World journal of clinical oncology最新文献

Background: Laryngeal squamous cell carcinoma (LSCC) is a prevalent head and neck malignancy with suboptimal survival rates due to late detection and therapeutic resistance.

Aim: To investigate chaperonin-containing TCP1 subunit 3 (CCT3) expression and its clinical implications, and its effects on LSCC cell growth.

Methods: Systematic data on CCT3 mRNA expression were collected from biomedical databases, and integrated further based on the standardized mean difference and the summary receiver operating characteristic curve. Single-cell RNA-seq data were mined to validate the expression level of CCT3 mRNA. In-house immunohistochemistry was performed to explore the CCT3 protein levels of clinical LSCC samples and their relationship with clinical parameters. The growth function of LSCC cell was analyzed using CRISPR knockout screening. CCT3-related signaling pathway analyses were conducted using gene set enrichment analysis. Protein-protein interaction network construction was performed to identify hub genes.

Results: CCT3 mRNA was significantly overexpressed in 269 LSCC tissues cases across multiple independent datasets (standardized mean difference = 32, area under the curve = 0.93); At the translational level, the in-house immunohistochemical analysis further demonstrated the consistent upregulation of CCT3 protein in 88 cases of LSCC samples (58 non-LSCC samples vs 30 LSCC samples, P = 1.4e^-14). Analysis of clinical parameters showed no significant differences among subgroup. Functional characterization with clustered regularly interspaced short palindromic repeats--mediated gene knockout revealed that depletion of CCT3 potently suppressed LSCC cell viability in vitro. Gene set enrichment analysis indicated that CCT3 was markedly associated with several key oncogenic pathways, including extracellular matrix receptor interaction and cell cycle regulation pathways.

Conclusion: CCT3 upregulation in LSCC may influence cellular growth by regulating related pathways, indicating its potential as a biomarker and therapeutic target for LSCC.

Genitourinary neoplasms, including bladder, prostate, renal, and testicular cancers, represent 25% of all solid tumors worldwide. Great advances have been achieved in the last few decades in diagnostic and therapeutic modalities. Among these, liquid biopsy (LB) technology has evolved during the past few years and offers emerging and novel modalities in the field of oncology. LB is performed by withdrawing bodily fluids (i.e., blood or urine) and looking for circulating tumor DNA, circulating tumor cells, extracellular vesicles, and non-coding RNAs, among others. Over the past years, several technologies have been developed to isolate and analyze the tumor burden. LB is less invasive than traditional biopsies and has many applications, including early screening, providing diagnostic cues, predicting disease severity and survival outcomes, assessing response and resistance to treatment, detecting minimal tumor burden before radiological evidence, and monitoring for disease recurrence. However, multiple challenges still need to be addressed, including reduction in variability between assays, standardization of protocols, and validation in large trials to ensure reliability. This review will focus on the latest advancements in LB applications for diagnostic and prognostic characterization of genitourinary cancers.

Background: Online adaptive radiotherapy (oART) has demonstrated improved target volume coverage and enhanced sparing of surrounding pelvic organs through daily re-optimization based on pretreatment imaging. Recently, iterative cone-beam computed tomography (iCBCT) has been integrated into oART workflows, facilitating precise daily adaptation. However, the dosimetric consequences of intra-fractional variations for clinical target volume (CTV) and organs at risk (OARs) remain insufficiently characterized.

Aim: To investigate intra-fractional CTV and OARs variation and their impact on iCBCT guided daily oART for postoperative cervical and endometrial cancer.

Methods: Seventeen patients treated with daily postoperative iCBCT guided oART with rigorous bladder and rectal preparation protocols were enrolled. CTV and OARs were contoured on pre- and post-treatment iCBCT scans. The average surface distance (ASD), dice similarity coefficient (DSC), and 95% Hausdorff distance (HD) were utilized to evaluate the difference between pre- and post-treatment structures. Dosimetric outcomes for the pretreatment target volumes and OARs were recalculated using posttreatment contours to assess the impact of intra-fractional variation.

Results: A total of 434 treatment fractions were analyzed, with an average interval time of 22 minutes between two iCBCT scans. Minimal variations were observed in the bladder, rectum, and CTV both pre- and post-treatment, with DSC exceeding 0.8. The vaginal CTV exhibited centroid deviations of 0.46 mm anteriorly, 0.11 mm laterally, and 0.58 mm superiorly, along with ASD of 1.69 mm and 95% HD of 6.42 mm. Weak correlations were observed between vaginal CTV posterior-anterior centroid deviations and rectal superior-inferior deviations (P = 0.017). Minimal dosimetric differences were observed pre- and post-treatment, with V_100% for the adapted plan of nodal CTV being 99.94% vs 99.08% and vaginal CTV being 99.97% vs 98.66%.

Conclusion: Daily iCBCT-guided oART with strict bladder and rectal preparation effectively compensates for intra-fractional variations, maintaining CTV coverage and OAR sparing across all treatment fractions.

Background: Nasopharyngeal carcinoma (NPC), exhibiting high incidence in southern China, is linked to genetic and environmental factors. Vitamin D metabolism, involving transport [group-specific component (GC) protein] and activation [25-hydroxylase (CYP2R1) enzyme], may influence NPC susceptibility and radiotherapy response. Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D [25(OH)D] levels, and are implicated in other cancers. However, their role in NPC - particularly in high-risk Han Chinese populations - and interaction with vitamin D status remains unclear. This case control study (360 NPC patients, 550 controls) investigates these relationships to inform prevention and personalized therapy.

Aim: To investigate the association between vitamin D binding protein (GC) and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.

Methods: A case control study design was adopted, and 360 patients with NPC and 550 healthy controls were included. TaqMan method was used to perform genotyping on GC gene loci rs4588, rs7041, and CYP2R1 gene loci rs10741657, rs12794714. Serum 25(OH)D levels were detected, and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.

Results: The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model [odds ratio (OR) = 1.68, 95%CI: 1.15-2.45, P = 0.007] and the recessive model (OR = 1.56, 95%CI: 1.02-2.38, P = 0.039). The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup (OR = 1.87, 95%CI: 1.11-3.15, P = 0.019) and the squamous cell carcinoma subgroup (OR = 1.89, 95%CI: 1.19-3.00, P = 0.007). The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype (P < 0.001). The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels (P = 0.003). The rs12794714 AA genotype was associated with radiotherapy resistance (OR = 1.76, 95%CI: 1.18-2.63, P = 0.005). Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.

Conclusion: GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response, and this association may be affected by serum 25(OH)D levels. This study provides a new idea for the prevention and individualized treatment in NPC.

Metabolic syndrome (MetS), characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, has been increasingly recognized as a significant contributor to the development and progression of colorectal cancer (CRC). This review comprehensively summarizes current evidence linking MetS to CRC risk and outcomes from mechanistic, epidemiological, and clinical perspectives. Mechanistic studies suggest that hyperinsulinemia, activation of the insulin-like growth factor axis, chronic systemic inflammation, and adipokine dysregulation create a tumor-promoting environment. Epidemiological data from large-scale cohort studies and meta-analyses consistently demonstrate a positive association between MetS and CRC incidence, with abdominal obesity and hyperglycemia identified as key components. Mendelian randomization studies further support a causal relationship between visceral adiposity and CRC risk. Clinically, MetS is associated with increased risk of recurrence and reduced overall and disease-free survival in CRC patients. Emerging evidence also indicates that persistent metabolic abnormalities may contribute to early-onset CRC. Interventions targeting metabolic health - including lifestyle modification and bariatric surgery - have shown potential in reducing CRC risk and improving outcomes. Despite these advances, heterogeneity in MetS definitions and a paucity of prospective interventional studies limit the generalizability of current findings. Further research is warranted to establish standardized diagnostic criteria, elucidate sex- and age-specific mechanisms, and integrate metabolic profiling into risk stratification frameworks for CRC prevention and management.

Programmed death receptor-1 inhibitors have significantly improved the prognosis of various malignancies. Nevertheless, hyperprogressive disease (HPD), recognized as a severe adverse reaction to immunotherapy, causes a substantial surge in tumor burden and notably shortens the survival of 4%-29% of patients. This article comprehensively reviews the controversies regarding the clinical definition of HPD, its cross-cancer epidemiological features (encompassing gastric cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, etc.), and potential molecular mechanisms (such as MDM2/MDM4 gene amplification, EGFR mutations, and reprogramming of the immune microenvironment). It further delves into biomarker-based predictive models, targeted combination therapy strategies, and salvage treatment alternatives. Ultimately, it puts forward future directions, including the establishment of a multicenter HPD registry database and organoid predictive models, aiming to offer evidence-based guidance for clinical practice.

Background: Intrathyroidal thymic carcinoma (ITC) is a rare malignant epithelial tumour of thymic origin occurring within the thyroid. Histologically, it resembles thymic carcinoma, with squamous cell carcinoma being the most common subtype, and immunohistochemical staining typically exhibits features consistent with thymic neoplasms.

Case summary: We report the case of a 68-year-old woman who presented with a left-sided neck mass of one year's duration. And the neck lump had been gradually enlarging over the course of a year, reaching the size of a goose egg within six months. Thyroid ultrasound revealed a normally sized thyroid gland. A 3.9 cm × 3.4 cm × 2.7 cm hypoechoic lesion with irregular echogenicity was observed outside the capsule of the lower pole of the left lobe. The mass exhibited regular morphology, well-defined margins, and close adherence to the thyroid's lower pole. Microscopic examination revealed two distinct tumour cell populations: Squamous cell carcinoma and small cell carcinoma. Immunohisto-chemical staining demonstrated divergent differentiation - one population was positive for cluster of differentiation 5 and cluster of differentiation 117, supporting thymic origin, while the other exhibited neuroendocrine differentiation with synaptophysin and chromogranin A positivity. At eight months postoperatively, the patient remained recurrence-free on chemotherapy.

Conclusion: Based on these findings, the patient was diagnosed as ITC with both squamous cell and small cell carcinoma components. To date, nearly 100 cases of ITC have been reported in the literature. However, no prior reports of ITC exhibiting both squamous cell and small cell carcinoma components. This case report provides information on the microscopic morphological features of ITC with both squamous cell and small cell carcinoma components, which can help pathologists to expands the understanding of the pathological spectrum of the disease.

Perioperative fluorouracil, leucovorin, oxaliplatin and docetaxel is currently the standard chemotherapy for resectable gastric and gastroesophageal junction adenocarcinomas, based on the results of FLOT4 and ESOPEC trials. This regimen has demonstrated efficacy in tumor downstaging, enhancing the chances of curative resection, and ultimately improving the overall survival. However, despite these advances, the complete response rate in the perioperative setting remains below 10% to 15%, highlighting the need for more effective treatment strategies. Recent studies evaluating immunotherapy, such as the KEYNOTE-585 trial with pembrolizumab and the MATTERHORN trial with durvalumab, have shown promising preliminary results, including improved response rates and event-free survival. Nevertheless, these regimens are not yet considered the standard of care. This article explores the current landscape of perioperative treatments for gastric cancer and discusses future directions in this field.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide and ranks among the top five most common malignancies. Helicobacter pylori (H. pylori) infection is recognized as the primary risk factor, although gastric carcinogenesis also reflects complex interactions among bacterial virulence factors, host genetics, and the gastric microbiome. H. pylori harbors well-characterized proteins such as CagA, VacA, BabA, and SabA that enable persistent infection and fuel tumor initiation. Recent high-quality evidence from randomized trials and meta-analyses provide strong support that H. pylori eradication therapy substantially reduces cancer risk-even in those with established precancerous lesions such as intestinal metaplasia or dysplasia. Additionally, emerging research indicate that H. pylori may influence the tumor immune microenvironment, such as through altering programmed death ligand 1 expression-which could affect immunotherapy outcomes. This review presents a cohesive and updated perspective on H. pylori-driven GC, summarizing bacterial virulence, host predispositions, microbiome interactions, epigenetic changes like DNA repair gene methylation, and evolving therapeutic implications, all while illuminating current scientific debates and emerging directions.

This article comprehensively reviews research progress in prostate cancer radiation therapy. It provides an overview of fundamental principles, encompassing the disease's epidemiology, pathological mechanisms, and radiation sensitivity, alongside technological advancements. The clinical application, technological progress, and efficacy evaluation of moderate hypofractionated radiation therapy and ultra hypofractionated radiation therapy are discussed. Diagnostic and monitoring techniques specific to radiation therapy are analyzed, alongside prevailing controversies and challenges. Finally, the review outlines future prospects, including novel radiotherapy techniques, multidisciplinary collaboration trends, and the evolving role of radiation within comprehensive treatment. The findings demonstrate continuous technological and clinical evolution in prostate cancer radiotherapy, yet emphasize the need for further exploration to optimize treatments and improve patient survival and quality of life.