Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCA^phl) and peripheral small duct type (iCCA^pps). S100P + SPP1− iCCA^phlhas significantly reduced levels of infiltrating CD4⁺T cells, CD56⁺NK cells, and increased CCL18⁺macrophages and PD1⁺CD8⁺T cells compared to S100P-SPP1 + iCCA^pps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCA^ppshas significantly more SPP1⁺macrophage infiltration, less aggressiveness and better survival than S100P + SPP1− iCCA^phl. Moreover, S100P-SPP1 + iCCA^ppsharbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA.

Radiomics is an emerging field in oncological research. In this study, we aimed at developing a radiomics score (rad-score) to estimate postoperative recurrence and survival in patients with solitary hepatocellular carcinoma (HCC). A total of 319 solitary HCC patients (training cohort: n = 212; validation cohort: n = 107) were enrolled. Radiomics features were extracted from the artery phase of preoperatively acquired computed tomography (CT) in all patients. A rad-score was generated by using the least absolute shrinkage and selection operator (lasso) logistic model. Kaplan-Meier and Cox’s hazard regression analyses were used to evaluate the prognostic significance of the rad-score. Final nomograms predicting recurrence and survival of solitary HCC patients were established based on the rad-score and clinicopathological factors. C-index and calibration statistics were used to assess the performance of nomograms. Six potential radiomics features were selected out of 110 texture features to formulate the rad-score. Low rad-score positively correlated with aggressive tumor phenotypes, like larger tumor size and vascular invasion. Meanwhile, low rad-score was significantly associated with increased recurrence and reduced survival. In addition, multivariate analysis identified the rad-score as an independent prognostic factor (recurrence: Hazard ratio (HR): 2.472, 95% confident interval (CI): 1.339–4.564, p = 0.004;survival: HR: 1.558, 95%CI: 1.022–2.375, p = 0.039). Notably, the nomogram integrating rad-score had a better prognostic performance as compared with traditional staging systems. These results were further confirmed in the validation cohort. The preoperative CT image based rad-score was an independent prognostic factor for the postoperative outcome of solitary HCC patients. This score may be complementary to the current staging system and help to stratify individualized treatments for solitary HCC patients.

Background: Small hepatocellular carcinoma (SHCC) is a special type of hepatocellular carcinoma with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. However, the prognostic factors for SHCC remain controversial. The purpose of this study is to clarify the predictive factors of SHCC. Methods: The study population consisted of 458 patients underwent hepatectomy for single SHCC between January 2006 and December 2008. Clinical data (included age, gender, virus infection, serum alfa-fetoprotein level, cirrhosis, capsule, border), histopathologic features (included differentiation, morphology subtype, microvascular invasion, tumor infiltrative lymphocytes (TIL), inflammatory injury grade and fibrosis stage of surrounding liver), were evaluated to identify prognostic factors influencing SHCC patients’ survival and microvascular invasion. Results: There were 384 males (83.8%) and 74 (16.2%) females with median ages of 52 years. The median progression-free survival (PFS) and overall survival (OS) durations were 53 and 54 months, respectively. About 91.9% (n = 421) SHCC were infected by Hepatitis B. One hundred forty-seven of the 446 (33.0%) patients with pre-operation serum AFP level record had serum alfa-fetoprotein (AFP) level ≥ 200 ug/ml and 178 of the 280 (63.8%) patients with post-operation serum AFP level record had AFP level ≥ 20 ug/ml. Liver cirrhosis was present in 411 cases (89.7%), while 434 (97.3%) tumors had clear border, and 250 (55.6%) tumors were encapsulated. MVI was identified in 83 patients (18.1%). In univariate analysis, a significant association between the presence of MVI and shortened PFS and OS was found (p = 0.012, 0.028, respectively). Histological differentiation had strong relationship with MVI (p = 0.009), in terms of MVI was more easily presented in patients with worse histological differentiation. In patients with MVI, worse survival was correlated with female patients, patients with G2 or G3 histological differentiation, pre-operation serum AFP level ≥ 200 ug/ml or post-operation serum AFP level ≥ 20 ug/ml, and TIL ≥ 50/HPF. Conclusions: MVI is an independent poorer prognostic factor for PFS and OS of single SHCC patients. Tumor histological differentiation was closely related with MVI.

The synergistic effect of neoadjuvant immunotherapy and chemoradiotherapy in gastric adenocarcinoma is unclear. This phase II trial (NCT03631615) investigated this neoadjuvant combination in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Thirty-six patients received capecitabine 850 mg/m² twice daily and simultaneous radiotherapy for 5 weeks, sandwiched by a 21-day cycle of oxaliplatin 130 mg/m² (day 1) plus capecitabine 1000 mg/m² twice daily (days 1–14), respectively, followed by surgery. Camrelizumab 200 mg (day 1) was given for 5 cycles since initiating chemotherapy. Primary endpoint was pathological complete response (pCR, ypT0) rate. Secondary endpoints included total pCR (tpCR, ypT0N0) rate, major pathological response (MPR, < 10% residual tumor cells) rate, margin-free (R0) resection rate, downstaging, progression-free survival (PFS), overall survival (OS), and safety. The pCR rate was 33.3% (95% CI, 18.6–51.0), meeting pre-specified endpoint. TpCR, MPR, and R0 resection rates were 33.3%, 44.4%, and 91.7%, respectively. Twenty-eight (77.8%) patients reached ypN0. Two-year PFS and OS rates were 66.9% and 76.1%, respectively. The most common grade 3–4 adverse event was decreased lymphocyte count (27 [75.0%]). Neoadjuvant camrelizumab plus concurrent chemoradiotherapy exhibits promising pathological response in patients with locally advanced gastric adenocarcinoma, with an acceptable safety profile.