Cisplatin-based chemotherapy is a standard treatment for lung adenocarcinoma (LUAD), yet acquired cisplatin resistance remains a marked cause of treatment failure. The molecular mechanisms driving cisplatin resistance in LUAD have not been fully elucidated. The present study integrated bulk transcriptomic data, genomic mutation profiles and single-cell RNA sequencing data to systematically investigate cisplatin resistance in LUAD. Resistance-associated genes were identified through differential expression, survival analysis and database integration. Unsupervised clustering was used to define cisplatin resistance-associated subtypes. Functional characteristics were explored using pathway enrichment, immune infiltration, tumor mutation burden and weighted gene co-expression network analysis. A machine learning framework incorporating 101 algorithms was applied to identify key genes and construct a prognostic model. Single-cell analyses and in vitro experiments were performed to validate the biological role of the core gene. Molecular docking and molecular dynamics simulations were conducted to identify potential therapeutic compounds. A total of two molecular subtypes with distinct cisplatin resistance levels and prognostic outcomes were identified. The high-resistance subtype exhibited enhanced cell cycle activity, DNA repair signaling and immune heterogeneity. Machine learning analysis revealed a five-gene signature, with chaperonin-containing TCP1 subunit 2 (CCT2) emerging as a key regulator of cisplatin resistance. Single-cell analyses showed that CCT2 was predominantly enriched in resistant epithelial cell subpopulations. Functional experiments demonstrated that CCT2 knockdown significantly inhibited cell proliferation and enhanced cisplatin sensitivity in LUAD cell lines. A number of candidate compounds targeting CCT2 exhibited stable binding in silico. The present findings identified CCT2 as a key mediator of cisplatin resistance in LUAD and provided potential therapeutic strategies to overcome chemotherapy resistance.
Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, as the majority of patients are diagnosed at an advanced disease stage. CA19-9, the biomarker most commonly used in clinical practice, lacks adequate sensitivity and specificity for early PDAC detection. Increasing evidence indicates that alterations in gut, oral and tumor-associated microbiota are associated with PDAC development and progression, supporting the potential diagnostic value of microbiome-based biomarkers in this disease. Multiple diagnostic models have been developed for PDAC using fecal, salivary or tissue-derived microbial profiles, and the combination of microbial signatures with CA19-9 or metabolomic markers has improved diagnostic performance in a number of cohorts. Despite these advancements, the clinical translation of microbiome-based models remains limited by methodological heterogeneity, patient-related variability, low levels of microbial biomass in pancreatic tissue and a lack of large-scale prospective validation. In addition, the majority of available evidence for microbiota-based alterations in PDAC is derived from retrospective case-control studies, and the reported diagnostic performance should therefore be interpreted cautiously. The present review summarizes current evidence on PDAC-associated microbial alterations and microbiome-based diagnostic models, and discusses the methodological, biological and regulatory challenges that must be addressed before microbiota-based approaches can be integrated into routine clinical practice.
In order to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with anti-angiogenic agents and chemotherapy regimens as first-line treatment for gene-negative advanced lung adenocarcinoma, a retrospective analysis was performed on the clinical data of patients with driver gene-negative advanced lung adenocarcinoma who received the ICI-Based Triple Combination regimen at The Sixth Affiliated Hospital (School of Medicine, South China University of Technology, Foshan, China) between January 2022 and December 2024. Among the enrolled patients, the objective response rate was 58.3%, and the disease control rate was 83.3%. The median progression-free survival was 25.4 months [95% confidence interval (CI): 12.7-38.0 months], and the median overall survival was 26.6 months (95% CI: 21.3-31.8 months). The most common treatment-related adverse events were hematological toxicity (58.3%), followed by nausea and vomiting (50.0%), fatigue and anorexia (33.3%), muscle pain (33.3%) and chest tightness with shortness of breath (33.3%). All symptoms improved after symptomatic treatment. The present study showed that the ICI-based triple combination regimen exhibited promising antitumor activity and a manageable safety profile in patients with driver gene-negative advanced lung adenocarcinoma.
Cutaneous angiosarcoma is a rare and aggressive malignant vascular tumor that most commonly affects the scalp and face of elderly individuals. Because its early clinical manifestations are often non-specific, it may be misdiagnosed as a benign inflammatory or infectious disorder, resulting in delayed diagnosis and treatment. The case of a 95-year-old Asian man is reported, who presented with a 5-month history of a progressively enlarging scalp lesion that had initially been diagnosed as cellulitis and treated with antibiotics without improvement. Physical examination revealed a 4×5 cm ill-defined violaceous infiltrative plaque with central ulceration on the scalp. Histopathological examination demonstrated irregular anastomosing vascular channels lined by mildly atypical endothelial cells infiltrating the dermis and subcutis. Immunohistochemical staining was positive for CD31, CD34 and erythroblast transformation-specific related gene, with a Ki-67 index of ~20%; C-MYC staining showed weak focal positivity in ~10% of the lesional cells, whereas cytokeratin and epithelial membrane antigen staining were negative. Additional immunohistochemical staining demonstrated negative human herpesvirus 8 staining and the absence of a continuous smooth muscle actin-positive pericytic layer around the neoplastic vascular channels. Imaging studies showed no evidence of regional or distant metastasis. The patient subsequently underwent wide local excision with a 2 cm gross peripheral margin to the level of the galea aponeurotica. Intraoperative frozen-section and final permanent-section examinations confirmed tumor-free surgical margins. Adjuvant radiotherapy was not administered because of the advanced age of the patient and complete excision with negative margins. At the 8-month postoperative follow-up, clinical examination showed no evidence of local recurrence. The present case highlights that primary cutaneous angiosarcoma of the scalp may closely mimic cellulitis in its early stage, particularly in elderly patients, and that a progressive violaceous scalp lesion unresponsive to conventional antibiotic therapy should prompt early biopsy and histopathological evaluation.
Acute radiation enteritis (ARE) is a common complication of pelvic radiotherapy in patients with cervical cancer and may adversely affect treatment tolerance and nutritional status. The present retrospective study investigated whether the pre-radiotherapy modified prognostic nutritional index (mPNI), a cholesterol-modified nutritional and immune-related score, is associated with ARE in patients with cervical cancer receiving radiotherapy. A total of 92 patients with pathologically confirmed cervical cancer who completed radiotherapy at Fuyang People's Hospital Affiliated to Anhui Medical University (Fuyang, China) between January 2023 and December 2025 were included. ARE was graded according to the Radiation Therapy Oncology Group acute lower gastrointestinal toxicity criteria, with grade ≥1 ARE defined as the primary endpoint. Sensitivity analyses were conducted using grade ≥2 and grade ≥3 ARE as more clinically relevant endpoints. mPNI was calculated from pre-radiotherapy total cholesterol level, albumin level and total lymphocyte count. During radiotherapy, 67 patients developed grade ≥1 ARE. Pre-radiotherapy mPNI was higher in the ARE group than in the non-ARE group [median, 88.27 (interquartile range, 81.26-97.02) vs. 76.41 (interquartile range, 70.22-80.38); P<0.001]. In the clinically adjusted logistic regression model, a higher mPNI remained significantly associated with grade ≥1 ARE [odds ratio (OR), 1.163; 95% confidence interval (CI), 1.072-1.261; P<0.001]. Sensitivity analyses likewise demonstrated significant associations between mPNI and grade ≥2 ARE (OR, 1.069; 95% CI, 1.023-1.117; P=0.003) and grade ≥3 ARE (OR, 1.071; 95% CI, 1.013-1.133; P=0.016). Receiver operating characteristic curve analysis showed good discriminatory performance for grade ≥1 ARE, with an area under the curve of 0.835 (95% CI, 0.732-0.917), an optimal cut-off value of 80.406, a sensitivity of 79.1% and a specificity of 76.0%. These findings suggest that pre-radiotherapy mPNI may serve as a practical laboratory-based indicator for identifying patients with cervical cancer at increased risk of developing ARE during radiotherapy.
