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Zhao W, Wang Y, Zhu J, Arya S, Huang G, Li S, Chen Q, Liu X, Yuan J, Jia J. Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening. Sci Rep 2025; 15:9180. [PMID: 40097576 PMCID: PMC11914096 DOI: 10.1038/s41598-025-93167-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 03/05/2025] [Indexed: 03/19/2025] Open
Abstract
Osteosarcoma, the most common primary bone cancer in children and adolescents, presents significant challenges, particularly in metastasis and recurrence, resulting in poor survival rates. This study explores the role of PANoptosis-a complex cell death mechanism involving pyroptosis, apoptosis, and necroptosis-in osteosarcoma by identifying relevant long non-coding RNAs (lncRNAs) and their prognostic significance. Bioinformatics analyses used RNA expression data from the GEO and TARGET databases to identify differentially expressed genes (DEGs) and PANoptosis-related genes (PRGs). Co-expression analysis revealed lncRNAs linked to PRGs, forming a risk prognostic model. Five PRGs and two lncRNAs were significantly associated with prognosis, with the model showing high predictive accuracy (AUC 0.876, 0.787, and 0.794 for 1, 3, and 5 years). Notably, lncRNA AC133552.2 was downregulated in osteosarcoma tissues, correlating with poor survival and reduced immune infiltration. Silencing AC133552.2 promoted cell proliferation and migration, while overexpression inhibited tumor growth and metastasis, confirmed in xenograft models. AC133552.2 emerges as a potential biomarker and therapeutic target, with future research needed to explore its molecular mechanisms and clinical application.
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Affiliation(s)
- Wenrui Zhao
- Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, Jiangxi, China
| | - Yameng Wang
- Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, Jiangxi, China
| | - Junchao Zhu
- Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, Jiangxi, China
| | - Shahrzad Arya
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Guowen Huang
- Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, Jiangxi, China
| | - Shengqin Li
- Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, Jiangxi, China
| | - Qi Chen
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xijuan Liu
- Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jinghong Yuan
- Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China.
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, Jiangxi, China.
| | - Jingyu Jia
- Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China.
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, Jiangxi, China.
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Schroder PM, Biesterveld BE, Al-Adra DP. Premalignant Lesions in the Kidney Transplant Candidate. Semin Nephrol 2024; 44:151495. [PMID: 38490902 DOI: 10.1016/j.semnephrol.2024.151495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2024]
Abstract
End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the shortage of available organs. Although management and surveillance guidelines exist for malignancies identified in the transplant and waitlist populations, less is written about the management of premalignant lesions in this population. This review covers the less common premalignant lesions (intraductal papillary mucinous neoplasm, gastrointestinal stromal tumor, thymoma, and pancreatic neuroendocrine tumor) that can be found in the transplant candidate population. High-level evidence for the management of these rarer premalignant lesions in the transplant population is lacking, and this review extrapolates evidence from the general population and should not be a substitute for a multidisciplinary discussion with medical and surgical oncologists.
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Affiliation(s)
- Paul M Schroder
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Ben E Biesterveld
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - David P Al-Adra
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI.
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Stammler R, Anglicheau D, Landi B, Meatchi T, Ragot E, Thervet E, Lazareth H. Gastrointestinal tumors in transplantation: Two case reports and review of literature. World J Gastroenterol 2022; 28:5076-5085. [PMID: 36160649 PMCID: PMC9494929 DOI: 10.3748/wjg.v28.i34.5076] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/19/2022] [Accepted: 08/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. As most of them harbor a KIT mutation (75%), selective kinase inhibitors are the therapeutic option and show a sustained objective response among patients with metastatic or unresectable GISTs. A well-known higher risk of neoplasm has been described among renal transplant recipients (RTRs). Nevertheless, only few cases of GIST onset among transplant patients have been reported in the literature. CASE SUMMARY Here, we describe 2 cases of gastric GIST occurring during the follow-up of RTRs. We also review the existing literature concerning GIST occurrence in transplant patients. In total and in association with our 2 cases, 16 patients have been reported. The median age was 59.5 years and 69% were male. With a median tumor size of 45 mm, no patient displayed metastatic dissemination at diagnosis. Time from transplantation to diagnosis was highly variable between 5 mo and 21 years. Histopathological data mostly revealed high risk of progression (43%). Death increased to 29% during follow-up. Surgical treatment was systematically performed when the tumor was operable (94%). The use of adjuvant therapy was uncommon (19%). CONCLUSION GISTs represent rare but potentially severe malignant complication among transplant patients.
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Affiliation(s)
- Romain Stammler
- Department of Nephrology, Georges Pompidou European Hospital, Paris 75015, France
| | - Dany Anglicheau
- Department of Renal Transplantation, Necker-Enfants Malades Institute, French National Institutes of Health and Medical Research U1151, Paris 75015, France
- Université Paris Cité, Assistance Publique des Hôpitaux de Paris, Paris 75001, France
| | - Bruno Landi
- Université Paris Cité, Assistance Publique des Hôpitaux de Paris, Paris 75001, France
- Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Paris 75015, France
| | - Tchao Meatchi
- Department of Pathology, Georges Pompidou European Hospital, Paris 75015, France
| | - Emilia Ragot
- Department of Digestive Surgery, Georges Pompidou European Hospital, Paris 75015, France
| | - Eric Thervet
- Department of Nephrology, Georges Pompidou European Hospital, Paris 75015, France
- Université Paris Cité, Assistance Publique des Hôpitaux de Paris, Paris 75001, France
| | - Hélène Lazareth
- Department of Nephrology, Georges Pompidou European Hospital, Paris 75015, France
- Université Paris Cité, Assistance Publique des Hôpitaux de Paris, Paris 75001, France
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Fernández JÁ, Alconchel F, Gómez B, Martínez J, Ramírez P. Unresectable GIST liver metastases and liver transplantation: A review and theoretical basis for a new indication. Int J Surg 2021; 94:106126. [PMID: 34592432 DOI: 10.1016/j.ijsu.2021.106126] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 09/16/2021] [Accepted: 09/20/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Liver metastases from gastrointestinal stromal tumors (GIST) can be found synchronously to a primary tumor and in the medium/long term after resection of a high-risk GIST. In these cases, treatment with tyrosine kinase inhibitors like imatinib has provided good results, but drug resistance is common after two years of treatment. Liver resection of potentially resectable metastases can improve the results of medical treatment. In cases of unresectability, the role of liver transplantation (LT) has not been well-studied. MATERIALS AND METHODS A review of the literature was undertaken from January 1995 to December 2020 following the PRISMA and AMSTAR guidelines. RESULTS Fifteen cases were identified. In eight cases, the LT was carried out before 2002. Mutational status was only studied in seven cases. LT was performed in 12 cases with a deceased donor and in three cases with a living donor. After a mean follow-up of 52.4 months, overall survival was 86.6% with disease-free survival of 53.3% CONCLUSION: LT in the management of unresectable GIST metastases has rarely been performed. Although its application has a solid theoretical basis, its use understood as a radical extension of a standard resection can only be recommended within prospective studies by groups with considerable experience in both GIST and transplantation care.
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Affiliation(s)
- Juan Ángel Fernández
- Department of Surgery and Organ Transplantation. Virgen de la Arrixaca University Hospital. Ctra. Madrid-Cartagena s/n, 30120 Murcia Spain Department of Clinical Oncology. Virgen de la Arrixaca University Hospital. Ctra. Madrid-Cartagena s/n, 30120 Murcia Spain Biomedical Research Institute of Murcia (IMIB-Arrixaca). Campus de Ciencias de la Salud. Ctra. Buenavista s/n, 30120 Murcia Spain
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Juric I, Basic-Jukic N. Multiple Primary Malignancies: The First Case of a Combination of a Gastrointestinal Stromal Tumor and Renal Cell Carcinoma in a Kidney Transplant Recipient. Transplant Proc 2019; 51:3070-3071. [PMID: 31611119 DOI: 10.1016/j.transproceed.2019.04.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 04/05/2019] [Indexed: 10/25/2022]
Abstract
There is limited data on multiple primary malignancies in the kidney transplant population. Gastrointestinal stromal tumors (GISTs) are rare tumors in kidney transplant recipients, with only 5 cases reported in the literature to date. GIST patients are at an increased risk for developing additional malignancies, with other histologic types of gastrointestinal tract malignancies being the most frequent and other types of malignancies rare. There is evidence in the literature suggesting an association between GIST and renal cell carcinomas. We report on the first case of a GIST and a renal cell carcinoma in a kidney transplant recipient and in other solid organ transplant recipients.
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Affiliation(s)
- Ivana Juric
- Department of Nephrology, Arterial Hypertension, Dialysis, and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Nikolina Basic-Jukic
- Department of Nephrology, Arterial Hypertension, Dialysis, and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
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Small intestinal perforation due to a huge gastrointestinal stromal tumor in a kidney transplant recipient: a case report and literature review. BMC Nephrol 2019; 20:120. [PMID: 30943904 PMCID: PMC6448240 DOI: 10.1186/s12882-019-1310-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 03/21/2019] [Indexed: 12/16/2022] Open
Abstract
Background Gastrointestinal stromal tumors (GISTs) in transplant recipients are very rare and only a handful of cases have been reported to date. Here we present the first known case of a huge GIST in a kidney transplant recipient with perforation of small intestine. Case presentation A 64-year-old male presented at our hospital with right colic pain; he had received an ABO incompatible kidney transplant 6 years earlier and was treated with cyclosporine, mycophenolate mofetil, and methylprednisolone. Radiological evaluation revealed a huge (11 cm in diameter) solitary tumor at the small intestine without distant metastasis. The small intestinal wall at the tumor location was perforated one week after diagnosis and the patient underwent emergency surgery. The pathological findings were compatible with GIST and the tumor consisted of spindle cells with positive staining for KIT, CD34, and DOG1 and negative or weak staining for desmin and S-100 protein. A mutation in exon 11 of the c-kit gene was also detected. Cyclosporine was withdrawn and imatinib mesylate (400 mg daily) was introduced. However, thereafter, we needed to decrease the dose at 300 mg daily due to severe hyponatremia. Reduced imatinib treatment was well tolerated and recurrence was not observed for 18 months after surgery. Conclusions The occurrence of GISTs in transplant patients is rare, and huge GISTs should be resected immediately after diagnosis because gastrointestinal tract at the tumor site could be perforated. Imatinib treatment is feasible in transplant recipients under immunosuppression, although immunosuppressive drugs metabolized by CYP3A4 should be used at a reduced dosage or withdrawn.
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