Tumor necrosis as a poor prognostic predictor on postoperative survival of patients with solitary small hepatocellular carcinoma

Ling, Yihong; Chen, Jie-wei; Wen, Sijian; Huang, Chaoyun; Li, Peng; Lu, Lianghe; Mei, Jie; Li, Shaohua; Wei, Wei; Cai, Mengli; Guo, Rong

doi:10.1186/s12885-020-07097-5

Cited by 49 publications

(47 citation statements)

References 37 publications

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“…Our results showed that patients with high MD/TD were more likely to show MVI. HCC patients with vascular invasion have a poor prognosis [24], and our study con rmed that patients with high MD/TD were more likely to relapse compared with patients with low MD/TD (P<0.001). Wang et al reported that circulating tumor DNA correlates with MVI and predicts tumor recurrence of HCC [17].…”

Section: Discussionsupporting

confidence: 64%

TP53 Mutation in Circulating exoDNA Correlates with Outcomes of Patients with Hepatocellular Carcinoma.

Lei

et al. 2020

Preprint

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Background: Detection of tumor-specific mutations in exosomal DNA (exoDNA), a promising liquid biopsy material, has been used to assess the prognosis of hepatocellular carcinoma (HCC) patients. This study was the first to use a droplet digital PCR (ddPCR) platform to detect tumor-specific mutations in circulating exoDNA and to evaluate the prognosis of HCC patients.Methods: Blood samples from 40 HCC patients were obtained between 2018 and 2019, with clinically annotated follow-up until 2020. A ddPCR platform was used to detect an HCC tumor-specific mutation in the TP53 gene. We analyzed the correlation between TP53 mutation detected in circulating exoDNA and patient clinical data. The ratio of mutant droplets/total droplets (MD/TD) was calculated according to ddPCR results.Results: TP53 mutations in circulating exoDNA were detected in 33 of the 40 patients (82.5%). Patients with high MD/TD (>62.5%) were more likely to show microvascular invasion (P=0.028) and high MD/TD predicted a shorter recurrence-free survival time (P<0.001).Conclusions: High MD/TD of TP53 detected in serum was associated with microvascular invasion and might be used to predict the prognosis of HCC patients. The diagnostic performance of detecting exosome-derived tumor DNA will likely improve when more mutations in other tumor-specific genes are combined.

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Section: Discussionsupporting

confidence: 64%

TP53 Mutation in Circulating exoDNA Correlates with Outcomes of Patients with Hepatocellular Carcinoma.

Lei

et al. 2020

Preprint

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“…Tumor necrosis is an important hallmark of aggressive cancers and associated with poorer patient prognosis in different types of cancer ( 51 – 54 ). By using tumor spheroids, which mimic the 3D architecture of a tumor in vitro , we looked for the abundance of the central necrotic core with or without MB expression under both normoxia and 1% hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties

et al. 2021

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Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor architecture and physiology with a heterogeneous cell population of proliferating cells in the rim and non-cycling or necrotic cells in the core region. This central necrosis was increased after MB knockdown, indicating a role for MB in hypoxic tumor regions. In addition, MB knockdown caused higher levels of HIF-1α protein after treatment with NO, which also plays an important role in cancer cell survival. MB knockdown also led to higher reactive oxygen species (ROS) levels in the cells after treatment with H2O2. To further explore the role of MB in cell survival, we performed RNA-Seq after MB knockdown and NO treatment. 1029 differentially expressed genes (DEGs), including 45 potential HIF-1 target genes, were annotated in regulatory pathways that modulate cellular function and maintenance, cell death and survival, and carbohydrate metabolism. Of these target genes, TMEFF1, TREX2, GLUT-1, MKNK-1, and RAB8B were significantly altered. Consistently, a decreased expression of GLUT-1, MKNK-1, and RAB8B after MB knockdown was confirmed by qPCR. All three genes of interest are often up regulated in cancer and correlate with a poor clinical outcome. Thus, our data indicate that myoglobin might influence the survival of breast cancer cells, possibly due to its ROS and NO scavenging properties and could be a valuable target for cancer therapy.

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“…For the tumor necrosis criteria, we considered a cutoff point ≤10% for classifying tumor as high or low in necrotic areas. After a complete assessment of the tumor bed, tumor necrosis areas with a histopathologic appearance of homogenous clusters of dead cells or cells organized into groups forming a coagulum containing cytoplasmic and nuclear debris, we quantified them as described in previous studies on other types of cancer [ 20 ] and classified them into one of the groups defined in our study.…”

Section: Methodsmentioning

confidence: 99%

“…However, histopathological investigation can provide much more valuable information regarding tumor cell architecture, stromal component, local immune response, and the presence of necrosis that might carry additional prognostic potential. These histopathological features have proven their predictive value in different types of cancers and are currently used in clinical practice [ 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Histological Features in Squamous Cell Carcinoma Involving Head and Neck Skin and Mucosa

Căruntu

Moraru

Lupu

et al. 2021

JCM

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Background: squamous cell carcinoma (SCC) is the second most common type of malignancy worldwide. Skin and mucosa of the head and neck areas are the most frequently affected. An aggressive behavior in SCC is not easily detected, and despite all efforts, mortality in these types of cancer did not show major improvements during recent decades. In this study, we aim to determine the role of histological features available through standard pathology assessment in SCC and their relation with tumor behavior and patients’ survival. Method: in a group of one hundred patients diagnosed with SCC involving the head and neck areas, we assessed the presence of four histological features (tumor/stroma ratio, immune infiltration at the front of invasion, tumor-budding activity, and tumor necrosis), their correlations with tumor type (mucosal or cutaneous), tumor clinicopathological characteristics, and their prognostic potential. Results: the comparison between histological features in cutaneous versus mucosal SCC reveals no significant differences for any of the four parameters assessed. We found significant correlations between tumor/stroma ratio and lymphatic metastasis (p = 0.0275), perineural invasion (p = 0.0006), and clinical staging (p = 0.0116). Immune infiltration at the front of invasion revealed similar correlations with lymph node involvement (p = 0.002), perineural invasion (p = 0.0138), and clinical staging (p = 0.0043). Tumor budding and tumor necrosis correlated with the size of the tumor (p = 0.0077 and p = 0.0004) and the clinical staging (p = 0.0039 and p = 0.0143). In addition, tumor budding was significantly correlated with perineural invasion (p = 0.0454). In mucosal SCC, patients with improved outcome revealed high values for the tumor/stroma ratio (p = 0.0159) and immune infiltration at the front of invasion (p = 0.0274). However, the multivariate analysis did not confirm their independent prognostic roles. Conclusions: extended histological assessments that include features such as tumor/stroma ratio, immune infiltration at the front of invasion, tumor budding, and tumor necrosis can be an easy, accessible method to collect additional information on tumor aggressiveness in skin and mucosa SCC affecting the head and neck areas.

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Tumor necrosis as a poor prognostic predictor on postoperative survival of patients with solitary small hepatocellular carcinoma

Cited by 49 publications

References 37 publications

TP53 Mutation in Circulating exoDNA Correlates with Outcomes of Patients with Hepatocellular Carcinoma.

TP53 Mutation in Circulating exoDNA Correlates with Outcomes of Patients with Hepatocellular Carcinoma.

Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties

Assessment of Histological Features in Squamous Cell Carcinoma Involving Head and Neck Skin and Mucosa

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