scholarly journals Association of Serum Anti-PCSK9 Antibody Levels with Favorable Postoperative Prognosis in Esophageal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Masaaki Ito ◽  
Takaki Hiwasa ◽  
Yoko Oshima ◽  
Satoshi Yajima ◽  
Takashi Suzuki ◽  
...  

BackgroundEsophageal cancer often appears as postoperative metastasis or recurrence after radical surgery. Although we had previously reported that serum programmed cell death ligand 1 (PD-L1) level correlated with the prognosis of esophageal cancer, further novel biomarkers are required for more precise prediction of the prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with the cholesterol metabolism. But there was no report of relationship between serum PCSK9 antibody and cancer. Therefore, we investigated whether anti-PCSK9 antibodies could be a novel biomarker for solid cancer.MethodsSerum levels of anti-PCSK9 antibodies and antigens in patients with solid cancer were analyzed using amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The reactivity of serum antibodies against recombinant PCSK9 protein was investigated by Western blotting, and the expression of PCSK9 antigens in esophageal cancer tissues was examined by immunohistochemical staining.ResultsAlphaLISA showed that serum anti-PCSK9 antibody (s-PCSK9-Ab) levels were significantly higher in patients with esophageal cancer, gastric cancer, colorectal cancer, lung cancer, and breast cancer than in healthy donors, and patients with esophageal cancer had the highest levels. The presence of serum antibody in patients was confirmed by Western blotting. There was no apparent correlation between s-PCSK9-Ab and PCSK9 antigen levels. Immunohistochemical staining demonstrated the expression of PCSK9 antigen in both the cytoplasm and nuclear compartments of esophageal squamous cell carcinoma tissue but not in normal tissue. Compared with patients with low s-PCSK9-Ab levels, those with high s-PCSK9-Ab levels had a favorable postoperative prognosis after radical surgery for esophageal cancer. In the multivariate analysis, tumor depth and s-PCSK9-Ab level were identified as independent prognostic factors. In the univariate analysis of clinicopathological features, high PCSK9 antibody levels were not associated with sex, age, location, tumor depth, lymph node status, squamous cell carcinoma antigen, or p53-Ab, whereas they correlated significantly with PD-L1 levels, which were associated with unfavorable prognosis. Correlation between s-PCSK9-Ab and PD-L1 levels was also confirmed in the logistic regression analysis; therefore, low s-PCSK9-Ab levels could discriminate another poor prognosis group other than high-PD-L1 group.ConclusionsPatients with solid cancer had higher s-PCSK9-Ab levels than healthy donors. High s-PCSK9-Ab levels indicated better prognosis for overall survival after surgery in patients with esophageal cancer.

2006 ◽  
Vol 119 (7) ◽  
pp. 1717-1722 ◽  
Author(s):  
Antonio Rosato ◽  
Michela Pivetta ◽  
Anna Parenti ◽  
Gaetano A. Iaderosa ◽  
Alessia Zoso ◽  
...  

Esophagus ◽  
2021 ◽  
Author(s):  
Eisuke Booka ◽  
Yasuhiro Tsubosa ◽  
Tomoya Yokota ◽  
Shuhei Mayanagi ◽  
Kenjiro Ishii ◽  
...  

Abstract Background Recent comprehensive mutation analyses have revealed a relatively small number of driver mutations in esophageal cancer, implicating a limited number of molecular targets, most of which are also implicated in squamous cell carcinoma. Methods In this study, we investigated genetic alterations in 44 esophageal squamous cell carcinomas (ESCC) and 8 adenocarcinomas (EAC) from Japanese patients as potential molecular targets, based on data from the Japanese version of The Genome Atlas (JCGA). Results Esophageal cancer was characterized by TP53 somatic mutations in ESCC (39/44, 88.6%) and EAC (5/8, 62.5%). In addition to TP53 mutations, somatic mutations in NFE2L2 (16/44, 36.4%), CDKN2A (7/44, 15.9%), and KMT2D (7/44, 15.9%) were more frequently detected in ESCC than in EAC. WRN-truncated type mutations that lead to genomic instability correlate with EAC, but not ESCC. ESCC samples were enriched in ALDH2-associated mutational signature 16 as well as the APOBEC signature. Patients with FAT2 mutations had significantly poorer overall survival compared with those with wild-type status at FAT2 (p < 0.05). Patients with EP300 or PTPRD mutations also had poor progression-free survival compared with respective wild-types (p < 0.05 or p < 0.001). Conclusions These findings may facilitate future precision medicine approaches based on genomic profiling in ESCC and EAC.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 162-162
Author(s):  
Yoshiki Taniguchi ◽  
Koji Tanaka ◽  
Yasuhiro Miyazaki ◽  
Tomoki Makino ◽  
Tsuyoshi Takahashi ◽  
...  

Abstract Background We sometimes experience cases of cervical esophageal cancer which requires laryngectomy due to spread of cancer to larynx. We report a case of esophageal cancer resection with preservation of larynx using intraoperative endoscopic submucosal dissection. Methods The patient was a 59-year-old woman who had dysphagia. She had received total gastrectomy with Roux-en-Y reconstruction for gastric cancer in 2001, chemoradiation (61.2Gy) for esophageal cancer in 2008. Argon plasma coagulation (APC) was performed for the carcinoma in situ of cervical esophagus in 2016. This time superficial 0-IIc tumor was observed at the same site of the scar of APC, and a biopsy revealed squamous cell carcinoma. An endoscopic findings revealed two 0-IIc lesions at distance of 18–22 cm, and 32–34 cm from the incisors, and biopsy resulted in a diagnosis of squamous cell carcinoma. Since tumor was close to the esophageal orifice, the tumor invasion to the larynx was suspected. On the other hand, there were no obvious findings of the submucosal layer invasion, and the both tumor were thought to be limited to the epithelium or lamina propria mucosae (EP/LPM). We performed mediastinoscopic and thoracoscopic transhiatal esophagectomy, subcutaneous ileocolic reconstruction. Results After confirming the tumor invasion to the esophageal orifice by chromoendoscopy with 1% Lugol's iodine solution, we dissected the whole circumference of esophagus in submucosal layer just above the tumor by ESD, put an incision outside of esophageal wall, and resected the esophagus. We preserved short length of muscle layer and performed reconstruction with hypopharynx-ileum anastomosis. Pathological examination revealed squamous cell carcinoma, pT1a-EP, ly0, v0, pPM0, pDM0, pIM0, and curative resection was performed. The postoperative course was uneventful. Conclusion There were no reports of successful larynx-preserving surgery for cervical esophageal cancer using intraoperative ESD. When the tumor was limited in the mucosa, esophagectomy with intraoperative ESD may enable larynx preservation even if the tumor invaded to the esophageal orifice. Disclosure All authors have declared no conflicts of interest.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shirui Chen ◽  
Kai Zhou ◽  
Liguang Yang ◽  
Guohui Ding ◽  
Hong Li

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer.


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