OncoTargets and therapy最新文献

Background: Kaposi sarcoma (KS) is a cutaneous neoplasm of endothelial origin. The causative agent is the human herpes virus-8 (HHV-8) which, combined with an immune system impairment, causes cell proliferation. To date, high-quality evidence and treatment recommendations for the management of KS are confined to the acquired immune deficiency syndrome (AIDS)-related KS, while the clinical approach to the treatment of classic KS (CKS) is based on small retrospective case series and the experience of clinicians in selected referral centers.

Materials and methods: A search of the English literature was conducted through PubMed/MEDLINE databases for studies regarding CKS diagnosis, staging, and treatment, published between January 1990 and September 2023.

Results: Overall, 122 out of 565 articles were selected. Based on the results of this literature review, we proposed indications regarding the recommended flow chart for diagnosis, staging, and follow-up of patients with CKS. We assess available evidences regarding topic, locoregional, and systemic treatments of CKS. We also provide a focus on novel treatment strategies and therapeutic approaches currently under evaluation in clinical trials.

Conclusion: CKS is a rare disease and its management requires a multidisciplinary assessment. Treatment in referral centers and enrolment in clinical trials might impact on outcomes.

Background: COL10A1 expression was up-regulated and could promote tumor development in pancreatic cancer. As a secreted protein, plasma COL10A1 level was proven to have certain diagnostic efficacy in gastric cancer, breast cancer, and colorectal cancer. It is still unknown whether it has a biomarker role for pancreatic cancer.

Aim: To explore and analyze the diagnostic and prognostic value of plasma COL10A1 level in pancreatic ductal adenocarcinoma (PDAC).

Method: The RNA-seq dataset of PDAC from The Cancer Genome Atlas (TCGA) and six expression profiling microarray datasets from Gene Expression Omnibus (GEO) were downloaded to analyze the expression of COL10A1 in tissues. Thirty-six patients with PDAC and eighteen healthy volunteers were enrolled to measure COL10A1 levels in tissues and plasmas, and the relationship between clinical characteristics and the COL10A1 levels was analyzed. The diagnostic and prognostic efficacy of plasma COL10A1 levels were calculated.

Results: Aspects of COL10A1 expression level in tissues, COL10A1 expression was significantly higher in PDAC tissue than adjacent normal tissue. The expression of COL10A1 was correlated with T, M, and AJCC stages. Patients with high COL10A1 expression had worse recurrence-free survival (RFS) and overall survival (OS) than those with low expression. Aspects of COL10A1 expression levels in plasma, its diagnostic area under the curve (AUC) for PDAC was 0.926 (95% CI 0.853-0.999), diagnostic sensitivity was 81% (95% CI 64-92%), and specificity was 100% (95% CI 81-100%). The time-dependent AUCs at 1-year and 3-year were 0.71 (95% CI 0.51-0.90) and 0.74 (95% CI 0.48-1.00), respectively.

Conclusion: In PDAC, plasma COL10A1 levels showed certain diagnostic and prognostic efficacy. COL10A1 may be a diagnostic and prognostic biomarker for PDAC and play a role in liquid biopsy of this disease.

Purpose: Gastric cancer (GC) is a disease with high prevalence and mortality, but we lack convenient and accurate methods to screen for this disease. Thus, we aimed to search for some salivary biomarkers and explore changes in metabolites in patients' saliva after radical gastrectomy.

Patients and methods: A total of 152 subjects were divided into three groups (healthy group, GC group, and one-week postoperative group). After simple processing, saliva samples were analyzed by liquid chromatography-mass spectrometry. First, we used total ion chromatography and principal component analysis to determine the metabolite profiles. Next, t-test, partial least squares discriminant analysis, support vector machine, and receiver operating characteristics curve analysis were performed to identify biomarkers. Then, Fisher discriminant analysis and hierarchical clustering analysis were performed to determine the discriminating ability of biomarkers. Finally, we established a generalized linear model to predict GC based on biomarkers, and used bootstrapping for internal validation.

Results: Between the healthy and GC groups, we identified four biomarkers: lactic acid, kynurenic acid, 3-hydroxystachydrine, and S-(1,2,2-trichlorovinyl)-L-cysteine. We used stepwise regression to select five metabolites and develop a model with areas under the curve equal to 0.973 in the training dataset and 0.924 in the validation dataset. Between the GC and one-week postoperative groups, we found two differential metabolites: 19-hydroxyprostaglandin E₂ and DG (14:0/0:0/18:2n6).

Conclusion: Differential metabolites were observed among the three groups. GC could be initially diagnosed on the basis of detection of these biomarkers. Moreover, changes in salivary metabolites in postoperative patients could provide important insights for basic studies.

Background: Mesothelioma is an uncommon malignant tumor with variable clinical presentations, radiological features, and morphological patterns. Mesothelioma with predominantly intrapulmonary growth presents with an insidious onset, similar radiological and even morphological features to lung cancer, and poses a diagnostic pitfall.

Case presentation: Herein, we reported a 53-year-old female with biphasic mesothelioma misdiagnosed as poorly differentiated adenocarcinoma with focal sarcomatoid carcinoma. Computed tomography (CT) scan of the chest at the first visit revealed a solid lobulated nodule in the basal segment of the lower lobe of the right lung, which was suspicious of lung cancer. Microscopically, the tumor was composed of epithelioid and spindle cells, both of which were diffusely and strongly positive for CK7, and negative for TTF-1, Napsin A, P40, Melan A, S-100, SMA, and CD34. It was originally misdiagnosed as poorly differentiated adenocarcinoma with focal sarcomatoid carcinoma at initial presentation. Until her second admission with the discovery of a nodule in the right diaphragmatic angle, the peculiar location and biphasic component reminded us of biphasic mesothelioma. Immunohistochemically, tumor cells in both pulmonary and diaphragmatic nodules were positive for calretinin, D2-40, and WT-1, but negative for BerEP4 and MOC31. The patient was treated with a chemotherapy regimen of pemetrexed and carboplatin. After 11 months of follow-up, the patient recovers well without recurrence or metastasis.

Conclusion: Mesothelioma with predominantly intrapulmonary growth is extremely rare and poses a diagnostic pitfall. For this entity, subtle morphological features, selection of immunohistochemical markers, and electron microscopy are of great significance for definite diagnosis.

Background: To identify biomarkers of papillary thyroid carcinoma (PTC) and explore the possible pathogenic mechanism.

Methods: This study included five patients with PTC. Protein expression of cancer tissues and adjacent normal thyroid tissues from each patient were analyzed by TMT proteomics technology. Differentially expressed proteins were identified, and functional annotation of differentially expressed proteins was performed by bioinformatics and pathway enrichment analysis.

Results: A total of 639 differentially expressed proteins were identified, including 278 upregulated and 361 downregulated proteins. Six upregulated proteins were identified as potential specific markers of PTC.

Conclusion: Differentially expressed proteins may represent new molecular markers of PTC. These differentially expressed proteins and the related pathways may provide new insights into the pathogenic mechanisms of PTC.

Background: KLF2 is a transcription factor expressed early in mammalian development that plays a role in many processes of development and disease. Recently, increasing studies revealed that KLF2 plays a key role in the occurrence and progression of cancer.

Purpose: The aim of this study was to explore the role of KLF2 in various tumor types using the Cancer Genome Atlas dataset.

Methods: Here, we set out to explore the role of KLF2 in 33 tumor types using TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) dataset, Human Protein Atlas (HPA), UALCAN database, CancerSEA, GSCALite and several bioinformatic tools. Furthermore, we also performed immunohistochemistry and qPCR to further validate the role of KLF2 in multiple cancers and its correlation with prognosis.

Results: We found that KLF2 was underexpressed in most tumors and generally predicted poor OS in tumor patients. We found that amplification of KLF2 may be a risk factor for patients with OV (Ovarian serous cystadenocarcinoma). We also analyzed the abundance of checkpoints and markers of specific immune subsets including CD8+ T lymphocytes (T cells), CD4+ T cells, macrophages, and endothelial cells that significantly correlated with the expression level of KLF2 in pan-carcinoma tissues. In some cancers, KLF2 expression levels are positively correlated with gene promoter DNA methylation and drug sensitivity. In addition, we found that KLF2 is involved in single-cell level cell invasion in some cancers. In addition, KLF2 is co-expressed with several intracellular signal transduction genes involved in immune system processes. Immunohistochemistry and qPCR confirmed the low expression of KLF2 in STAD (stomach adenocarcinoma) and renal cancer.

Conclusion: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles of KLF2 in multiple human cancers and can be regarded as a potential prognostic marker and a novel target for cancer immunotherapy.

Introduction: Advanced malignant melanoma is a very aggressive disease, historically with poor prognosis before the new advances with immunotherapy and targeted therapies that have changed the standard of care, especially in cutaneous melanoma. Peru has aggressive features such as higher rates of acral lentiginous melanoma (ALM) subtype with historically shorter survival.

Methods: This study describes Peruvian patients with advanced melanoma treated with immunotherapy (nivolumab) in two oncological institutions (public and private), including the discussion of the impact on overall survival (OS) divided by subtype (with incidence in ALM histology) and potential biomarkers that could be related to prognosis.

Results: We found that immunotherapy is safe, and improves progression-free survival (PFS), OS and objective response rate (ORR) in our patients, with lower benefit in ALM histology. No prognostic blood inflammatory biomarkers were detected.

Discussion: There is very limited data of Peruvian patients with metastatic melanoma treated with immunotherapy, especially the outcomes in ALM histology. Our goal is to share an example of the impact of immunotherapy in a Latin American (LATAM) population considered as an unsatisfied group with an enormous need of novel treatments and biomarkers.

Cholangiocarcinoma is a malignant tumor that affects the bile ducts and is usually aggressive with poor prognosis. The treatment of cholangiocarcinoma depends on the stage and location of the tumor as well as the patient's overall health status. Systemic therapy, such as chemotherapy using gemcitabine and cisplatin, is the first choice for patients with cholangiocarcinoma who were inoperable. After no response to first-line chemotherapy, second-line chemotherapy or targeted therapy focusing on signaling pathway inhibition are subsequent treatment. The present report described a case of cholangiocarcinoma involving bilateral lobes of liver. He received one cycle of chemotherapy with gemcitabine plus cisplatin and exhibited rapid progression. Next-generation sequencing was performed, and the results showed that MET amplification had a gene copy number of 68. After that, he underwent tepotinib and tumor shrinkage occurred. After a follow‑up period of 12 months, the treatment response was partial response, and the benefit of tepotinib is ongoing. The development of precision medicine has expanded the paradigm of targeted therapies to increasingly favorable options in the second line and beyond, and prolong overall survival. Detecting druggable mutations (mutations potentially amenable to treatment with) for identifying a landscape of therapeutic options is imperative for managing cholangiocarcinoma.

Purpose: Hydrogen (H₂) gas inhalation might alleviate acute radiotherapy toxicities by scavenging free radicals produced by ionizing radiation and anti-inflammatory properties. This study aimed to investigate the feasibility and safety of H₂ gas inhalation during concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck cancer (LAHNC).

Patients and methods: We designed a pilot prospective study combining CCRT with aerosol inhalation of H₂ gas. Each patient was scheduled to receive daily intensity-modulated radiotherapy (IMRT) in 33 fractions on a weekday and six cycles of weekly chemotherapy. All patients inhaled H₂ gas through a cannula or mask 1 hour per day, 1-2 hours before IMRT. The primary endpoint was the feasibility of H₂ inhalation. Eighty percent of the patients who completed at least 20 applications of H₂ gas inhalation were considered feasible. The secondary endpoints were safety profiles during H₂ gas inhalation (vital signs and symptoms related to H₂ gas inhalation) and acute toxicities during CCRT.

Results: We enrolled 10 patients with LAHNC between July 2023 and December 2023. All patients received 33 fractions of H₂ gas inhalation on the same day as the IMRT. Vital signs during and at the end of H₂ gas inhalation were stable in all patients. None of the 10 patients had hypertension or hypotension during any of the 33 inhalations. No adverse events related to H₂ gas inhalation, such as cough, nasal bleeding, dizziness, headache, nausea, or vomiting, were reported. Grade 3 leukopenia was found in two patients (20%) during the 5th week of CCRT. Grade 2 radiation dermatitis and pharyngitis were found in three patients (30%).

Conclusion: H₂ gas inhalation combined with CCRT is feasible and safe for patients with LAHNC.

Purpose: Cutaneous squamous cell carcinoma (cSCC) ranks as the second most common malignancy in clinical practice and poses a significant threat to public health due to its high malignancy. In this study, we aimed to explore potential biomarkers and molecular mechanisms of cSCC.

Methods: Differentially expressed genes (DEGs) from GSE66359 and GSE117247 datasets were identified using R software. We conducted enrichment analyses and screened hub genes through protein-protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA). To assess the diagnostic performance of these genes, we generated ROC curves using both internal and external datasets (GSE45164) and validated the expression levels of these genes in cSCC tissues through immunohistochemistry. Subsequently, we predicted the target miRNAs and lncRNAs for hub genes using online databases and constructed competing endogenous RNA (ceRNA) networks.

Results: In total, we identified 505 upregulated DEGs and 522 downregulated DEGs. Through PPI and WGCNA analyses, we identified four hub genes exhibiting robust diagnostic performance in internal and external datasets (AUC > 0.9) and selected three previously unreported genes for further analysis. Immunohistochemistry demonstrated significantly elevated CCNA2, CCNB2, and UBE2C expression in cSCC tissues compared to normal skin tissues. Finally, we constructed three ceRNA networks, namely NEAT1/H19-hsa-miR-148a-3p-CCNA2 and NEAT1-hsa-miR-140-3p-UBE2C.

Conclusion: In conclusion, we have identified CCNA2, CCNB2, and UBE2C as novel biomarkers for cSCC, and the NEAT1/H19-hsa-miR-148a-3p-CCNA2 and NEAT1-hsa-miR-140-3p-UBE2C ceRNA networks may represent molecular mechanisms under-lying cSCC progression. The findings of this study offer new diagnostic and therapeutic options for cSCC patients.