Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types

Ishiba, Toshiyuki; Hoffmann, Andreas-Claudius; Usher, J.; Elshimali, Yahya; Sturdevant, Todd; Dang, Mai T.; Jaimes, Y.; Tyagi, Rama; Gonzales, Ronald; Grino, Mary; Pinski, Jacek; Barzi, Afsaneh; Raez, Luis E.; Eberhardt, Wilfried; Theegarten, Dirk; Lenz, Heinz‐Josef; Uetake, Hiroyuki; Danenberg, Peter V.; Danenberg, Kathleen D.

doi:10.1016/j.bbrc.2018.04.120

Cited by 47 publications

(34 citation statements)

References 29 publications

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“…The cycling parameters for miRNA were as follows: 95 °C for 30 sec, followed by 40 cycles of 95 °C for 5 sec and 60 °C for 30 sec. Finally, we quantified the miRNA level by using the ΔCt method that was previously described [37][38][39] . In short, the miRNA level = 2^ ΔCt multiplying 1000, where ΔCt was the difference between Ct value of the miRNA of interest to Ct value of internal controls.…”

Section: Samples and Clinical Characteristics This Study Was Conductmentioning

confidence: 99%

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection

Zhao

et al. 2020

Sci Rep

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Recently, we have been seeing emerging applications of non-invasive approaches using serum biomarkers including miRnA and proteins in detection of multiple cancers. currently, majority of these methods only use solitary type of biomarkers, which often lead to non-satisfactory sensitivity and specificity in clinical applications. To this end, we established a unique biomarker panel in this study, which determined both squamous cell carcinoma antigen (SCC Ag) degree and miRNA-29a, miRNA-25, miRNA-486-5p levels in blood for detection of early-stage cervical cancer. We designed our study with two phases: a biomarker discovery phase, followed by an independent validation phase. in total of 140 early-stage cervical cancer patients (i.e., AJCC stage I and II) and 140 healthy controls recruited in the biomarker discovery phase, we achieved sensitivity of 88.6% and specificity of 92.9%. To further assess the predictive power of our panel, we used it to an independent patient cohort that consisted of 60 early-stage cervical cancer individuals as well as 60 healthy controls, and successfully achieved both high sensitivity (80.0%) and high specificity (96.7%). Our study indicated combining analyses of multiple serum biomarkers could improve the accuracy of non-invasive detection of early-stage cervical cancer, and potentially serve as a new liquid biopsy approach for detecting early-stage cervical cancer. For women worldwide in the world, cervical cancer, which is ranked as the fourth most frequently occurred cancer 1 , contributed for 6.6% of the total cases of cancer and 7.5% of the total cancer fatalities of women in 2018 1. Additionally, in women of reproductive age, cervical cancer is the major cause 2-4. The transition to invasive cervical cancer from normal epithelium can take more than a decade 5. In the early stage of Ib and II, the overall survival rate of cervical cancer is 70-90%, but this rate significantly goes down to 15% in the late stage of IVa 6. The main reason of the high death rate of cervical cancer is that its asymptomatic and non-specific nature in the early stages makes early detection extremely difficult 7. If early detection of cervical cancer is achieved, there are various treatment options readily available, which make cervical cancer curable. Currently, Papanicolaou test (Pap smear) and colposcopy are the most common methods for cervical cancer detection. For pap smear screening, it had specificity of 98%, but a sensitivity of 51% 8. Also, Pap smear is not very effective at identifying adenocarcinoma, or cervical carcinoma in situ. For certain early-stage cervical cancer, colposcopy and cervical biopsy may be able to recognize it, but these procedures are invasive for patients, and could delay treatment and generate extra costs and risks 9. Serum tumor biomarkers such as Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC Ag) as well as CA19-9 have been frequently used for detecting and monitoring cervical cancer, because they can be measured non-invasively in blood samples 10-1...

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Section: Samples and Clinical Characteristics This Study Was Conductmentioning

confidence: 99%

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection

Zhao

et al. 2020

Sci Rep

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“…The in vitro and in vivo study in pancreatic tumors shows that the inhibition of the JAK-STAT signaling pathway decreases tumor cell PD-L1 expression and the JAK1/JAK2 inhibitor ruxolitinib can prevent systemic inflammation in the tumor microenvironment and upregulate CTL infiltration and activation to overcome pancreatic cancer resistance to anti-PD-1 immunotherapy 37. Combination of precision medicine and immunotherapy takes individual variability into account in order to design personalized treatment strategies 7. In future, more studies on JAK pathway inhibitors as well as anti-PD1 will be conducted synergistically in NKTL.…”

Section: Discussionmentioning

confidence: 99%

“…Immunotherapy, especially checkpoint inhibitors that block the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1), may provide such alternative therapies 2,3. PD-L1 is expressed by various cancers, including solid tumors and lymphomas, with expression of PD-L1 reportedly being associated with a poorer prognosis 4–7. The interplay between cancer cells and the tumor microenvironment has generated interest in the PD1/PD-L1 pathway as a potential therapeutic target for personalized medicine.…”

Section: Introductionmentioning

confidence: 99%

<p>Anti-PD1 up-regulates PD-L1 expression and inhibits T-cell lymphoma progression: possible involvement of an IFN-γ-associated JAK-STAT pathway</p>

Xue

Zhang

et al. 2019

OTT

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PurposeNK/T-cell neoplasms are rare, highly aggressive, and insensitive to chemotherapy. These lymphomas have a poor prognosis, with patients being vulnerable to relapse. Hence, there is a need for alternative treatments. The purpose of this study is to investigate whether anti-PD1 takes effect on NK/T cell lymphoma.MethodsThe expression of PD-L1 in NK/T cell lines was investigated by flow cytometry and by Western blot. In vivo, overall survival and median survival time of mice bearing an NK/T cell line tumor was assessed. Tumor-infiltrating T cells and monocyte-derived suppressor cells were evaluated by flow cytometry. Levels of PD-L1 and components of the JAK-STAT pathway were assessed in tumor tissues by immunohistochemistry.ResultsNK/T cell lines had greater expression of PD-L1 than normal peripheral blood human NK cells. In vivo, anti-PD1 treatment improved overall survival and median survival time of mice bearing an NK/T cell line. Furthermore, anti-PD1 treatment increased levels of PD-L1. Cultured tumor-infiltrating lymphocytes from mice treated with anti-PD1 had greater levels of IFN-γ than cultured lymphocytes from untreated animals. Further, levels of JAK2 and STAT1 were greater in mice treated with anti-PD1.ConclusionIn vivo, anti-PD1 inhibited the progression of an NK/T-cell lymphoma and up-regulated PD-L1 expression. This up-regulation may be through the IFN-γ-associated JAK-STAT pathway.

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“…PD-L1 expression was detected in the plasma ctRNA of all cancer types at varying frequencies but no PD-L1 messenger RNA (mRNA) was detected in cancer-free individuals there was a high degree of concordance between expression of PD-L1 protein in tumor tissues and PD-L1 gene expression in plasma, and both methods were equally predictive of pharmacological response. These findings may provide additional predictive information on the outcome of patients on anti-PD-L1 therapy [61]. In addition, elevated levels of telomerase reverse transcriptase mRNA (hTERT) are often found in different types of tumors such as breast or colon cancer but no hTERT mRNA was detected in cancer-free individuals [59].…”

Section: Circulating Tumor Messenger Rnamentioning

confidence: 99%

Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer’s Biomarkers

et al. 2020

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In recent years, there has been an increase in knowledge of cancer, accompanied by a technological development that gives rise to medical oncology. An instrument that allows the implementation of individualized therapeutic strategies is the liquid biopsy. Currently, it is the most innovative methodology in medical oncology. Its high potential as a tool for screening and early detection, the possibility of assessing the patient’s condition after diagnosis and relapse, as well as the effectiveness of real-time treatments in different types of cancer. Liquid biopsy is capable of overcoming the limitations of tissue biopsies. The elements that compose the liquid biopsy are circulating tumor cells, circulating tumor nucleic acids, free of cells or contained in exosomes, microvesicle and platelets. Liquid biopsy studies are performed on various biofluids extracted in a non-invasive way, and they can be performed both from the blood and in urine, saliva or cerebrospinal fluid. The development of genotyping techniques, using the elements that make up liquid biopsy, make it possible to detect mutations, intertumoral and intratumoral heterogeneity, and provide molecular information on cancer for application in medical oncology in an individualized way in different types of tumors. Therefore, liquid biopsy has the potential to change the way medical oncology could predict the course of the disease.

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Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types

Cited by 47 publications

References 29 publications

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection

<p>Anti-PD1 up-regulates PD-L1 expression and inhibits T-cell lymphoma progression: possible involvement of an IFN-γ-associated JAK-STAT pathway</p>

Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer’s Biomarkers

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Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types

Cited by 47 publications

References 29 publications

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection

<p>Anti-PD1 up-regulates PD-L1 expression and inhibits T-cell lymphoma progression: possible involvement of an IFN-&gamma;-associated JAK-STAT pathway</p>

Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer’s Biomarkers

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<p>Anti-PD1 up-regulates PD-L1 expression and inhibits T-cell lymphoma progression: possible involvement of an IFN-γ-associated JAK-STAT pathway</p>