Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/.

Understanding of dedifferentiation, an indicator of poo prognosis for patients with thyroid cancer, has been hampered by imprecise and incomplete characterization of its heterogeneity and its attributes. Using single-cell RNA sequencing, we explored the landscape of thyroid cancer at single-cell resolution with 46,205 cells and delineated its dedifferentiation process and suppressive immune microenvironment. The developmental trajectory indicated that anaplastic thyroid cancer (ATC) cells were derived from a small subset of papillary thyroid cancer (PTC) cells. Moreover, a potential functional role of CREB3L1 on ATC development was revealed by integrated analyses of copy number alteration and transcriptional regulatory network. Multiple genes in differentiation-related pathways (e.g., EMT) were involved as the downstream targets of CREB3L1, increased expression of which can thus predict higher relapse risk of PTC. Collectively, our study provided insights into the heterogeneity and molecular evolution of thyroid cancer and highlighted the potential driver role of CREB3L1 in its dedifferentiation process.

Circulating tumor cells (CTCs), which have stem cell-like characteristics, might play a crucial role in cancer metastasis. CD44 has been identified as gastric cancer (GC) stem cell (CSC) marker. Here, the prognostic significance of CD44-positive CTCs in GC patients was investigated. CTCs were detected in 27 of 45 GC patients. The presence of CTCs was significantly associated with lymph node metastasis, distant metastasis, and recurrence (P = 0.007, P = 0.035, and P = 0.035, resp.). Nineteen of the 27 CTC-positive patients had CD44-positive CTCs. These patients were more likely to develop metastasis and recurrence than patients with CD44-negative CTCs. CD44-positive CTC counts were higher in recurrent patients than in the nonrecurrent ones (means 4.8 and 1.9, resp.; P = 0.010). Furthermore, 13 of 19 patients with CD44-positive CTCs developed recurrent disease, and the mean time to recurrence was shorter than that in patients with CD44-negative CTCs (10.54 ± 5.55 and 19.13 ± 9.72 months, resp.; P = 0.04). COX proportional hazards model indicated that the presence of CD44-positive CTCs and TNM stage were independent predictors of recurrence for GC (P = 0.030 and 0.008). So identifying the stem cell-like CTC subset may provide more clinically useful prognostic information than only detecting CTCs.

KEY WORDS: non-small cell lung cancer; anaplastic lymphoma kinase (ALK); Ventana immunohistochemistry (IHC) assay; fluorescence; fluorescence in situ hybridization (FISH); malignant pleural effusion; cell block.

In this study, we systematically explored the clinical manifestations, diagnosis, treatment, and prognosis of renal epithelioid angiomyolipoma (EAML) retrospectively by analyzing data of 52 patients diagnosed with EAML at four centers. Our results showed that the onset of EAML was usually inconspicuous, and so no obvious symptoms or signs had occurred in most patients at diagnosis. Its diagnoses always depended on postoperative pathological examination. The immunohistochemical (IHC) results [HMB45 ( + ), cytokeratin (-), and S100 (-)] could be used to differentiate EAML from other malignancies such as renal cell cancer (RCC) and sarcomas. For treatment, surgery resulted in satisfactory short-term prognosis. The long-term prognosis of patients with EAML was poor, particularly when a large size, a high percentage of epithelioid component, tumor thrombus formation, and necrosis were present. In conclusion, EAML is a tumor with malignant potential. Once diagnosed, integrated approaches, including surgery, chemotherapy, and targeted therapy, should be considered; a close follow-up regimen is necessary for cases that met: 1) tumor size >9 cm, 2) tumor thrombus formation in the vein, 3) epithelioid cells >70% or atypia cells >60%, and 4) necrosis.