High serum PD‐L1 level is a poor prognostic biomarker in surgically treated esophageal cancer

Ito, Masaaki; Yajima, Satoshi; Suzuki, Takashi; Oshima, Yoshiteru; Nanami, Tatsuki; Sumazaki, Makoto; Shiratori, Fumiaki; Funahashi, Kimihiko; Tochigi, Naobumi; Shimada, Hideaki

doi:10.1002/cam4.2789

Cited by 24 publications

(28 citation statements)

References 31 publications

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“…The results obtained showed that cats presenting mammary carcinoma subtypes associated with more aggressive features and poor prognosis [ 31 ] (HER2-positive and TN normal-like) displayed significantly increased serum PD-1 and PD-L1 levels, as reported in humans with HER2-positive metastatic breast cancer [ 32 ], TN breast cancer [ 23 ], renal cell carcinoma [ 25 ], esophageal cancer [ 33 ], gastric cancer [ 24 ], advanced pancreatic cancer [ 34 ], lung cancer [ 35 ] and metastatic melanoma [ 36 ] correlated to shorter overall survival and tumor-free survival times [ 23 , 25 , 32 , 33 , 35 ], suggesting a conserved role of the PD-1/PD-L1 axis in both species. Moreover, as reported in humans, our findings uncovered a positive correlation between serum PD-1 and PD-L1 levels, suggesting that both molecules are co-regulated [ 23 , 34 ].…”

Section: Discussionmentioning

confidence: 97%

Serum PD-1/PD-L1 Levels, Tumor Expression and PD-L1 Somatic Mutations in HER2-Positive and Triple Negative Normal-Like Feline Mammary Carcinoma Subtypes

Nascimento

Urbano

Gameiro

et al. 2020

Cancers

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Tumor microenvironment has gained great relevance due to its ability to regulate distinct checkpoints mediators, orchestrating tumor progression. Serum programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) levels were compared with healthy controls and with serum cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and tumor necrosis factor-alpha (TNF-α) levels in order to understand the role of PD-1/PD-L1 axis in cats with mammary carcinoma. PD-1 and PD-L1 expression was evaluated in tumor-infiltrating lymphocytes (TILs) and cancer cells, as the presence of somatic mutations. Results showed that serum PD-1 and PD-L1 levels were significantly higher in cats with HER2-positive (p = 0.017; p = 0.032) and triple negative (TN) normal-like mammary carcinomas (p = 0.004; p = 0.015), showing a strong positive correlation between serum CTLA-4 and TNF-α levels. In tumors, PD-L1 expression in cancer cells was significantly higher in HER2-positive samples than in TN normal-like tumors (p = 0.010), as the percentage of PD-L1-positive TILs (p = 0.037). PD-L1 gene sequencing identified two heterozygous mutations in exon 4 (A245T; V252M) and one in exon 5 (T267S). In summary, results support the use of spontaneous feline mammary carcinoma as a model for human breast cancer and suggest that the development of monoclonal antibodies may be a therapeutic strategy.

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Section: Discussionmentioning

confidence: 97%

Serum PD-1/PD-L1 Levels, Tumor Expression and PD-L1 Somatic Mutations in HER2-Positive and Triple Negative Normal-Like Feline Mammary Carcinoma Subtypes

Nascimento

Urbano

Gameiro

et al. 2020

Cancers

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“…Some studies have reported that patients with a higher expression of PD-L1 in cancer cells are correlated with preferential outcome in lung cancer (13). However, others have found that a high PD-L1 expression level is a poor prognostic factor in esophageal and cervical cancers (14,15). Although recent studies have been carried out (16)(17)(18), the association between the clinical response to anti-PD-1 antibodies and PD-L1 expression in HCC tumor cells remains unclear.…”

Section: Original Articlementioning

confidence: 99%

The landscape of PD-L1 expression and somatic mutations in hepatocellular carcinoma

Liang

Liu

et al. 2021

J Gastrointest Oncol

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Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and becoming the third-leading cause of cancer-related mortality worldwide. Despite the immune checkpoint inhibitors and molecular targeted therapies have shown preferable efficacy in HCC, large number of HCC patients do not respond effectively to anti-PD-1 reagents. Besides, the accumulation of genetic mutations in cancer cells may lead to the therapy resistant. Hence, there are clinical gaps between genetic and transcriptomic biomarkers for the HCC treatment. Methods: To investigate the genetic mapping of liver cancer, targeted deep sequencing (TDS) and bioinformatics analysis were performed on hepatocellular carcinoma (HCC) tumor tissues and matched blood samples. Furthermore, copy number variants (CNVs) and Tumor mutation burden (TMB) were calculated. Immunohistochemistry was applied to determine the PD-L1 expression in HCC tumor tissues. Clinical characteristic, PD-L1 expression, and the TMB were analyzed in 32 HCC patients.Results: This study indicated that the PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group, and PD-L1 positive patients were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients. We also verified the top 30 mutated genes, including TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1, in our dataset. Our results indicated that PD-L1 positive patients possessed more tumors with vascular invasion and advanced CCLC stage. Moreover, PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group.Conclusions: These findings could improve our understanding of the effects of immune checkpoint therapies on prognosis, and could facilitate the monitoring of somatic mutations in HCC.

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“…Regarding biomarker, we recently reported about PD-L1, which is a poor prognostic biomarker in esophageal cancer ( 4 ). Unexpectedly, in the present study, PD-L1 correlated positively with favorable-prognosis-associated s-PCSK9-Ab levels ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Each clinicopathological feature and prognosis of these patients was examined. The cutoff level of serum PD-L1 was set at 75 percentile (65.6 pg/mL) of esophageal cancer ( 4 ).…”

Section: Methodsmentioning

confidence: 99%

“…Nivolumab has been recently used for treating esophageal cancer worldwide; however, the treatment results have not been necessarily satisfactory ( 3 ). Regarding newly developed biomarkers, we had previously reported that high serum levels of programmed cell death ligand 1 (PD-L1) exhibited poor prognosis in patients with esophageal cancer ( 4 ). PD-L1 could become a predictive marker of prognosis, and it is expected to be used in the early diagnosis and treatment of immune checkpoint inhibitors for improving curability.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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High serum PD‐L1 level is a poor prognostic biomarker in surgically treated esophageal cancer

Cited by 24 publications

References 31 publications

Serum PD-1/PD-L1 Levels, Tumor Expression and PD-L1 Somatic Mutations in HER2-Positive and Triple Negative Normal-Like Feline Mammary Carcinoma Subtypes

Serum PD-1/PD-L1 Levels, Tumor Expression and PD-L1 Somatic Mutations in HER2-Positive and Triple Negative Normal-Like Feline Mammary Carcinoma Subtypes

The landscape of PD-L1 expression and somatic mutations in hepatocellular carcinoma

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

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