Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

SUMMARYTumor evolution is a key feature of tumorigenesis and plays a pivotal role in driving intratumor heterogeneity, treatment failure and patients’ prognosis. Here we performed single-cell transcriptome profiling of 46 primary liver cancers from 37 patients enrolled for interventional studies. We surveyed the landscape of ~57,000 malignant and non-malignant cells and determined tumor cell clonality by developing a machine learning-based consensus clustering method. We found evidence of tumor cell branching evolution using hierarchical clustering, RNA velocity as well as reverse graph embedding methods. Interestingly, an increasing tumor cell clonality was tightly linked to patients’ prognosis, accompanied by a polarized immune cell landscape. We identified osteopontin as a key player for tumor cell evolution and microenvironmental reprogramming. Our study offers insight into the collective behavior of tumor cell communities in liver cancer as well as potential drivers for tumor evolution in response to therapy.

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Expression of β-Catenin in Hepatocellular Carcinoma

Revista de Chimie ◽

10.37358/rc.20.3.7979 ◽

2001 ◽

Vol 71 (3) ◽

pp. 116-125

Author(s):

Norina Basa ◽

Daniela Lazar ◽

Remus Cornea ◽

Sorina Taban ◽

Melania Ardelean ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Tumor Cell ◽

Mitotic Index ◽

Histological Grade ◽

Proliferation Index ◽

Tumor Cell Proliferation ◽

Ki 67 ◽

B Virus ◽

Development And Evolution

Alteration of β-catenin expression is involved in the development and evolution of hepatocellular carcinoma (HCC); β-catenin is able to influence tumor cell proliferation. We analyzed the immunohistochemical (IHC) expression of β-catenin on a group of 32 patients diagnosed with HCC using the anti-β-catenin monoclonal antibody (clone E247). We correlated the expression of β-catenin with the proliferation index of Ki-67 (PI Ki-67), the mitotic index (MI) and other clinical and pathological features. We observed an altered β-catenin expression in 58.38% of all HCC cases. This expression was insignificantly correlated with tumor size (]5 cm) (p = 0.683), histological grade G1-G2 (p = 0.307), vascular invasion (p = 0.299) and advanced pT stage (p = 0.453); we obtained a significantly higher MI in HCC with altered β-catenin expression (p = 0.018), as compared to HCC without overexpression (1.66 � 1.37) (p = 0.038) and a PI Ki-67 of 22.49 � 20.1 and 28.24 � 18.2, respectively in tumors with altered β-catenin expression with insignificant differences compared to HCC without overexpression (25.95 � 15.2) (p = 0.682 and p = 0.731, respectively). According to the results we obtained, aberrant β-catenin expression in HCC was correlated with a high mitotic index, therefore playing an important role in tumor progression by stimulating tumor cell proliferation; non-nuclear β-catenin overexpression can have a pathological significance in HCC, especially in cases of HCC associated with hepatitis B virus (HBV) infection.

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Differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma using contrast-enhanced ultrasound: A systematic review and meta-analysis

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211145 ◽

2021 ◽

pp. 1-17

Author(s):

Yanling Chen ◽

Wenping Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Diagnostic Accuracy ◽

Publication Bias ◽

Likelihood Ratio ◽

Intrahepatic Cholangiocarcinoma ◽

Cochrane Library ◽

Arterial Phase ◽

Contrast Enhanced Ultrasound ◽

Diagnostic Ability ◽

Contrast Enhanced

AIM: To explore the diagnostic ability of contrast-enhanced ultrasound (CEUS) in distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for studies reporting the diagnostic accuracy of CEUS in differentiating ICC from HCC. The diagnostic ability of CEUS was assessed based on the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) with 95% confidence intervals (CIs). The methodologic quality was assessed by the QUADAS-2 tool. Subgroup analyses, meta-regression and investigation of publication bias were performed to identify the source of heterogeneity. RESULTS: A total of eight studies were included, consisting of 1,116 patients with HCC and 529 with ICC. The general diagnostic performance of CEUS in distinguishing ICC and HCC were as follows: pooled sensitivity, 0.92 (95% CI: 0.84–0.96); pooled specificity, 0.87 (95% CI: 0.79–0.92); pooled PLR, 7.1 (95% CI: 4.1–12.0); pooled NLR, 0.09 (95% CI: 0.05–0.19); pooled DOR, 76 (95% CI: 26–220) and AUC, 0.95(95% CI: 0.93–0.97). Different liver background may be a potential factor that influenced the diagnostic accuracy of CEUS according to the subgroup analysis, with the pooled DOR of 89.67 in the mixed liver background group and 46.87 in the cirrhosis group, respectively. Six informative CEUS features that may help differentiate HCC from ICC were extracted. The three CEUS features favoring HCC were arterial phase hyperenhancement(APHE), mild washout and late washout (>60s); the three CEUS favoring ICC were arterial rim enhancement, marked washout and early washout(<60s). No potential publication bias was observed. CONCLUSION: CEUS showed great diagnostic ability in differentiating ICC from HCC, which may be promising for noninvasive evaluation of these diseases.

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Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

Nature Communications ◽

10.1038/s41467-021-25240-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Vidya C. Sinha ◽

Amanda L. Rinkenbaugh ◽

Mingchu Xu ◽

Xinhui Zhou ◽

Xiaomei Zhang ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Mouse Model ◽

Transition State ◽

Tumor Cell ◽

Single Cell ◽

Tumor Cells ◽

Breast Lesions ◽

Aggressive Tumor ◽

Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

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