The Prognostic Value of Programmed Death-Ligand 1 in a Chinese Cohort With Clear Cell Renal Cell Carcinoma

Xiao, Wenjun; Xu, Fujiang; Zhang, Xuan; Zhou, Shuxian; Zhang, Hai-Liang; Dai, Bo; Zhu, Yao; Shi, Guohai; Shen, Yijun; Zhu, Yiping; Qu, Yuanyuan; Zhao, Jian; Ye, Dingwei

doi:10.3389/fonc.2019.00879

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…Some studies could support our findings, for instance, Xiao and colleagues assessed the expression levels of mRNA and protein of PD-L1 in 330 patients with non-metastatic clear cell renal cell carcinoma via qRT-PCR and IHC test, respectively, and 292 patients had consistent results for mRNA and the PD-L1 protein ( 26 ), indicating that the evaluation of PD-L1 expression based on qRT-PCR technology is predictive valuable. Another study showed that, depending on the 28-8 antibody employed, the agreement between PD-L1 mRNA and IHC staining in primary non-small cell lung cancer tissues was excellent, and the differences became apparent in metastatic lesions ( 27 ).…”

Section: Discussionsupporting

confidence: 70%

Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy

Qiu

Chen

et al. 2022

Front. Oncol.

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BackgroundProgrammed death ligand 1 (PD-L1) immunohistochemistry (IHC) has been proposed as a predictive biomarker to predict response to immunotherapy. Given the limitations of IHC test in PD-L1 detection, this study aimed to investigate the technical feasibility of using quantitative RT-PCR (qRT-PCR) to replace IHC in PD-L1 detection in gastrointestinal tumors.Materials and methodsThe Cancer Genome Atlas database was used to evaluate the relationship between PD-L1 expression in tumor tissue and the patient prognosis. In addition, 52 patients with gastrointestinal cancer were enrolled and divided into the stomach (STAD), colon (COAD), and rectum (READ) adenocarcinoma cohorts. IHC test was used to determine the PD-L1 level of the tissue specimens, and the qRT-PCR test was used to analyze the mRNA expression in both blood and tissue specimens. Moreover, the correlation between blood PD-L1 mRNA expression and immunotherapy efficacy was investigated in additional 15 patients with gastric cancer that further enrolled.ResultsThe expression level of PD-L1 in tumor tissue is related to the tumor stage of COAD (p-value = 0.001) and primary therapy outcomes in patients with READ (p-value = 0.003) but not significantly correlated to the overall survival (OS) time of patients with gastrointestinal cancer. Moreover, the concordance of PD-L1 mRNA expression level of tissue and paired blood samples is low, despite a weak linear relationship that was found in the STAD cohort (r = 0.43, p-value = 0.049). We further demonstrated that qRT-PCR results in both tissue and blood specimens were numerically but not statistically significant consistent with IHC results (corresponding to a p-value of 0.84 and 0.55, respectively). Remarkably, high PD-L1 expression in blood of patients with STAD shows a better response to immunotherapy (p-value = 0.04), which could be well identified at the relative expression cutoff of 1.5 (sensitivity of 85.7%, specificity of 75.0%, and AUC of 0.82).ConclusionsOur study established a novel strategy for rapidly distinguishing patients with gastrointestinal cancer with the response to immunotherapy and has potential clinical benefits.

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Section: Discussionsupporting

confidence: 70%

Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy

Qiu

Chen

et al. 2022

Front. Oncol.

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“…Clear cell RCC is the most common RCC subtype and has already been extensively analyzed for PD-L1 expression in earlier studies [ 14 , 18 – 21 , 25 , 26 , 28 , 29 , 31 , 32 , 35 , 39 , 40 , 49 , 51 ]. Our rate of 2–6% PD-L1 positive clear cell RCCs (depending on the cut-off level to define PD-L1 positivity) is in the lower range of published data with PD-L1 positivity ranging from 0 to 77% in studies analyzing 34–756 clear cell RCCs [ 14 , 18 – 21 , 25 , 26 , 28 , 29 , 31 , 32 , 35 , 39 , 40 , 49 , 51 ]. Reasons that are typically hold accountable for discrepant results in IHC studies include different antibodies, staining protocols, and criteria to define positivity.…”

Section: Discussionmentioning

confidence: 99%

Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer

et al. 2021

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Background PD-L1 expression predicts response to immune checkpoint inhibitors in renal cell carcinomas (RCC), but has also been suggested to be linked to poor patient outcome. Methods We analyzed PD-L1 in > 1400 RCC in a tissue microarray format by immunohistochemistry. Results were compared with histological tumor type, parameters of cancer aggressiveness, and intratumoral CD8+ cytotoxic cells. Result At a cut-off level of 5% PD-L1 positive tumor cells, PD-L1 positivity was seen in 6.3% of 633 clear cell RCC (ccRCC), 18.2% of 165 papillary RCC, 18.8% of 64 chromophobe RCC, and 41.7% of 103 oncocytomas. In ccRCC, PD-L1 positivity was significantly linked to high ISUP (p < 0.0001), Fuhrman (p < 0.0001), Thoenes grade (p < 0.0001), distant metastasis (p = 0.0042), short recurrence-free (p < 0.0001), and overall survival (p = 0.0002). Intratumoral CD8+ lymphocytes were more frequent in PD-L1 positive (1055 ± 109) than in PD-L1 negative ccRCC (407 ± 28; p < 0.0001). PD-L positive immune cells were seen in 8.2% of all RCC and 13.9% of papillary RCC. In ccRCC, PD-L1 positive immune cells were linked to high numbers of tumor-infiltrating CD8+ cells (p < 0.0001), high ISUP (p < 0.0001), Fuhrman (p = 0.0027), and Thoenes grade (p < 0.0001), and poor tumor-specific survival (p = 0.0280). Conclusions These data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.

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“…The H-score was determined by the following calculation method: H-score = % of weakly stained cells (1+) + 2 × % of moderately stained cells (2+) + 3 × % of strongly stained cells (3+). Positive CD47 expression was defined as H-score ≥ 5 (≥5% tumor cell membrane staining) according to reference studies [ 26 , 27 ]. All immunohistochemical assessments were blinded to the clinicopathological parameters and patient survival.…”

Section: Methodsmentioning

confidence: 99%

CD47 Expression Predicts Unfavorable Prognosis in Clear Cell Renal Cell Carcinoma after Curative Resection

et al. 2022

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The role of CD47 expression as a ‘do not eat me’ signal that inhibits phagocytosis of tumor cells by macrophages is well established. Immune checkpoint therapy that targets CD47 has been successful in preclinical trials and is currently undergoing clinical investigation for various human malignancies. Here, the clinicopathological correlation with CD47 expression in clear cell renal cell carcinoma (ccRCC) was explored. CD47 expression was evaluated by immunohistochemical staining in tissue microarray sections of 235 ccRCC tissues. CD47 expression was observed in 28 (11.9%) of 235 ccRCC tissues and was significantly associated with higher WHO/ISUP grade (p = 0.001), frequent lymphovascular invasion (p = 0.036), frequent renal vein thrombus (p = 0.018), frequent sinus fat invasion (p = 0.004), frequent sarcomatous change (p = 0.001), higher pT stage (p = 0.002), higher pN stage (p = 0.002), higher pM stage (p < 0.001), and advanced American Joint Committee on Cancer stage (p = 0.002). In the survival analyses, positive CD47 expression was associated with cancer-specific survival (p = 0.003). However, positive CD47 expression was not associated with recurrence-free survival. In conclusion, CD47 expression was associated with adverse clinicopathological parameters and cancer-specific survival in patients with ccRCC.

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The Prognostic Value of Programmed Death-Ligand 1 in a Chinese Cohort With Clear Cell Renal Cell Carcinoma

Cited by 7 publications

References 28 publications

Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy

Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy

Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer

CD47 Expression Predicts Unfavorable Prognosis in Clear Cell Renal Cell Carcinoma after Curative Resection

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