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HNRNPC as a pan-cancer biomarker and therapeutic target involved in tumor progression and immune regulation

oncology research 2025年第1期33卷 83-102页

作者： Yuezhou Zhang Zhao Zhang Jinxin Dong Changan Liu department of hepatobiliary surgery The Second Affiliated Hospital of Chongqing Medical University Chongqing 400016 China. department of hepatobiliary surgery The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China.

Background:Aberrant expression of RNA-binding proteins (RBPs) has been linked to a variety of diseases, including hematological disorders, cardiovascular diseases, and multiple types of cancer. Heterogeneous nuclear ribonucleoprotein C (HNRNPC), a member belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family, plays a pivotal role in nucleic acid metabolism. Previous studies have underscored the significance of HNRNPC in tumorigenesis; however, its specific role in malignant tumor progression remains inadequately characterized.Methods:We leveraged publicly available databases, including The Cancer Genome Atlas (TCGA), to explore the potential involvement of HNRNPC across various cancers. Additionally, we performed experimental validation studies focused on liver cancer.Results:Our analysis revealed that HNRNPC is overexpressed in a wide range of common malignancies, including liver and lung cancers, and is strongly linked to unfavorable outcomes. Furthermore, HNRNPC was observed to be closely linked to tumor immunity. Through immune checkpoint analysis and immune cell infiltration assessment, HNRNPC emerged as a potential target for modulating tumor immunotherapy. Notably, silencing of HNRNPC markedly inhibited the proliferation, metastasis, and infiltration of liver cancer cells.Conclusion:In summary, our findings highlight HNRNPC as a prognostic marker in various cancers, including liver cancer, and suggest its involvement in shaping the tumor immune microenvironment. These insights offer potential avenues for improving clinical outcomes in tumors with elevated HNRNPC expression, particularly through immunotherapeutic strategies.

关键词： Hepatocellular carcinoma Heterogeneous nuclear ribonucleoprotein C (HNRNPC) Immunotherapeutic target Pan-cancer analysis Prognostic biomarker Tumor immunity

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Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu department of hepatobiliary and Pancreatic surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ Transplantation Key Laboratory of Integrated oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital department of hepatobiliary and Pancreatic surgery The First Affiliated HospitalZhejiang University School of Medicine department of Urology The Second Affiliated HospitalZhejiang University School of Medicine department of hepatobiliary and Pancreatic surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Liver regeneration using decellularized splenic scaffold: a novel approach in tissue engineering

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hepatobiliary & Pancreatic Diseases International 2015年第5期14卷 502-508页

作者： Jun-Xi Xiang Xing-Long Zheng Rui Gao Wan-Quan Wu Xu-Long Zhu Jian-Hui Li Yi Lv department of hepatobiliary surgery First Affiliated Hospital of Xi'an Jiaotong University department of surgical oncology Shaanxi Provincial People's Hospital

BACKGROUND： The potential application of decellularized liver scaffold for liver regeneration is limited by severe shortage of donor organs. Attempt of using heterograft scaffold is accompanied with high risks of zoonosis and immunological rejection. We proposed that the spleen, which procured more extensively than the liver, could be an ideal source of decellularized scaffold for liver regeneration. METHODS： After harvested from donor rat, the spleen was processed by 12-hour freezing/thawing ×2 cycles, then circulation perfusion of 0.02% trypsin and 3% Triton X-100 sequentially through the splenic artery for 32 hours in total to prepare decellularized scaffold. The structure and component characteristics of the scaffold were determined by hematoxylin and eosin and immumohistochemical staining, scanning electron microscope, DNA detection, porosity measurement, biocompatibility and cytocompatibility test. Recellularization of scaffold by 5×106 bone marrow mesenchymal stem cells（BMSCs） was carried out to preliminarily evaluate the feasibility of liver regeneration by BMSCs reseeding and differentiation in decellularized splenic ***： After decellularization, a translucent scaffold, which retained the gross shape of the spleen, was generated. Histological evaluation and residual DNA quantitation revealed the remaining of extracellular matrix without nucleus and cytoplasm residue. Immunohistochemical study proved the existence of collagens I, IV, fibronectin, laminin and elastin in decellularized splenic scaffold, which showed a similarity with decellularized liver. A scanning electron microscope presented the remaining three-dimensional porous structure of extracellular matrix and small blood vessels. The poros-ity of scaffold, aperture of 45.36±4.87 μm and pore rate of 80.14%±2.99% was suitable for cell engraftment. Subcutaneous implantation of decellularized scaffold presented good histocompatibility, and recellularization of the splenic scaffold demonstr

关键词： tissue engineering liver regeneration decellularized scaffold spleen bone marrow mesenchymal stem cells

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Potential prognostic biomarkers in pancreatic juice of resectable pancreatic ductal adenocarcinoma

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World Journal of Clinical oncology 2017年第3期8卷 255-260页

作者： Shefali Agrawal hepatobiliary and Pancreatic surgery Department of Surgical OncologyIndraprastha Apollo Hospitals

Despite potentially curative surgery pancreatic cancer has a dismal *** cancer antigen 19-9(CA 19-9) correlates with tumor burden,resectability and survival in patients with pancreatic ductal *** of novel biomarkers may facilitate early diagnosis of pancreatic cancer and improve *** juice is a rich source of cancer-specific proteins rendering it a promising tool for identifying *** proteomic and micro RNA expression analyses have identified several biomarkers of potential diagnostic and prognostic *** markers CA 19-9 and carcinoembryonic antigen(CEA) are widely used in the characterization of premalignant and malignant lesions of the *** level of CEA in bile is a marker for malignancy and a predictor of hepatic *** potential value of CA 19-9,CEA and lactate dehydrogenase as prognostic biomarkers in pancreatic juice and bile is *** of pancreatic juice and bile can be readily collected during surgical resection of the *** of pancreatic juice and bile to identify novel prognostic biomarkers may improve selection of patients for adjuvant therapy with a favorable impact on overall survival in patients diagnosed with pancreatic cancer.

关键词： Prognostic biomarkers Pancreatic juice Bile Pancreatic adenocarcinoma surgery

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Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

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World Journal of Clinical Cases 2025年第2期13卷 14-20页

作者： Aikaterini Mastoraki Maria Tsamopoulou Foivos-Konstantinos Stamatis Alexios Strimpakos Ero Mouchtouri Christiana Panagi Evgenia Mela Sotiria Mastoraki Aristotelis Kechagias Dimitrios Schizas department of surgery National and Kapodistrian University of AthensLaikon General HospitalAthens 11527Greece department of surgery National and Kapodistrian University of AthensAthens 11527Greece department of Medical oncology Hygeia HospitalAthens 15123Greece department of Radiology Henry Dunant Hospital CenterAthens 11526Greece department of surgery Athens Metropolitan HospitalAthens 15562Greece

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast *** is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition *** cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic *** recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative *** CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always ***,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone ***,surgical removal of breast CS does not necessarily ensure patient’s long-term ***,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is ***,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment *** aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological *** features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

关键词： Carcinosarcoma Breast Diagnostic approach Therapeutic management Prognostic parameters

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Effects of partial portal vein arterialization on the hilar bile duct in a rat model

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hepatobiliary & Pancreatic Diseases International 2011年第5期10卷 533-538页

作者： Shao-Hua Guo, Chong-Hui Li,Yong-Liang Chen, Jian-Ning Song,Ai-Qun Zhang and Cheng Zhou department of hepatobiliary surgery (Guo SH, Li CH, Chen YL, Song JN, Zhang AQ and Zhou C) and department of surgical oncology (Guo SH), General Hospital of PLA, Beijing 100853, China [a] department of hepatobiliary surgery General Hospital of PLA Beijing 100853 China [b] department of surgical oncology General Hospital of PLA Beijing 100853 China

BACKGROUND: Liver revascularization is frequently required during the enlarged radical operation for hilar cholangio carcinoma involving the hepatic artery. Researchers have carried out a number of experiments applying partial porta vein arterialization (PVA) in clinical practice. In this study we aimed to establish a theoretical basis for clinical application o partial PVA and to investigate the effects of partial PVA on ra hilar bile duct and hepatic functions. METHODS: Thirty rats were randomly and equally assigned into 3 groups: control (group A), hepatic artery ligation+bile duct recanalization (group B), and partial PVA+bile duc recanalization (group C). Proliferation and apoptosis o rat hilar bile duct epithelial cells, arteriolar counts of the peribiliary plexus (PBP) of the bile duct wall, changes in serum biochemistry, and pathologic changes in the bile duc were assessed 1 month after operation. RESULTS: The proliferation of hilar bile duct epithelial cells in group B was greater than in groups A and C (P0.05), but the coun was lower in group B than in group A (P<0.01). No statistically significant differences in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin were found in the 3 groups. The gamma-glutamyltransferase value was higher in group B than in groups A and C (P<0.01) The hepatic tissues of groups A and C showed no significan abnormality. Chronic inflammatory changes in the hilar bile duct walls were observed only in group B. CONCLUSION: Partial PVA can restore the arterial blood supply of the hilar bile duct and significantly extenuate the injury to hilar bile duct epithelial cells resulting from hepatic artery ligation.

关键词： portal vein arterialization biliary epithelial cells peribiliary plexus

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Utility of routine blood tests after elective laparoscopic cholecystectomy for symptomatic gallstones

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World Journal of Gastrointestinal surgery 2017年第6期9卷 149-152页

作者： Offir Ben-Ishay Marina Zeltser Yoram Kluger surgical oncology Pancreatic and Hepatobiliary Surgery ServiceDepartment of General SurgeryDivision of SurgeryRambam Health Care CampusHaifa 35254Israel

AIM To evaluate the value of blood testing after elective laparoscopic cholecystectomy and its association with procedure related *** Charts of all patients undergoing elective laparoscopic cholecystectomy from January 2013 through December2014 were reviewed retrospectively for demographics,indication for surgery,operative course and *** our institution the decision to perform postoperative blood analysis is left for the discretion of the surgeon,therefore we had the possibility to compare the results of those who had blood analyses results to those who did *** was performed to identify variables associated with the decision to perform postoperative blood *** a univariate and multivariate analyses was performed comparing the two *** subgroup analysis was performed to identify factors associated with procedure related *** Five hundred and thirty-two elective laparoscopic cholecystectomies for symptomatic gallstones were performed during the study ***-four percent of the patients(n=340)had blood tests taken post *** that had laboratory tests taken were older(P=0.006,OR=1.01),had longer surgery(P<0.001,OR=3.22)had more drains placed(P<0.001,OR=3.2)and stayed longer in the hospital(P<0.001,OR=1.2).A subgroup analysis of the patients who experienced complications revealed longer stay in the hospital(P<0.001),higher body mass index(BMI)(P=0.04,OR=1.08),increased rates of drain placement(P=0.006,OR=3.1)and higher conversion rates(P=0.01,OR=14.6).Postoperative blood tests withdrawals were not associated with complications(P=0.44).On Multivariate analysis BMI and drain placement were independently associated with *** The current study indicate that routine postoperative blood tests after elective laparoscopic cholecystectomy for symptomatic gallstones does not predict complications and may have an added benefit in diagnosis and management of cases w

关键词： Cholecystectomy Blood tests Laparoscopy Complications Post-operative Gallstones symptomatic

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Current treatment options for colon cancer peritoneal carcinomatosis

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World Journal of Gastroenterology 2014年第35期20卷 12493-12500页

作者： Tomoyoshi Aoyagi Krista P Terracina Ali Raza Kazuaki Takabe Division of surgical oncology Department of SurgeryVirginia Commonwealth University School of Medicine Division of surgical oncology Department of SurgeryVirginia Commonwealth University School of MedicineRichmond

Peritoneal carcinomatosis(PC),the dissemination of cancer cells throughout the lining of the abdominal cavity,is the second most common presentation of colon cancer distant *** remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years,it has been repeatedly shown that these therapies remain ineffective for colon cancer ***,there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC) prolongs the life of colon cancer PC ***,we will review the clinical presentation,the mechanisms of disease progression,and current treatment options for colon cancer PC,with a focus on the benefits and limitations of CRSHIPEC.

关键词： Cancer Colorectal Carcinomatosis Peritoneal Hyperthermic intraperitoneal chemotherapy Intraperitoneal chemotherapy Cytoreductive surgery Mechanism

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Immunohistochemical analysis of the Wnt/β-catenin signaling pathway in pancreatic neuroendocrine neoplasms

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World Journal of Gastrointestinal oncology 2016年第8期8卷 615-622页

作者： Vivian Weiss Julie Dueber Jesse P Wright Justin Cates Frank Revetta Alexander A Parikh Nipun B Merchant Chanjuan Shi department of Pathology Microbiology and Immunology Vanderbilt University Medical Center department of surgery Surgical Oncology Vanderbilt University Medical Center department of surgery Surgical Oncology University of Miami Hospital

AIM: To investigate the role of the Wnt/β-catenin pathway in pancreatic neuroendocrine neoplasms(PanN ENs). METHODS: Tissue microarrays containing 88 PanN ENs were immunohistochemically labeled with antibodies to β-catenin, E-cadherin, adenomatous polyposis coli(APC), chromogranin and synaptophysin. One case had only metastatic tumors resected, whereas others(n = 87) received pancreatectomy with or without partial hepatectomy. Pathology slides, demographic, clinicopathologic, and follow up data were reviewed. Patients' demographics, clinicopathologic features, and immunohistochemical results from 87 primary tumors were compared between patients with low stage(stage Ⅰ/Ⅱ) and high stage(stage Ⅲ/Ⅳ) tumors. In addition, correlation of immunohistochemical results from primary tumors with disease-specific survival(DSS) was evaluated. RESULTS: Strong membranous β-catenin staining in the primary tumor was observed in all 13 stage Ⅲ/Ⅳ Pan NENs as compared to 47%(35/74) of stage Ⅰ/Ⅱtumors(P < 0.01). However, the strong membranous β-catenin staining was unassociated with tumor grade or DSS. Decreased membranous β-catenin staining was associated with decreased membranous E-cadherin labeling. Nuclear β-catenin staining was seen in 15%(2/13) of stage Ⅲ/Ⅳ Pan NENs as compared to 0%(0/74) of stage Ⅰ/Ⅱ tumors(P = 0.02). The case with metastasectomy only also showed nuclear β-catenin staining. Two of the three cases with nuclear β-catenin staining were familial adenomatous polyposis(FAP) patients. Lack of APC expression was seen in 70%(57/81) of the cases, including the 3 cases with nuclear β-catenin staining. Expression of E-cadherin and APC in primary tumor was not correlated with tumor grade, tumor stage, or disease specific survival. CONCLUSION: The Wnt/β-catenin pathway was altered in some PanN ENs, but did not Impact DSS. PanN ENs in FAP patients demonstrated nuclear β-catenin accumulation and loss of APC.

关键词： β-catenin Familial adenomatous polyposis Pancreatic neuroendocrine neoplasm Adenomatous polyposis coli E-cadherin

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Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

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World Journal of Gastroenterology 2018年第2期24卷 274-289页

作者： Rossella Reddavid Silvia Sofia Paolo Chiaro Fabio Colli Renza Trapani Laura Esposito Mario Solej Maurizio Degiuli surgical oncology and Digestive surgery Department of Oncology University of Turin San Luigi University Hospital department of surgical Sciences Digestive and Oncological Surgery University of Turin Molinette Hospital

AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 *** We proceeded to a review of the literature with Pub Med, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials(RCTs) comparing NAC followed by surgery(NAC + S) with surgery alone(SA) for gastric cancer(GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association(JGCA) performed in both arms, disease-specific(DSS) and disease-free survival(DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment. RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S(n = 1089) with SA(n = 973) published in the period from January 1993-March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node(LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. Inthe third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the "Study Treatment" protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction(EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper

关键词： gastric cancer neoadjuvant chemotherapy perioperative chemotherapy D2 lymphadenectomy randomized control trial

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