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High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.

ABSTRACT: PURPOSE:The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. Programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 may be used as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of patients with CA and their response to immune checkpoint inhibition therapy. METHODS:In the present study, the clinical stage for all 82 patients with cervical adenocarcinoma was classified according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO); there were 5, 48, 5, 14, 8, and 2 patients with stage IA, IB, IIA, IIB, IIIB, and IVB disease, respectively. The levels of PD-1, PD-L1, and CD8 were analyzed by the immunohistochemical analysis of the formalin-fixed paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed using the Kaplan-Meier method and univariate and multivariate Cox proportional hazard regression models. RESULTS:We observed a significant inverse correlation between the expression of PD-1 and CD8 (p?=?0.001, chi-square test). We also found a significant inverse correlation between the expression of PD-L1 and CD8 (p?=?0.027). The overall survival and progression-free survival rates were significantly worse in patients with positive PD-1 expression (p?=?0.031; p?=?0.087, respectively). CONCLUSION:Our results suggest that a high PD-1 expression is associated with a poor prognosis in patients with CA. Further research is necessary to identify the molecular mechanisms that mediate this association.

SUBMITTER: Ishikawa M

PROVIDER: S-EPMC7266794 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.

Ishikawa Masako M Nakayama Kentaro K Nakamura Kohei K Yamashita Hitomi H Ishibashi Tomoka T Minamoto Toshiko T Iida Kouji K Razia Sultana S Ishikawa Noriyoshi N Nakayama Satoru S Otsuki Yoshiro Y Kyo Satoru S

Archives of gynecology and obstetrics 20200520 1

<h4>Purpose</h4>The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. Programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 may be used as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of patients with CA and their response to immune checkpoint inhibition therapy.<h4>Methods</h4>In the prese ...[more]

PMID: 32435885

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Project description:Aims: Colon adenocarcinoma (COAD) is responsible for 90% of all colorectal cancer cases and is one of the most common causes of cancer-related deaths worldwide. ATP6V1s (cytosolic V1 domain of vacuolar adenosine triphosphatase) participate in the biological process of transporting hydrogen ions and are implicated in tumor growth and metastasis. ATP6V1C2 as a family member has been documented to associate with esophageal carcinoma and renal clear cell carcinoma, while its roles in COAD remain elusive. Methods: The expression status, potential molecular mechanism, and prognostic value of ATP6V1C2 in COAD were investigated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, its biological roles in COAD were explored through in vitro studies. Results: ATP6V1C2 showed a significantly higher expression level in COAD compared with matched non-cancerous tissues. High expression of ATP6V1C2 predicted a shorter overall survival both in TCGA and GEO COAD datasets, and ATP6V1C2 was identified as an independent factor associated with overall survival in COAD. Bioinformatic analyses showed that high expression of ATP6V1C2 was associated with high epithelial-mesenchymal transition (EMT) score and Wnt signaling pathway was significantly enriched from differentially expressed genes between ATP6V1C2-high and -low group. We also found that high expression of ATP6V1C2 could decrease pathway activity of CD8 T effector implicated in tumor microenvironment (TME). In vitro study revealed that ATP6V1C2 knockdown resulted in aberrant expression of Wnt- and EMT-related genes and inhibited COAD cell proliferation and growth. Conclusion: This is the first study to reveal the molecular functions of ATP6V1C2 in COAD. Our study suggests that overexpressed ATP6V1C2 might promote EMT by activating Wnt signaling pathway, resulting in cancer metastasis and poor prognosis. This study paves the way for understanding potential molecular mechanisms and therapeutic perspectives in COAD.

Dataset Information

High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.

Publications

High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.

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