliable clinical risk-stratification tool.

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“…Analysis of tissue microarrays. To prepare a validation cohort, primary OSCC tissues were collected from 177 patients who underwent oesophageal resection for OSCC at the Department of Thoracic Surgery, Akita University Hospital between 2000 and 2011 (31). These patients were not administered treatment before curative surgery.…”

Section: Real-time Quantitative Reverse Transcription Pcr (Qrt-pcr) Andmentioning

confidence: 99%

Chromobox 2 Expression Predicts Prognosis After Curative Resection of Oesophageal Squamous Cell Carcinoma

Ueda

Kanda

Sato

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: To investigate the function of chromobox 2 (CBX2) in oesophageal squamous cell carcinoma (OSCC). Materials and Methods: We used real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry to determine CBX2 expression levels in 13 human OSCC cell lines and clinical specimens of two independent cohorts of patients with OSCC. Results: PCR array analysis revealed that CBX2 was co-ordinately expressed with WNT5B in OSCC cell lines. RT-qPCR analysis of clinical samples revealed a high tumour-specific CBX2 expression compared with normal oesophageal tissues. High CBX2 expression was significantly associated with shorter disease-specific survival, hematogenous recurrence, and overall recurrence. Analysis of tissue microarrays of one cohort revealed that patients with higher CBX2 levels tended to have a shorter disease-specific survival. Conclusion: CBX2 overexpression in OSCC tissues may serve as a novel biomarker for predicting survival and hematogenous recurrence. The main histopathological subtypes of oesophageal carcinoma, the sixth leading cause of cancer-related mortality worldwide (1), are adenocarcinoma and oesophageal squamous cell carcinoma (OSCC). The latter is the predominant subtype in Asia and Africa (2). OSCC is generally associated with poor prognosis, mainly because of its high potential to metastasize, which accounts for its dismal overall survival rate of <40%, despite radical treatment (3). A primary goal of efforts to improve the management of OSCC and patients' outcomes is to develop methods that accurately predict the risk of recurrence and survival after curative oesophageal resection (4, 5). Specific biomarkers that predict the recurrence pattern of OSCC, particularly for hematogenous recurrence after radical treatment, will likely contribute to improving patients' outcomes and are therefore the focus of our research. We the aim to identify novel biomarkers, we first focused on the chromobox 2 (CBX2) gene, a member of the chromobox (CBX) gene family, because of its reported association with certain cancers (6-8). CBX2 encodes a subunit of the polycomb group (PcG), whose members form complexes that mediate homeostasis (9). These proteins regulate the expression of numerous genes that control the maintenance, differentiation and proliferation of adult stem cells and cancer cells (10). Biochemical characterization led to the categorization of PcG complexes into two subtypes: Polycomb repressive complex (PRC) 1 and PRC2 (6, 11, 12). The CBX gene family comprises CBX2, CBX4, CBX6, CBX7 and CBX8, which encode components of PRC1 (11). PRC1 members are associated with tumourigenesis. For example, CBX4 plays important roles in cellular proliferation and in the repair of DNA damage in certain human tumours (13, 14). CBX6 was identified as a susceptibility loci by a genome-wide association study on bladder cancer (15). Numerous studies have shown that CBX7 is specifically 391 This article is freely accessible online.

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TLR3 expression status predicts prognosis in patients with advanced thoracic esophageal squamous cell carcinoma after esophagectomy

Cited by 21 publications

References 34 publications

Toll-like receptor 1 predicts favorable prognosis in pancreatic cancer

Toll-like receptor 1 predicts favorable prognosis in pancreatic cancer

The Prognostic Value of Toll-Like Receptors in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Chromobox 2 Expression Predicts Prognosis After Curative Resection of Oesophageal Squamous Cell Carcinoma

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