Value In Malignant Tumors Research Articles

LncRNA PFAR facilitates the proliferation and migration of papillary thyroid carcinoma by competitively binding to miR-15a

Papillary thyroid carcinoma (PTC) is type of aggressive tumor, with a markedly declined survival rate when distant metastasis occurs. It is of great significance to develop potential biomarkers to evaluate the progression of PTC. LncRNAs are recently widely claimed with biomarker value in malignant tumors. Herein, the role of LncRNA PFAR in PTC was investigated to explore potential prognostic marker for PTC. Compared to NTHY-ORI 3-1 cells, LncRNA PFAR was found markedly upregulated in PTC cell lines. In LncRNA PFAR knockdown TPC-1 cells, markedly declined cell viability, increased apoptotic rate, enhancive number of migrated cells, and elevated migration distance were observed, accompanied by a suppressed activity of the RET/AKT/mTOR signaling. In LncRNA PFAR overexpressed BCPAP cells, signally increased cell viability, declined apoptotic rate, reduced number of migrated cells, decreased migration distance, and increased tumor volume and tumor weight in nude mice xenograft model were observed, accompanied by an activation of the RET/AKT/mTOR signaling. The binding site between LncRNA PFAR and miR-15a, as well as miR-15a and RET, was confirmed by the dual luciferase reporter assay. The FISH study revealed that LncRNA PFAR was mainly located in the cytoplasm. Furthermore, the impact of the siRNA targeting LncRNA PFAR against the growth and migration of PTC cells was abolished by the inhibitor of miR-15a or SC79, an activator of AKT/mTOR signaling. Collectively, LncRNA PFAR facilitated the proliferation and migration of PTC cells by mediating the miR-15a/RET axis.

CircCCDC66: Emerging roles and potential clinical values in malignant tumors.

Circular RNAs (circRNAs) are endogenous non-coding RNAs (ncRNAs) with a closed-loop structure. In recent years, circRNAs have become the focus of much research into RNA. CircCCDC66 has been identified as a novel oncogenic circRNA and is up-regulated in a variety of malignant tumors including thyroid cancer, non-small cell carcinoma, gastric cancer, colorectal cancer, renal cancer, cervical cancer, glioma, and osteosarcoma. It mediates cancer progression by regulating epigenetic modifications, variable splicing, transcription, and protein translation. The oncogenicity of circCCDC66 suppresses or promotes the expression of related genes mainly through direct or indirect pathways. This finding suggests that circCCDC66 is a biomarker for cancer diagnosis, prognosis assessment and treatment. However, there is no review on the relationship between circCCDC66 and cancers. Thus, the expression, biological functions, and regulatory mechanisms of circCCDC66 in malignant tumor and non-tumor diseases are summarized. The clinical value and prognostic significance of circCCDC66 are also evaluated, which can provide insights helpful to those exploring new strategies for the early diagnosis and targeted treatment of malignancies.

Role of ARRB1 in prognosis and immunotherapy: A Pan-Cancer analysis.

Background: β-arrestin1 (ARRB1), was originally identified as a multifunctional adaptor protein. Although ARRB1 has recently been shown to also play an important role in tumor growth, metastasis, inflammation, and immunity, its relationship with distinct tumor types and the tumor immune microenvironment remains unclear. Methods: We analyzed the ARRB1 expression profile and clinical characteristics in 33 cancer types using datasets from The Cancer Genome Atlas (TCGA) database. Clinical parameters such as patient survival, tumor stage, age, and gender were used to assess the prognostic value of ARRB1. The Human Protein Atlas (HPA) database was used to explore ARRB1 protein expression data. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration. Furthermore, putative correlations between ARRB1 and tumor-infiltrating immune cells, the signatures of T-cell subtypes, immunomodulators, the tumor mutation burden (TMB), Programmed cell death ligand 1 (PD-L1), and microsatellite instability (MSI) were also explored. Gene functional enrichment was determined using GSEA. GSE40435 and GSE13213 cohorts were used to validate the correlation of ARRB1 with KIRC and LUAD clinicopathological parameters. Finally, the relationship between ARRB1 and immunotherapeutic responses was assessed using three independent immunotherapy cohorts, namely, GSE67501, GSE168204, and IMvigor210. Results: We found that ARRB1 expression levels were lower in 17 tumor tissues than in the corresponding normal tissues. We further found that ARRB1 expression was significantly correlated with tumor stage in BRCA, ESCA, KIRC, TGCT, and THCA, while in some tumors, particularly KIRC and LUAD, ARRB1 expression was associated with better prognosis. ARRB1 expression was also positively correlated with the stromal score or the immune score in some tumors. Regarding immune cell infiltration, ARRB1 expression in DLBC was positively correlated with M1 macrophage content and negatively correlated with B-cell infiltration. Additionally, there was a broad correlation between ARRB1 expression and three classes of immunomodulators. Furthermore, high ARRB1 expression levels were significantly correlated with some tumor immune-related pathways. Finally, ARRB1 expression was significantly associated with MSI, PD-L1, and TMB in some tumors and with the efficacy of immune checkpoint inhibitors (ICIs) in melanoma. Conclusion: ARRB1 has prognostic value in malignant tumors, especially in KIRC and LUAD. At the same time, ARRB1 was closely correlated with the tumor immune microenvironment and indicators of immunotherapy efficacy, indicating its great potential as a reliable marker for predicting the efficacy of immunotherapy.

Analysis of the prognostic, diagnostic and immunological role of HSP90α in malignant tumors.

Heat shock protein 90α (HSP90α) encoded by the HSP90AA1 gene, is the stress inducible isoform of the molecular chaperone HSP90, and was demonstrated as a promising hallmark to diagnose, prognosis in malignant tumors. This study is to evaluate the value of HSP90α in diagnosis, prognosis and immunotherapy of malignant tumors by investigating the expression of HSP90α in plasma of various tumors and analyzing the expression of HSP90α at gene and protein levels via pan-cancer database. We founded that levels of HSP90α in malignant tumors groups were significantly higher than healthy controls in serum. Pan-cancer analysis showed that HSP90AA1 was highly expressed in 27 of 33 tumors, but low in individual cancers (such as renal malignancies). The plasma HSP90α level was positively correlated with the stage of malignant tumor, but there was no significant difference between HSP90AA1 and the stage of most tumors. Cox regression analysis showed that HSP90AA1 expression was significantly correlated with OS in only 6 of the 32 cancers, including LIHC, KIRC, HNSC, LUAD, BRCA and MESO. Up-regulation of HSP90AA1 in most tumors was positively correlated with PDCD1LG2 and CD274 immune checkpoint genes. T cell CD8+ was positively correlated with HSP90AA1 in COAD, DLBC and UVM, and negatively correlated with HSP90AA1 in ESCA, GBM, HNSC, KIRC, KIRP, UCEC and STAD. The AUC of HSP90α are generally high in different tumor groups, which indicated its diagnostic value in malignant tumors. In conclusion, serum HSP90α in patients with malignant tumor is generally elevated, which is of positive significance as an independent diagnosis and combined diagnosis. However, we found that the expression level of HSP90AA1 gene in most tumors was not completely consistent with the serum level, and even down-regulated in some tumors. Plasma levels can be used as biomarkers of poor prognosis in some tumors, but it cannot be used as a biomarker for poor prognosis of all tumors, and more in-depth studies are needed.

The Prognostic Value of Natural Killer Cells and Their Receptors/Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BackgroundNatural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear.MethodsSeveral electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI).Results26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57–0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57+ NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56+ NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear.ConclusionNK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.

Radiosynthesis of a novel antisense imaging probe targeting LncRNA HOTAIR in malignant glioma

BackgroundLong non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe 99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts.MethodsThe ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated 99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software.ResultsThe labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated 99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group.ConclusionThe liposome encapsulated 99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.

Biological functions and theranostic potential of HMGB family members in human cancers.

The high mobility group box (HMGB) protein family consists of four members: HMGB1, 2, 3, and 4. They share similar amino acid sequences and identical functional regions, especially HMGB1, 2, and 3. The homology in structure may lead to similarity in function. In fact, though their targets may be different, they all possess the fundamental function of binding and distorting target DNAs. However, further research confirmed they are distributed differently in tissues and involved in various distinct physiological and pathological cellular processes, including cell proliferation, division, migration, and differentiation. Recently, the roles of HMGB family members in carcinogenesis has been widely investigated; however, systematic discussion on their functions and clinical values in malignant tumors is limited. In this review, we mainly review and summarize recent advances in knowledge of HMGB family members in terms of structure, distribution, biochemical cascades, and specific mechanisms regarding tumor progression. Importantly, the diagnostic, prognostic, and therapeutic value of these proteins in cancers is discussed. Finally, we envisage the orientation and challenges of this field in further studies.

Diagnostic performance of quantitative diffusion tensor imaging for the differentiation of breast lesions at 3 T MRI

BackgroundConventional breast magnetic resonance imaging (MRI), including dynamic contrast-enhanced MR mammography, may lead to ambiguous diagnosis and unnecessary biopsies. PurposeTo investigate the contribution of quantitative diffusion tensor imaging (DTI) in the discrimination between benign and malignant breast lesions at 3 T MRI. Material and methodsThe study included a total of 86 lesions (44 benign and 42 malignant) in 58 women (34 with malignant lesions, 23 with benign lesions and 1 with both types of lesions). All patients were examined on a 3 T MRI scanner. Fractional Anisotropy (FA), Mean Diffusivity (MD), Apparent Diffusion Coefficient (ADC), as well as eigenvalues (λ1, λ2, λ3) were calculated and compared between benign and malignant lesions using two different software packages (GE Functool and ExploreDTI). ResultsMalignant lesions exhibited significantly lower ADC values compared to benign ones (ADCmal = 1.06 × 10−3 mm2/s, ADCben = 1.54 × 10−3 mm2/s, p-value < 0.0001). FA measurements in carcinomas indicated slightly higher values than those in benign lesions (FAmal = 0.20 ± 0.07, FAben = 0.15 ± 0.05, p-value = 0.0003). Eigenvalues λ1, λ2, λ3, showed significantly lower values in malignant tumors compared to benign lesions and normal breast tissue. ROC curve analysis of ADC and DTI metrics demonstrated that ADC provides high diagnostic performance (AUC = 0.944) while, MD and λ1 showed best discriminative results (AUC = 0.906) for the differentiation of malignant and benign lesions in contrast to other DTI parameters. ConclusionThe addition of eigenvalue analysis improves DTI's ability to differentiate between benign and malignant breast lesions.

Using lesion washout volume fraction as a biomarker to improve suspicious breast lesion characterization.

The purpose of this study was to evaluate using lesion washout (WO) volume fraction as a biomarker to improve the characterization of suspicious breast lesions. Study lesions consisted of a total of 60 malignant tumors (BI‐RADS 6) and 62 suspicious lesions (BI‐RADS 4 or 5). The biopsies of these suspicious lesions resulted in a total of 30 malignant tumors and 32 benign lesions, respectively, yielding a 48.4% positive predictive value (PPV) of the biopsies. The mean and standard deviation of the lesion WO volume fraction of these 60 BI‐RADS 6 malignant tumors were first computed to establish a 99% sensitivity threshold value for malignant tumors, and then the biomarker was used to characterize the suspicious lesions. Using the biomarker would characterize all the malignant tumors as malignant, 12 out of the 32 benign lesions as benign, potentially resulting in a 24% improvement rate in the PPV of the biopsies (from 48.4% to 60%) and consequently a 22.5% reduction rate in the false‐positive rate of benign biopsies (from 51.6% to 40%). The lesion WO volume fraction biomarker could improve the computer‐based assessment of breast MRI by increasing the PPV of breast biopsies and reducing the number of unnecessary biopsies without compromising sensitivity.PACS number: 87.61.Tg, 87.19.Xj

A Comparative Study of F-18 FDG PET and 201Tl Scintigraphy for Detection of Primary Malignant Bone and Soft-Tissue Tumors

The purpose of this study was to compare 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) and Tl-201 chloride (Tl) scintigraphy for detection of primary malignant bone and soft-tissue tumors. A total of 40 patients with suspicion of malignant bone and soft-tissue tumors were examined. FDG PET imaging was performed at 1-hour post-FDG injection. Tl planar and single photon emission computed tomography images were acquired 10 minutes (early) and 2 hours (delayed) after injection of Tl. We evaluated FDG and Tl uptake visually and semiquantitatively using standardized uptake value and tumor to contralateral normal tissue ratio on planar images, respectively. Of the 33 patients with malignant tumors, all but 2 liposarcomas showed positive accumulation on FDG PET. However, all 7 benign lesions were also positive on FDG PET. Both early and delayed Tl images were positive for 27 of the 33 malignant tumors. Of the 6 false-negative cases on Tl images, 5 were liposarcomas. Both early and delayed Tl images were negative for 5 of the 7 benign lesions. The sensitivity of FDG PET for detection of primary malignant bone and soft-tissue tumors was 94% and the specificity, 0%. The corresponding values for Tl scintigraphy were 82% and 71%. The mean FDG standardized uptake value in malignant tumors was higher than that in benign lesions, but this difference was not statistically significant. Statistically significant differences were observed between malignant and benign lesions for both early and delayed tumor to contralateral normal tissue ratios. FDG PET was found to be more sensitive than Tl scintigraphy for primary malignant bone and soft-tissue tumors, although it was less specific.

Lymph Node Metastases in Malignant Tumors of the Paranasal Sinuses

To assess the frequency of nodal involvement and its prognostic value in malignant tumors of the paranasal sinuses, particularly in maxillary sinus squamous cell carcinoma. Retrospective review. Tertiary cancer center. The medical records of 704 consecutive patients surgically treated for malignant tumors of the paranasal sinuses from January 1968 to March 2003 were reviewed. The tumors were staged according to American Joint Committee on Cancer-International Union Against Cancer 2002 classification. Only patients with clinically positive nodes underwent a neck dissection. Lymph node metastases (at presentation or during follow-up, occurring alone, or with concurrent local recurrence and/or distant metastasis). Also analyzed were local recurrence (occurring alone or with concurrent distant metastasis), distant metastasis (occurring alone), and overall survival. The tumor site was the ethmoid sinus in 305 cases and maxillary sinus in 399 cases. At baseline, 5 patients (1.6%) in the ethmoid sinus group and 33 (8.3%) in the maxillary sinus group presented with positive nodes (P < .001); during follow-up, nodal recurrences (alone or simultaneous with T and/or M recurrence) occurred in 15 and 51 patients, respectively, and the corresponding 5-year incidence estimates were 4.3% and 12.5% (P = .001). The highest incidence of node metastases was found in maxillary sinus squamous cell carcinoma, particularly in T2 tumors. Five-year overall survival estimates were 45.3% for patients with N0 tumors and 0% for those with N+ (N1, N2, or N3) ethmoid sinus tumors, and 50.6% and 16.8%, respectively, for patients with maxillary sinus tumors. Lymph node metastases are a poor prognostic factor for patients with malignant tumors of the paranasal sinuses. The incidence of these metastases is low, particularly in ethmoid sinus tumors. A prophylactic treatment of the neck in patients with N0 tumors (surgery or radiotherapy) might be considered in T2 squamous cell carcinoma of the maxillary sinus and in undifferentiated carcinoma of the ethmoid sinus.

Is 0.6T magnetic resonance mammography adequate in the detection of breast cancer?

To evaluate whether relevant diagnostic information can be achieved when using magnetic resonance mammography (MRM) on mid-field as a supplement to conventional imaging and clinical examination in women with primary breast cancer. 30 women (55 breasts containing 49 malignant tumors) planned for uni- or bilateral mastectomy were examined with dynamic MRM on mid-field, 0.6T. The women were examined with mammography (M) and ultrasonography (US) prior to MRM. The descriptions of the conventional examinations were evaluated retrospectively, whereas the MRM was evaluated prospectively, with knowledge of the M+US findings. Imaging findings suggesting malignancy were registered and correlated with pathology after mastectomy. A home-made rating system for evaluation of the detected lesions was tested. MRM detected seven additional malignant tumors, failed to detect three lesions and characterized four as gray-zone lesions according to the rating system. Sensitivity of finding the tumors with M+US was 79.0%, with a PPV for malignant tumors of 84.4%. One breast in which MRM found a malignant tumor had not initially been examined with US. Sensitivity with MRM was 91.6%, with a positive predictive value of malignant tumors of 97.7%. MRM on mid-field seems to improve the detection of cancers when used as a supplement to M+US in women with primary breast cancer. We believe that the results are fair compared to MRM on high-field, although further research and refinement are needed.

Morphological changes of the nucleolar organizer regions induced by 7,12-dimethylbenz[a]anthracene in the hamster cheek pouch.

The staining of nucleolar organizer regions (NORs), which equate to rDNA transcription, was applied to chemically induced-lesions of the hamster cheek pouch. The cheek pouches of 16 male golden Syrian hamsters were treated three times a week with 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil for 16 weeks. The percentage of gathered-type NORs with high activity nucleoli increased in the pouch epithelium during DMBA treatment and reached the highest values in malignant tumors. The percentage of dispersed-type NORs also increased in the malignant lesions. However, the absolute number of NORs was not affected by DMBA treatment. These results suggest that DMBA induces modification of NOR activity at the early stages of carcinogenesis and shows the potential of this model for studying NOR alterations in neoplasia.