Impact of gene expression of orotate phosphoribosyl transferase for complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4566-4566
Author(s):  
T. Kajiwara ◽  
T. Nishina ◽  
I. Hyodo ◽  
T. Moriwaki ◽  
S. Endo ◽  
...  

4566 Background: Chemoradiotherapy (CRT) is a potential alternative to surgery in patients with squamous cell carcinoma of the esophagus. Complete response (CR) to CRT is essential for a good prognosis and there is a need for a predictive method of CR in CRT. Methods: The pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 41 patients treated with a definitive concurrent CRT (5-FU/CDDP and 60 Gy) for esophageal cancer (cStage II or III). cDNA was derived from tumor cells of biopsy specimens by the laser capture microdissection and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using fluorescence-based, real-time reverse transcription PCR. Gene expression levels of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase (OPRT), metylenetetrahydrofolate reductase, dihydrofolate reductase (DHFR), excision repair cross-complementing gene 1, vascular endothelial growth factor, epidermal growth factor receptor and matrix metalloproteinase 9 (MMP-9) were measured. Results: Median gene expression levels of OPRT and DHFR were significantly higher in CR patients (p=0.0206 and 0.0191, respectively). MMP-9 was significantly lower in CR patients (p=0.0436). When the median values of the gene expression levels were selected as the cutoff values, CR rate was significantly higher in the high OPRT group and high DHFR group (p=0.0104 and 0.0104, respectively). However, there was no statistical difference in CR rate between the low MMP-9 group and the high MMP-9 group. Multivariate analysis, including clinical stage and biomarkers, revealed that high OPRT gene expression was an independent predictive factor of CR (p=0.0329, relative risk=6.65, 95% confidence interval, 1.17–37.89%). Conclusions: The measurement of OPRT gene expression in tumor biopsies may be a predictive factor of CR to CRT in patients with squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.

2009 ◽  
Vol 124 (12) ◽  
pp. 2911-2916 ◽  
Author(s):  
Chizuru Hirano ◽  
Masaki Nagata ◽  
Arhab A. Noman ◽  
Nobutaka Kitamura ◽  
Makoto Ohnishi ◽  
...  

Cancer ◽  
2008 ◽  
Vol 112 (6) ◽  
pp. 1272-1281 ◽  
Author(s):  
Akira Kurokawa ◽  
Masaki Nagata ◽  
Nobutaka Kitamura ◽  
Arhab A. Noman ◽  
Makoto Ohnishi ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuangui Chen ◽  
Rui Feng ◽  
Bailin He ◽  
Jun Wang ◽  
Na Xian ◽  
...  

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed. Programmed Death-1 Homolog (PD-1H) is a negative checkpoint regulator that inhibits antitumor immune responses. Here, PD-1H expression in 114 patients with ESCC was evaluated by immunohistochemistry. Next, 12 randomly selected tumor tissue sections were used to assess the colocalization of PD-1H protein and multiple immune markers by multiplex immunohistochemistry. Our results demonstrated that PD-1H was expressed at high frequency in ESCC tumor tissues (85.1%). PD-1H protein was predominantly expressed in CD68+ tumor-associated macrophages and expressed at low levels in CD4+ T cells and CD8+ T cells in ESCC tumor tissues. Furthermore, based on ESCC data in The Cancer Genome Atlas (TCGA), the gene expression levels of PD-1H were positively associated with the infiltration levels of immune-activated cells especially CD8+ cytotoxic T cells. In contrast, the gene expression levels of PD-1H were negatively correlated with myeloid-derived suppressor cells (MDSCs). Importantly, PD-1H expression in tumor sites was significantly correlated with favorable overall survival in patients with ESCC. Collectively, our findings first provided direct information on the PD-1H expression pattern and distribution in ESCC, and positive correlation of PD-1H expression with overall survival suggested PD-1H expression levels could be a significant prognostic indicator for patients with ESCC. Future studies need to explore the immunoregulatory of PD-1H in the tumor microenvironment of ESCC.


Oncology ◽  
2009 ◽  
Vol 76 (5) ◽  
pp. 342-349 ◽  
Author(s):  
Takeshi Kajiwara ◽  
Tomohiro Nishina ◽  
Ichinosuke Hyodo ◽  
Toshikazu Moriwaki ◽  
Shinji Endo ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4043
Author(s):  
Pei-Feng Liu ◽  
Chih-Wen Shu ◽  
Cheng-Hsin Lee ◽  
Huei-Cin Sie ◽  
Huei-Han Liou ◽  
...  

Guanylate binding protein 5 (GBP5) is the interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) and is involved in pathogen defense. However, the role played by GBP5 in cancer development, especially in oral squamous cell carcinoma (OSCC), is still unknown. Herein, next-generation sequencing analysis showed that the gene expression levels of GBP5 were significantly higher in OSCC tissues compared with those found in corresponding tumor adjacent normal tissues (CTAN) from two pairs of OSCC patients. Higher gene expression levels of GBP5 were also found in tumor tissues of 23 buccal mucosal squamous cell carcinoma (BMSCC)/14 tongue squamous cell carcinoma (TSCC) patients and 30 oral cancer patients from The Cancer Genome Atlas (TCGA) database compared with those in CTAN tissues. Immunohistochemical results showed that protein expression levels of GBP5 were also higher in the tumor tissues of 353 OSCC patients including 117 BMSCC, 187 TSCC, and 49 lip squamous cell carcinoma patients. Moreover, TCGA database analysis indicated that high gene expression levels of GBP5 were associated with poor overall survival in oral cancer patients with moderate/poor cell differentiation, and associated with poor disease-free survival in oral cancer patients with moderate/poor cell differentiation and lymph node metastasis. Furthermore, GBP5-knockdowned cells exhibited decreased cell growth, arrest at G1 phase, and decreased invasion/migration. The gene expression of markers for epithelial−mesenchymal transition and cancer stemness was also reduced in GBP5-silenced oral cancer cells. Taken together, GBP5 might be a potential biomarker and therapeutic target for OSCC patients, especially for those with poor cell differentiation and lymph node metastasis.


PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Meng Lian ◽  
Jiaming Chen ◽  
Xixi Shen ◽  
Lizhen Hou ◽  
Jugao Fang

The upregulation of peroxisome proliferator-activated receptor gamma (PPARG) has been shown to increase the chemosensitivity of several human cancers. This study is aimed at studying if PPARG sensitizes hypopharyngeal squamous cell carcinoma (HSCC) in chemotherapeutic treatments and at dissecting possible mechanisms of observed effects. We integrated large-scale literature data and HSCC gene expression data to identify regulatory pathways that link PPARG and chemosensitivity in HSCC. Expression levels of molecules within the PPARG regulatory pathways were compared in 21 patients that underwent chemotherapy for primary HSCC, including 12 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP). In the CPS group, expression levels of PPARG were higher than that in the CNSP group (log‐fold‐change=0.50). Structured text mining identified two chemosensitivity-related regulatory pathways driven by PPARG. In the CSP group, expression levels for 7 chemosensitivity-promoting genes were increased, while for 13 chemosensitivity suppressing the gene expression levels were decreased. Our results support the chemosensitivity-promoting role of PPARG in HSCC tumor cells, most likely by affecting both cell proliferation and cell motility pathways.


Sign in / Sign up

Export Citation Format

Share Document