DNA Methylation-Based Testing in Liquid Biopsies as Detection and Prognostic Biomarkers for the Four Major Cancer Types

Cells, Год журнала: 2020, Номер 9(3), С. 624 - 624

Опубликована: Март 5, 2020

Lung, breast, colorectal, and prostate cancers are the most incident worldwide. Optimal population-based cancer screening methods remain an unmet need, since detection at early stages increases prospects of successful curative treatment, leading to a lower incidence recurrences. Moreover, current parameters for patients’ stratification have been associated with divergent outcomes. Therefore, new biomarkers that could aid in prognosis, preferably detected by minimally invasive major importance. Aberrant DNA methylation is event development may be circulating cell-free (ccfDNA), constituting valuable biomarker. Furthermore, stable alteration can easily rapidly quantified methylation-specific PCR methods. Thus, main goal this review provide overview important studies report prognosis four after critical analysis available literature. methylation-based show promise management, some describing “PanCancer” approach simultaneous several types. Nonetheless, still lack large-scale validation, precluding implementation clinical practice.

Язык: Английский

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Circ-ZKSCAN1 regulates FAM83A expression and inactivates MAPK signaling by targeting miR-330-5p to promote non-small cell lung cancer progression

Translational Lung Cancer Research, Год журнала: 2019, Номер 8(6), С. 862 - 875

Опубликована: Дек. 1, 2019

Circular RNAs (circRNAs) belong to a new type of endogenous non-coding RNA and plays key role in carcinogenesis. Circ-ZKSCAN1 (hsa_circ_0001727) has been proven be tumor-dependent circRNA. However, its non-small cell lung cancer (NSCLC) underreported.The expression patterns circ-ZKSCAN1 were determined using qRT-PCR NSCLC samples lines. Cell proliferation was examined utilizing the CCK-8 assay. migration invasion evaluated Transwell The combination miR-330-5p cells analyzed by pull-down luciferase reporter We used bioinformatics software circbank, CircInteractome, TargetScan Miranda predict circRNA-miRNA miRNA-mRNA interactions.Our results showed that significantly up-regulated NSCLC, closely related malignant characteristics poor prognosis, clinically tumor size clinical stage. Subsequent experiments could inhibit growth vitro vivo. Importantly, can act as sponge carcinogenic increase FAM83A, resulting inhibition MAPK signal transduction pathway, thus promoting progress NSCLC. Interestingly, FAM83A caused overexpression turn promote circ-ZKSCAN1.Circ-ZKSCAN1 is positive regulator clarifies potential molecular mechanism circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop

Язык: Английский

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Prognostic implications of cellular senescence in resected non-small cell lung cancer

Translational Lung Cancer Research, Год журнала: 2022, Номер 11(8), С. 1526 - 1539

Опубликована: Авг. 1, 2022

Background: Cure and long-term survival for non-small cell lung cancer (NSCLC) remains hard to achieve. Cellular senescence, an emerging hallmark of cancer, is considered as endogenous tumor suppressor mechanism. However, senescent cells can paradoxically affect the surrounding microenvironment (TME), ultimately leading relapse metastasis. As such, role cellular senescence in highly controversial. Methods: In 155 formalin-fixed paraffin-embedded (FFPE) samples from surgically resected NSCLC patients with pathological tumor-node-metastasis (pTNM) stages I–IV (8th edition), was assessed using a combination four immunohistochemical markers, i.e., lipofuscin, p16INK4a, p21WAF1/Cip1 Ki67, correlated clinicopathological parameters outcomes, including overall (OS) disease-free (DFS). Results: A tumoral signature (SS) present 48 out patients, but did not correlate any parameter, except p53 mutation status. histologically homogenous patient cohort 100 who fulfilled following criteria: (I) one type histology, adenocarcinoma, (II) without known epidermal growth factor receptor (EGFR) mutation, (III) curative (R0) resection (IV) no neoadjuvant systemic therapy or radiotherapy, median OS DFS SS (n=30, 30.0%) compared (n=70, 70.0%) 53 versus 141 months (P=0.005) 45 55 (P=0.25), respectively. multiple Cox proportional hazards (Cox PH) model analysis correcting age, pTNM stage I–III adjuvant therapy, remained significant prognostic (HR =2.03; P=0.014). Conclusions: The presence particularly based on high p16INK4a expression significantly affects adenocarcinoma. this light, senolytic could be interesting strategy harboring SS, improve these patients.

Язык: Английский

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PLCG2 can exist in eccDNA and contribute to the metastasis of non-small cell lung cancer by regulating mitochondrial respiration

Cell Death and Disease, Год журнала: 2023, Номер 14(4)

Опубликована: Апрель 8, 2023

Abstract Extrachromosomal circular DNAs (eccDNAs) participate in tumorigenesis and tumor progression. However, the role mechanism of eccDNAs have yet to be elucidated non-small cell lung cancer (NSCLC). In our research, three surgically matched NSCLC tissue samples, lines (H1299, A549, H460), a normal line (MRC-5) were used as study objects. High-throughput eccDNA sequencing bioinformatics analysis performed distribution pattern level expression. The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT‒PCR western blotting experiments verify expression PLCG2. Our results showed that chromosome distribution, length genomic annotation comparable between groups. Nevertheless, there no significant differences tissues tissues. derived from cells. TCGA immunohistochemistry highly expressed tended associated with poor outcome. We also demonstrated can promote metastasis through regulation mitochondrial respiration. These suggested identified acts an oncogene might new biomarker for diagnosis prognosis evaluation.

Язык: Английский

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Survival After Mediastinal Node Dissection, Systematic Sampling, or Neither for Early Stage NSCLC

Journal of Thoracic Oncology, Год журнала: 2020, Номер 15(10), С. 1670 - 1681

Опубликована: Июнь 21, 2020

IntroductionThe American College of Surgeons Oncology Group Z0030 found no survival difference between patients with early stage NSCLC who had mediastinal nodal dissection or systematic sampling. However, a meta-analysis 1980 in five randomized controlled trials from 1989 to 2007 associated better dissection. We tested the impact extent curative-intent resections for population-based observational cohort.MethodsResections clinical T1 T2, N0 nonhilar N1, M0 four contiguous United States Hospital Referral Regions 2009 2019 were categorized into dissection, sampling, and "neither" on basis evaluation lymph node stations. compared demographic characteristics, perioperative complication rates, after assessing statistical interactions confounding.ResultsOf 1942 eligible patients, 18% 6% 75% an intraoperative that met neither standard. In teaching hospitals, was lower hazard death than (0.57 [95% confidence interval: 0.41–0.79]) but not sampling (0.74 [0.40–1.37]) adjusting multiple comparisons. There significant ratios at nonteaching institutions (p > 0.3 all comparisons). Perioperative rates significantly worse "neither," 0.1 comparisons).ConclusionsIn institutions, superior over less-comprehensive pathologic staging. finding warrants further investigation.

Язык: Английский

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Assessment of an Exhaled Breath Test Using High-Pressure Photon Ionization Time-of-Flight Mass Spectrometry to Detect Lung Cancer

JAMA Network Open, Год журнала: 2021, Номер 4(3), С. e213486 - e213486

Опубликована: Март 30, 2021

Importance

Exhaled breath is an attractive option for cancer detection. A sensitive and reliable test has the potential to greatly facilitate diagnoses therapeutic monitoring of lung cancer.

Objective

To investigate whether able detect using highly high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS).

Design, Setting, Participants

This diagnostic study was conducted with a prospective-specimen collection, retrospective-blinded evaluation design. samples were collected before surgery detected by HPPI-TOFMS. The detection model constructed support vector machine (SVM) algorithm. Patients pathologically confirmed recruited from Peking University People's Hospital, healthy adults without pulmonary noncalcified nodules Aerospace 731 Hospital. Data analysis performed August October 2020.

Exposures

Breath testing SVM

Main Outcomes Measures

performance measured sensitivity, specificity, accuracy, area under receiver-operating characteristic curve (AUC).

Results

139 patients 289 adults, all tested. Of participants, 228 (53.27%) women mean (SD) age 57.0 (11.4) years. After clinical outcomes ascertained, participants randomly assigned into discovery data set (381 participants) blinded validation (47 participants). further broken training (286 (95 construct model. reached 92.97% (4.64%) 96.68% (2.21%) 95.51% (1.93%) accuracy in after 500 iterations. In participants), revealed sensitivity 100%, specificity 92.86%, 95.74%, AUC 0.9586.

Conclusions Relevance

study's results suggest that HPPI-TOFMS feasible accurate detection, which may be useful future screenings.

Язык: Английский

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Normal Tissue Complication Probability Modeling of Pulmonary Toxicity After Stereotactic and Hypofractionated Radiation Therapy for Central Lung Tumors

International Journal of Radiation Oncology*Biology*Physics, Год журнала: 2017, Номер 100(3), С. 738 - 747

Опубликована: Ноя. 22, 2017

Язык: Английский

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Dysregulated expression and functions of microRNA-330 in cancers: A potential therapeutic target

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 146, С. 112600 - 112600

Опубликована: Дек. 27, 2021

As small non-coding RNAs, MicroRNAs (miRNAs) bind to the 3' untranslated region (3'-UTR) of mRNA targets control gene transcription and translation. The miR-330 has two miRNA products, including miR-330-3p miR-330-5p, which exhibit anti-tumorigenesis and/or pro-tumorigenesis effects in many kinds malignancies. In cancers, miR-330-5p aberrant expression can influence malignancy-related processes such as cell proliferation, migration, invasion, apoptosis epithelial-mesenchymal transition, well angiogenesis responsiveness treatment. cancer types (such lung, prostate, gastric, breast, bladder, ovarian, colorectal, pancreatic cancer, osteosarcoma), acts an anti-tumor agent. These cancers have low levels that leads upregulation tumor promotor target genes leading progression. Here, overexpression using inducers prevent development. Dual roles been also indicated thyroid, liver cervical cancers. Moreover, exhibits lung osteosarcoma, bladder cancer. downregulation inhibitors Demonstrated breast dual roles. Importantly, activities are regulated by upstream regulators long RNAs (lncRNAs), circular linear lncRNAs. This review comprehensively explained role development while highlighting their downstream possible therapeutic strategies.

Язык: Английский

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Effect of Adjuvant Chemotherapy on Survival of Patients With 8th Edition Stage IB Non-Small Cell Lung Cancer

Frontiers in Oncology, Год журнала: 2022, Номер 11

Опубликована: Янв. 27, 2022

Background The efficacy of adjuvant chemotherapy in patients with 8th edition stage IB (tumor size ≤4 cm) non-small cell lung cancer (NSCLC) remains unclear. Methods We identified 9757 eligible (non-chemotherapy group: n=8303; n=1454) between 2004 and 2016 from the Surveillance, Epidemiology End Results (SEER) database. Log-rank test was used to compare overall survival (OS) non-chemotherapy groups. Cox regression model applied investigate independent prognosis factors all surgically treated patients, then nomogram constructed. Propensity score matching (PSM) performed reduce confounding bias, subgroup analyses matched cohort were also performed. Finally, we reviewed 184 NSCLC July 2008 December Jinling Hospital as a validation cohort, compared disease-free (DFS) OS two In SEER database associated improved both unmatched (1417 pairs) cohorts (all P <0.05). benefit (both DFS) confirmed (P Multivariate analysis showed age, race, sex, marital status, histology, tumor location, size, differentiation, surgical method, lymph nodes (LNs) examined, radiotherapy prognostic for resected concordance index calibration curves demonstrated good prediction effect. Subgroup following characteristics benefited chemotherapy: old poor differentiation undifferentiation, 0-15 LNs visceral pleural invasion (VPI), lobectomy no Conclusions Adjuvant is especially those poorly differentiated undifferentiated tumors, VPI, lobotomy radiotherapy. Further prospective trials are needed confirm these conclusions. Besides, provides relatively accurate patients.

Язык: Английский

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Diagnostic and Prognostic Value of hsa_piR_022710, hsa_piR_019822, and hsa_piR_020840 in Early-Stage Non-Small-Cell Lung Cancer: Implications for Recurrence and Survival in Squamous Cell Carcinoma Patients

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2870 - 2870

Опубликована: Март 21, 2025

Despite significant advancements in early detection and treatment, non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. Specifically, early-stage cases, recurrence after surgery continues to be the principal death for these patients. The urgent need novel diagnostic prognostic biomarkers has directed attention towards PIWI-interacting RNAs (piRNAs), group small that regulate genomic stability epigenetics. Some piRNAs, including hsa_piR_022710, hsa_piR_019822, hsa_piR_020840, have been described as deregulated various cancers. This study investigated expression three piRNAs by RT-qPCR 277 NSCLC patients developed survival CART classification models predict risk, overall (OS), disease-free (DFS). hsa_piR_019822 hsa_piR_020840 were able discriminate between tumor normal tissue, well adenocarcinoma squamous cell carcinoma (LUSC) Elevated hsa_piR_022710 was correlated with an increased risk poorer DFS OS LUSC Patients high more greatly benefited from adjuvant treatment. In summary, higher piRNA levels associated outcomes, especially patients, where they may help guide personalized treatment strategies.

Язык: Английский

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