- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05214885
Novel Biomarkers of Hypoxia and Metabolism in Clear Cell Renal Cell Carcinoma
Renal cell carcinoma (RCC) is one of the common malignant tumors in human beings and originates from the renal tubular epithelium. Clear cell renal cell carcinoma (ccRCC) is the main pathological type of RCC. Due to the lack of reliable biomarkers and clinical symptoms for early diagnosis, imaging findings such as ultrasound and CT are needed. When the patients presented typical symptoms, for example, hematuria, backache, and abdominal mass, some of them are in advanced stages of cancer. About a quarter of patients had metastasis at the first diagnosis, and the 5-year survival rate of these patients was less than 10%. Therefore, the early diagnosis of ccRCC and the prevention of tumor recurrence and metastasis are of great significance.
The preliminary studies suggested that some hypoxia and metabolism-related molecules were highly expressed in ccRCC tumors but low in normal kidney tissues. The molecules included carbonic anhydrase IX/9 (CA IX/CA9), the mitochondrial NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2(NDUFA4L2), angiopoietin-like protein 4(ANGPTL4), hypoxia inducible lipid droplet-associated (HILPDA), and egl-9 family hypoxia-inducible factor 3( EGLN3) et al . Cell-free DNA methylomes were also highly expressed in the blood of ccRCC patients.
In order to further verify the expression status of the above novel biomarkers in ccRCC, the investigators will detect the expressions of these molecules in the tumor and adjacent tissues from 140 ccRCC patients by RT-PCR, Western blot, and immunohistochemistry.140 healthy people were selected as the control group. 30 patients with benign kidney diseases were selected as another control group. Blood and urine samples from the ccRCC group and the control group were collected. The mRNA and protein levels of the above molecules in blood or urine samples were detected by qRT-PCR and ELISA. The correlation between the expression of the above new biomarkers and clinical data, such as early diagnosis, pathological grade, recurrence and metastasis, and survival time, was statistically analyzed. The above molecular changes were dynamically detected before surgery, 1 week, and 6 months after surgery. A receiver-operating characteristic curve (ROC) was used to determine the threshold value of these biomarkers for the diagnosis of renal clear cell carcinoma.
The study is to explore the specific tumor biomarker spectrum for clinical diagnosis, evaluation of recurrence, metastasis, and prognosis of ccRCC, which will be auxiliary early screening and diagnosis, reducing the harm of renal cancer to human health.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Li Zhang, Dr.
- Phone Number: +86-531-89269680
- Email: maggie_zhangli@139.com
Study Locations
-
-
-
Jinan, China
- Recruiting
- The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital
-
Contact:
- li zhang, Ph.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
The patient was preliminarily diagnosed as renal carcinoma by imaging examination and finally diagnosed as clear cell renal cell carcinoma by pathology. The patient was treated normally and no intervention was required in this study.
There is no need to collect additional samples. A small part of the remaining samples from routine biochemical and pathological tests of patients can be enough to complete the detections required by the study.
Description
Inclusion Criteria:
- The age and sex of the healthy control group were matched with that of ccRCC patient group. There was no tumor in the kidney or other parts of the body, and no tumor in the blood system. The healthy control group did not have any renal benign diseases, such as kidney stones, diabetic nephropathy, inflammation, and uremia. There are no inflammatory diseases in other parts of the body; the functions of the liver, kidney, and heart were normal.
Exclusion Criteria:
- The volunteer has tumors in the kidney or other parts of the body, or blood system tumors; The volunteer has benign kidney diseases, such as kidney stones, diabetic nephropathy, nephritis and uremia, etc; The patient has inflammatory disease elsewhere. If the volunteer has any one of the above diseases, it shall be excluded.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
the ccRCC patient group
The age and gender of patients are not limited.
The patient was preliminarily diagnosed as renal carcinoma by imaging examination and finally diagnosed as clear cell renal cell carcinoma by pathology.
|
The patient was treated normally and no intervention was required in this study
|
the healthy control group
The age and sex of the healthy control group were matched with that of ccRCC patient group.
There was no tumor in the kidney or other parts of the body, and no tumor in the blood system.
The healthy control group did not have any renal benign diseases, such as kidney stones, diabetic nephropathy, inflammation, and uremia.
There are no inflammatory diseases in other parts of the body.
The functions of the liver, kidney, and heart were normal.
|
The patient was treated normally and no intervention was required in this study
|
the benign kidney disease group
The age and sex of this group were matched with that of ccRCC patient group.
The patient did not have any tumor but had one of the benign kidney diseases, such as kidney stones, diabetic nephropathy, inflammation, and uremia.
The functions of the liver and heart were normal.
|
The patient was treated normally and no intervention was required in this study
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Detection of novel biomarkers in ccRCC patients before surgery
Time Frame: For ccRCC patients, these six novel biomarkers were detected 1 to 3 days before surgery
|
|
For ccRCC patients, these six novel biomarkers were detected 1 to 3 days before surgery
|
Detection of novel biomarkers in ccRCC patients 1 week after surgery
Time Frame: For ccRCC patients, the detection of these biomarkers were completed within one week after surgery
|
|
For ccRCC patients, the detection of these biomarkers were completed within one week after surgery
|
Detection of novel biomarkers in ccRCC patients at 6 months after surgery
Time Frame: For ccRCC patients, these six novel biomarkers were detected at 6 months postoperatively
|
|
For ccRCC patients, these six novel biomarkers were detected at 6 months postoperatively
|
Detection of novel biomarkers in the control groups as baseline
Time Frame: For the healthy control group and the benign kidney disease group, the levels of these six biomarkers were detected as baseline.
|
|
For the healthy control group and the benign kidney disease group, the levels of these six biomarkers were detected as baseline.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Li Zhang, Dr., The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital
Publications and helpful links
General Publications
- Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol. 2016 Jul;70(1):93-105. doi: 10.1016/j.eururo.2016.02.029. Epub 2016 Feb 28.
- Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009 Mar 28;373(9669):1119-32. doi: 10.1016/S0140-6736(09)60229-4. Epub 2009 Mar 5.
- Lucarini L, Magnelli L, Schiavone N, Crisci A, Innocenti A, Puccetti L, Cianchi F, Peri S, Supuran CT, Papucci L, Masini E. Plasmatic carbonic anhydrase IX as a diagnostic marker for clear cell renal cell carcinoma. J Enzyme Inhib Med Chem. 2018 Dec;33(1):234-240. doi: 10.1080/14756366.2017.1411350.
- Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordonez A, Corral-Escariz M, Soro I, Lopez-Bernardo E, Perales-Clemente E, Martinez-Ruiz A, Enriquez JA, Aragones J, Cadenas S, Landazuri MO. Induction of the mitochondrial NDUFA4L2 protein by HIF-1alpha decreases oxygen consumption by inhibiting Complex I activity. Cell Metab. 2011 Dec 7;14(6):768-79. doi: 10.1016/j.cmet.2011.10.008. Epub 2011 Nov 17.
- Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006 Mar;3(3):187-97. doi: 10.1016/j.cmet.2006.01.012.
- Liu L, Lan G, Peng L, Xie X, Peng F, Yu S, Wang Y, Tang X. NDUFA4L2 expression predicts poor prognosis in clear cell renal cell carcinoma patients. Ren Fail. 2016 Sep;38(8):1199-205. doi: 10.1080/0886022X.2016.1208517. Epub 2016 Jul 25.
- Miikkulainen P, Hogel H, Seyednasrollah F, Rantanen K, Elo LL, Jaakkola PM. Hypoxia-inducible factor (HIF)-prolyl hydroxylase 3 (PHD3) maintains high HIF2A mRNA levels in clear cell renal cell carcinoma. J Biol Chem. 2019 Mar 8;294(10):3760-3771. doi: 10.1074/jbc.RA118.004902. Epub 2019 Jan 7.
- Povero D, Johnson SM, Liu J. Hypoxia, hypoxia-inducible gene 2 (HIG2)/HILPDA, and intracellular lipolysis in cancer. Cancer Lett. 2020 Nov 28;493:71-79. doi: 10.1016/j.canlet.2020.06.013. Epub 2020 Aug 18.
- Galaup A, Cazes A, Le Jan S, Philippe J, Connault E, Le Coz E, Mekid H, Mir LM, Opolon P, Corvol P, Monnot C, Germain S. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18721-6. doi: 10.1073/pnas.0609025103. Epub 2006 Nov 27.
- Nuzzo PV, Berchuck JE, Korthauer K, Spisak S, Nassar AH, Abou Alaiwi S, Chakravarthy A, Shen SY, Bakouny Z, Boccardo F, Steinharter J, Bouchard G, Curran CR, Pan W, Baca SC, Seo JH, Lee GM, Michaelson MD, Chang SL, Waikar SS, Sonpavde G, Irizarry RA, Pomerantz M, De Carvalho DD, Choueiri TK, Freedman ML. Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nat Med. 2020 Jul;26(7):1041-1043. doi: 10.1038/s41591-020-0933-1. Epub 2020 Jun 22. Erratum In: Nat Med. 2020 Sep 7;:
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CT2021-11-23
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Clear Cell Renal Cell Carcinoma
-
Celldex TherapeuticsTerminatedKidney Neoplasms | Metastatic Renal Cell Carcinoma | Ovarian Clear Cell Carcinoma | Papillary Renal Cell Carcinoma | Renal Cell Carcinoma (RCC) | Clear-cell Renal Cell CarcinomaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Renal Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Advanced Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v8 | Stage IV Renal Cell Cancer AJCC v8 | Metastatic Sarcomatoid Renal Cell Carcinoma | Advanced Renal Cell Carcinoma | Unresectable Renal Cell... and other conditionsUnited States
-
Guru SonpavdePfizer; Hoosier Cancer Research NetworkWithdrawnKidney Cancer | Clear-cell Renal Cell Carcinoma | RCC | Clear-cell Kidney CarcinomaUnited States
-
Peloton Therapeutics, Inc.Active, not recruitingA Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)Kidney Cancer | Clear Cell Renal Cell Carcinoma | Glioblastoma | Solid Tumor | Glioblastoma Multiforme | Advanced Solid Tumors | GBM | Solid Tumor, Adult | Solid Carcinoma | Glioblastoma, Adult | ccRCC | RCC, Clear Cell Adenocarcinoma | RCC | Renal Cell Carcinoma, Metastatic | Renal Cell Carcinoma Recurrent | Renal Cell...
-
Queen Mary University of LondonAstraZeneca; Vall d'Hebron Institute of OncologyActive, not recruitingRenal Clear Cell Carcinoma | Renal Papillary Cell CarcinomaUnited Kingdom
-
AmgenCompletedRenal Cell Carcinoma | Clear Cell Renal Cell Carcinoma | Clear Cell Renal Carcinoma | Renal Cell AdenocarcinomaFrance, United States, Germany
-
Association Pour La Recherche des Thérapeutiques...CompletedClear-cell Metastatic Renal Cell Carcinoma | Clear-cell Renal CarcinomaFrance
-
University of WashingtonMerck Sharp & Dohme LLC; Prometheus LaboratoriesTerminatedMetastatic Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer | Advanced Clear Cell Renal Cell Carcinoma | Stage IV Renal Cell CancerUnited States
-
Telix International Pty LtdGrand Pharmaceutical (China) Co., Ltd.CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Cancer | Suspected Recurrent Renal Clear Cell CarcinomaChina
-
Mabwell (Shanghai) Bioscience Co., Ltd.Not yet recruitingAdvanced Clear Cell Renal Cell Carcinoma
Clinical Trials on No intervention was required for patients or control group in this study
-
Qianfoshan HospitalNot yet recruiting
-
VA Puget Sound Health Care SystemCompletedChronic Obstructive Pulmonary Disease
-
Kerman University of Medical SciencesCompletedPrediction Hypothyroidism Patients Using Machine Learning Algorithms | Identification of Important Symptoms of HypothyroidismIran, Islamic Republic of
-
Kirsehir Ahi Evran UniversitesiCompleted
-
Changhua Christian HospitalCompleted
-
First Affiliated Hospital Xi'an Jiaotong UniversityCompletedPulmonary Hypertension | Acute Myocardial InfarctionChina
-
Aga Khan University Hospital, PakistanCompletedLeft Ventricle Non-compaction Cardiomyopathy
-
Yale-NUS CollegeCompletedADHD | Conduct Disorder | Oppositional Defiant Disorder
-
Tianjin Happy Life Technology Co., Ltd.Unknown