Clinical trial NCT06778538: Evaluation of HPGD and SCLO2A1 Expression in Clear Cell Renal Cell Carcinoma Patients
Official title: HPGD Overexpression Attenuates Tumorigenesis and EMT in Clear Cell Renal Cell Carcinoma by Upregulating SLCO2A1
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Clear Cell Renal Cell Carcinoma (ccRCC)
Keywords: HPGD
clear cell renal cell carcinoma
biomarker
prognosis
EMT
tumorigenesis
SLCO2A1
Lead sponsor: Lanzhou University Second Hospital
Sponsor class: OTHER
Collaborators: name: Lanzhou University Second Hospital
First posted: 2025-01-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of adult patients aged 18 years or older with a confirmed diagnosis of clear cell renal cell carcinoma. Participants will be recruited from oncology clinics and hospitals, and all eligible individuals must have measurable disease as defined by RECIST criteria. Both male and female participants will be included, with no restrictions based on ethnicity or socioeconomic background. Participants will be required to provide informed consent and meet the inclusion criteria related to health status and prior treatments.

Brief summary: This study aims to investigate the role of HPGD in clear cell renal cell carcinoma (ccRCC). Specifically, it will focus on HPGD's impact on proliferation, epithelial-mesenchymal transition (EMT), and prognosis. The study will analyze gene expression data from clinical samples and use techniques like RT-qPCR, Western blotting, and immunohistochemistry to assess HPGD expression levels. Additionally, the research will explore the relationship between HPGD and patient survival outcomes. By elucidating HPGD's contribution to cancer progression, the study seeks to identify potential therapeutic targets for improving renal cancer treatment.

Detailed description: This study is designed to comprehensively explore the role of 15-hydroxyprostaglandin dehydrogenase ( HPGD) in clear cell renal cell carcinoma development and progression. HPGD has been implicated in various cancers, with evidence suggesting its involvement in tumorigenesis, EMT, and poor prognosis. However, its specific function n clear cell renal cell carcinoma (ccRCC) is still unclear. This research will analyze clinical samples, including tumor tissues and normal adjacent tissues, to evaluate HPGD expression through a combination of advanced laboratory techniques such as quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC) and RNA sequencing.

Furthermore, HPGD-interacting proteins were predicted using STRING and TCGA data, followed by PCR, Western blot validation, and IHC. Mechanistically, HPGD positively correlated with the solute carrier organic anion transporter 2A1 (SLCO2A1), and SLCO2A1 knockdown partially attenuated the tumor-suppressive effects of HPGD overexpression..

This study underscores the tumor-suppressive role of HPGD in ccRCC, highlighting its capacity to hinder cell proliferation and EMT via its interaction with SLCO2A1. Targeting the HPGD-SLCO2A1 axis may offer a promising novel therapeutic approach for ccRCC management.

Eligibility criteria: Inclusion Criteria:

Adults aged 18 years or older. Histologically confirmed diagnosis of clear cell renal cell carcinoma . Measurable disease as per RECIST criteria. Adequate organ function as defined by laboratory tests (e.g., liver, kidney, and hematologic function).

HPGD expression level determined via biopsy or previous analysis. Written informed consent provided.

Exclusion Criteria:

History of other malignancies within the past 5 years, excluding non-melanoma skin cancer or in situ carcinoma.

Prior treatment with HPGD inhibitors or similar targeted therapies. Active or uncontrolled infections. Pregnant or breastfeeding women. Known autoimmune disorders or conditions requiring immunosuppressive therapy. Inability to comply with the study protocol or procedures.

Primary outcomes:
measure: HPGD Expression Levels in clear cell renal cell carcinoma（ccRCC） Patients
timeFrame: 2024.1-2024.6
Secondary outcomes:
Other outcomes:
Locations:
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
Study officials:
References:
citation: Monteleone NJ, Moore AE, Iacona JR, Lutz CS, Dixon DA. miR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon cancer. Sci Rep. 2019 Apr 1;9(1):5405. doi: 10.1038/s41598-019-41862-2.
citation: Arima K, Komohara Y, Bu L, Tsukamoto M, Itoyama R, Miyake K, Uchihara T, Ogata Y, Nakagawa S, Okabe H, Imai K, Hashimoto D, Chikamoto A, Yamashita YI, Baba H, Ishimoto T. Downregulation of 15-hydroxyprostaglandin dehydrogenase by interleukin-1beta from activated macrophages leads to poor prognosis in pancreatic cancer. Cancer Sci. 2018 Feb;109(2):462-470. doi: 10.1111/cas.13467. Epub 2018 Jan 27.
citation: Myung SJ, Rerko RM, Yan M, Platzer P, Guda K, Dotson A, Lawrence E, Dannenberg AJ, Lovgren AK, Luo G, Pretlow TP, Newman RA, Willis J, Dawson D, Markowitz SD. 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12098-102. doi: 10.1073/pnas.0603235103. Epub 2006 Jul 31.
citation: Wolf I, O'Kelly J, Rubinek T, Tong M, Nguyen A, Lin BT, Tai HH, Karlan BY, Koeffler HP. 15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer. Cancer Res. 2006 Aug 1;66(15):7818-23. doi: 10.1158/0008-5472.CAN-05-4368.