Maosen Xu

Background: Portal vein tumor thrombus (PVTT) marks advanced hepatocellular carcinoma (HCC) and carries a dismal prognosis. Survival varies widely even within this stage, yet simple tools for individualized risk stratification remain scarce. Methods: We retrospectively enrolled 134 HCC patients with PVTT and randomly divided them into a training set (n = 94) and a validation set (n = 40). Clinical predictors were selected by variance inflation factor screening and backward elimination Cox regression. A radiomics score (Rad-score) was constructed from portal-venous phase computed tomography (CT) images using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression with 10-fold cross-validation. Three Cox models were built: a clinical model, an imaging model based solely on the Rad-score, and a combined model integrating both. Discrimination was assessed by C-index and time-dependent area under the curve (AUC). Calibration was examined with bootstrap-based calibration curves. Decision curve analysis evaluated net benefit. A nomogram was developed from the combined model. Results: Four clinical variables (alpha-fetoprotein (AFP), body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), and alkaline phosphatase (ALP)) and two CT texture features (GLRLM_SRHGE and GLZLM_SZHGE) were retained as independent predictors. The combined model gave the highest C-index in both the training set (0.843) and the internal validation set (0.815). Its 1-year AUC reached 0.953 and 0.947 in the two sets. Calibration slopes ranged from 1.044 to 1.291 across time points, indicating a tendency toward mild overdispersion; nevertheless, decision curve analysis confirmed net benefit across clinically relevant thresholds. The combined model offered greater net benefit than either single-domain model across a 0–50% threshold range. A nomogram incorporating all five predictors was generated for individualized 12- and 24-month survival prediction. Conclusions: A combined model integrating routine laboratory variables and a CT-based radiomics score improved survival prediction over clinical or imaging models alone. The corresponding nomogram uses inputs from a basic blood panel and a single portal-venous phase CT, suggesting its potential as a low-cost prognostic stratification tool for HCC patients with PVTT, although external validation in prospective multicenter cohorts is required before clinical implementation.

Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part of the tumor microenvironment, the tumor stroma is highly dynamic, heterogeneous and commonly tumor-type specific, and it mainly includes noncellular compositions such as the extracellular matrix and the unique cancer-associated vascular system as well as a wide variety of cellular components including activated cancer-associated fibroblasts, mesenchymal stromal cells, pericytes. All these elements operate with each other in a coordinated fashion and collectively promote cancer initiation, progression, metastasis and therapeutic resistance. Over the past few decades, numerous studies have been conducted to study the interaction and crosstalk between stromal components and neoplastic cells. Meanwhile, we have also witnessed an exponential increase in the investigation and recognition of the critical roles of tumor stroma in solid tumors. A series of clinical trials targeting the tumor stroma have been launched continually. In this review, we introduce and discuss current advances in the understanding of various stromal elements and their roles in cancers. We also elaborate on potential novel approaches for tumor-stroma-based therapeutic targeting, with the aim to promote the leap from bench to bedside.

The chemokine ligand CCL2 and its receptor CCR2 are implicated in the initiation and progression of various cancers. CCL2 can activate tumour cell growth and proliferation through a variety of mechanisms. By interacting with CCR2, CCL2 promotes cancer cell migration and recruits immunosuppressive cells to the tumour microenvironment, favouring cancer development. Over the last several decades, a series of studies have been conducted to explore the CCL2‐CCR2 signalling axis function in malignancies. Therapeutic strategies targeting the CCL2‐ CCR2 axis have also shown promising effects, enriching our approaches for fighting against cancer. In this review, we summarize the role of the CCL2‐CCR2 signalling axis in tumorigenesis and highlight recent studies on CCL2‐CCR2 targeted therapy, focusing on preclinical studies and clinical trials.