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15 pages, 940 KiB

Open AccessArticle

A Highly Sensitive XNA-Based RT-qPCR Assay for the Identification of ALK, RET, and ROS1 Fusions in Lung Cancer

by Bongyong Lee, Andrew Chern, Andrew Y. Fu, Aiguo Zhang and Michael Y. Sha

Diagnostics 2024, 14(5), 488; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics14050488 - 24 Feb 2024

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Abstract

Lung cancer is often triggered by genetic alterations that result in the expression of oncogenic tyrosine kinases. Specifically, ALK, RET, and ROS1 chimeric receptor tyrosine kinases are observed in approximately 5–7%, 1–2%, and 1–2% of NSCLC patients, respectively. The presence of these fusion [...] Read more.

Lung cancer is often triggered by genetic alterations that result in the expression of oncogenic tyrosine kinases. Specifically, ALK, RET, and ROS1 chimeric receptor tyrosine kinases are observed in approximately 5–7%, 1–2%, and 1–2% of NSCLC patients, respectively. The presence of these fusion genes determines the response to tyrosine kinase inhibitors. Thus, accurate detection of these gene fusions is essential in cancer research and precision oncology. To address this need, we have developed a multiplexed RT-qPCR assay using xeno nucleic acid (XNA) molecular clamping technology to detect lung cancer fusions. This assay can quantitatively detect thirteen ALK, seven ROS1, and seven RET gene fusions in FFPE samples. The sensitivity of the assay was established at a limit of detection of 50 copies of the synthetic template. Our assay has successfully identified all fusion transcripts using 50 ng of RNA from both reference FFPE samples and cell lines. After validation, a total of 77 lung cancer patient FFPE samples were tested, demonstrating the effectiveness of the XNA-based fusion gene assay with clinical samples. Importantly, this assay is adaptable to highly degraded RNA samples with low input amounts. Future steps involve expanding the testing to include a broader range of clinical samples as well as cell-free RNAs to further validate its applicability and reliability. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

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11 pages, 3571 KiB

Open AccessArticle

Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung

by Min Hye Kim, Jeong Hee Lee, Jong Sil Lee, Dong Chul Kim, Jung Wook Yang, Hyo Jung An, Ji Min Na, Wook Jae Jung and Dae Hyun Song

Diagnostics 2023, 13(22), 3475; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13223475 - 19 Nov 2023

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Abstract

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one [...] Read more.

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one of the most prominent metabolic changes observed in cancers. Therefore, the PLIN protein family has recently attracted attention owing to its role in lipid metabolism and cancer. To date, no studies have addressed the association between the prognosis of lung cancer and PLIN1 expression. For the first time, we found that high PLIN1 expression was significantly correlated with worse disease-free survival (DFS) in lung squamous cell carcinoma (SCC). We examined PLIN1 expression by the immunohistochemical analysis of surgical lung SCC specimens obtained from 94 patients. We analyzed the correlation between PLIN1 expression, clinicopathological data, and patient survival, using a chi-squared test, Kaplan–Meier analysis with log-rank tests, and the multivariate Cox proportional hazards regression test. High PLIN1 expression was significantly correlated with lower DFS in the Kaplan–Meier analysis and the multivariate Cox proportional hazards regression model. High PLIN1 expression was significantly correlated with worse prognosis in lung SCC. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

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12 pages, 254 KiB

Open AccessArticle

Analytical Performance and Concordance with Next-Generation Sequencing of a Rapid, Multiplexed dPCR Panel for the Detection of DNA and RNA Biomarkers in Non-Small-Cell Lung Cancer

by Kerri Cabrera, Jeffrey Gole, Bryan Leatham, Matthew J. Springer, Molly Smith, Leah Herdt, Lucien Jacky and Bradley A. Brown

Diagnostics 2023, 13(21), 3299; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13213299 - 25 Oct 2023

Cited by 2 | Viewed by 1663

Abstract

FDA approval of targeted therapies for lung cancer has significantly improved patient survival rates. Despite these improvements, barriers to timely access to biomarker information, such as nucleic acid input, still exist. Here, we report the analytical performance and concordance with next-generation sequencing (NGS) [...] Read more.

FDA approval of targeted therapies for lung cancer has significantly improved patient survival rates. Despite these improvements, barriers to timely access to biomarker information, such as nucleic acid input, still exist. Here, we report the analytical performance and concordance with next-generation sequencing (NGS) of a highly multiplexed research-use-only (RUO) panel using digital PCR (dPCR). The panel’s analytical sensitivity and reactivity were determined using contrived DNA and RNA mixes. The limit of blank was established by testing FFPE curls classified as negative by pathology. Concordance was established on 77 FFPE samples previously characterized using the Oncomine Precision Assay^®, and any discordant results were resolved with Archer Fusionplex^® and Variantplex^® panels. The analytical sensitivity, reported as the estimated mutant allele fraction (MAF), for DNA targets ranged from 0.1 to 0.9%. For RNA targets (ALK, RET, ROS, NTRK 1/2/3 Fusions, and MET Exon 14 skipping alteration), the analytical sensitivity ranged from 23 to 101 detected counts with 5 ng of total RNA input. The population prevalence-based coverage ranged from 89.2% to 100.0% across targets and exceeded 99.0% in aggregate. The assay demonstrated >97% concordance with respect to the comparator method. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

11 pages, 1685 KiB

Open AccessArticle

A Nomogram Based on Consolidation Tumor Ratio Combined with Solid or Micropapillary Patterns for Postoperative Recurrence in Pathological Stage IA Lung Adenocarcinoma

by Longfu Zhang, Jie Liu, Dawei Yang, Zheng Ni, Xinyuan Lu, Yalan Liu, Zilong Liu, Hao Wang, Mingxiang Feng and Yong Zhang

Diagnostics 2023, 13(14), 2376; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13142376 - 14 Jul 2023

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Abstract

Background: Patients with pathological stage IA lung adenocarcinoma (LUAD) are at risk of relapse. The value of the TNM staging system is limited in predicting recurrence. Our study aimed to develop a precise recurrence prediction model for stage IA LUAD. Materials and methods: [...] Read more.

Background: Patients with pathological stage IA lung adenocarcinoma (LUAD) are at risk of relapse. The value of the TNM staging system is limited in predicting recurrence. Our study aimed to develop a precise recurrence prediction model for stage IA LUAD. Materials and methods: Patients with pathological stage IA LUAD who received surgical treatment at Zhongshan Hospital Fudan University were retrospectively analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for recurrence-free survival (RFS). The predictive performance of the model was assessed using calibration plots and the concordance index (C-index). Results: The multivariate Cox regression analysis revealed that CTR (0.75 < CTR ≤ 1; HR = 9.882, 95% CI: 2.036–47.959, p = 0.004) and solid/micropapillary-predominance (SMPP; >5% and the most dominant) (HR = 4.743, 95% CI: 1.506–14.933, p = 0.008) were independent prognostic factors of RFS. These risk factors were used to construct a nomogram to predict postoperative recurrence in these patients. The C-index of the nomogram for predicting RFS was higher than that of the eighth T-stage system (0.873 for the nomogram and 0.643 for the eighth T stage). The nomogram also achieved good predictive performance for RFS with a well-fitted calibration curve. Conclusions: We developed and validated a nomogram based on CTR and SMP patterns for predicting postoperative recurrence in pathological stage IA LUAD. This model is simple to operate and has better predictive performance than the eighth T stage system, making it suitable for selecting further adjuvant treatment and follow-up. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

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12 pages, 999 KiB

Open AccessArticle

The Impact of Liquid Biopsies Positive for EGFR Mutations on Overall Survival in Non-Small Cell Lung Cancer Patients

by Jonnathan Roldan Ruiz, Marta Gracia Fuentes Gago, Luis Miguel Chinchilla Tabora, Idalia Gonzalez Morais, José María Sayagués, Mar Abad Hernández, Maria Rosa Cordovilla Pérez, Maria Dolores Ludeña de la Cruz, Edel del Barco Morillo and Marta Rodriguez Gonzalez

Diagnostics 2023, 13(14), 2347; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13142347 - 12 Jul 2023

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Abstract

In recent years, non-small cell lung cancer treatment has been revolutionized. EGFR tyrosine kinase inhibitors and our improved understanding of its alterations have driven new diagnostic strategies. Liquid biopsies have emerged as a useful tool in these contexts, showing potential utility in early [...] Read more.

In recent years, non-small cell lung cancer treatment has been revolutionized. EGFR tyrosine kinase inhibitors and our improved understanding of its alterations have driven new diagnostic strategies. Liquid biopsies have emerged as a useful tool in these contexts, showing potential utility in early diagnosis combined with low-dose CT scans, as well as potential in monitoring treatment response and predicting the development of patients. We studied the circulating tumor DNA (ctDNA) of 38 EGFR-mutated non-small cell lung cancer patients at diagnosis in different moments of their disease by liquid biopsy techniques. Our results show that mean overall survival was significantly lower when a liquid biopsy was positive for the detection of EGFR mutations compared with wild-type patients in their liquid biopsy in both univariate (29 ± 4 vs. 104 ± 19 months; p = 0.004) and multivariate analysis (p = 0.008). Taking this into consideration, liquid biopsies could be key to improving the control of this disease. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

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14 pages, 2998 KiB

Open AccessArticle

Indications and Limits of Surgery for Spinal Metastases Derived from Lung Cancer: A Single-Center Experience

by Silvia Terzi, Federica Trentin, Cristiana Griffoni, Elisa Carretta, Stefano Bandiera, Cristina Ferrari, Fabio Vita, Alberto Righi, Margherita Maioli, Dario De Biase, Annalisa Monetta, Giovanni Barbanti Brodano, Gisberto Evangelisti, Marco Girolami, Valerio Pipola, Marco Gambarotti and Alessandro Gasbarrini

Diagnostics 2023, 13(12), 2093; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13122093 - 16 Jun 2023

Viewed by 1090

Abstract

Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung [...] Read more.

Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung cancer spinal metastases and identify any factors related to a better survival rate. We recruited 56 consecutive patients (34 male and 22 female) surgically treated for metastatic lung cancer in the spine from 2009 to 2019. Surgical indications were based on a previously published and validated flow chart following a multidisciplinary evaluation. We assessed the localization of vertebral metastases, the presence of other bone or visceral metastases, neurological status according to the Frankel score, ambulatory autonomy, and general status, measured with the Karnofsky performance scale. The expected prognosis was retrospectively assessed according to the revised Tokuhashi score. The median survival was 8.1 months, with over a third of patients surviving more than 1 year. We observed a global improvement in all clinical parameters after surgical treatment. The Tokuhashi predictive score did not correlate with survival after surgery. The results of this study suggest that the surgical treatment of symptomatic spinal metastases from lung cancer can improve quality of life, even in patients with a shorter life expectancy, by controlling pain and improving autonomy. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

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17 pages, 7997 KiB

Open AccessArticle

Identification of New Prognostic Genes and Construction of a Prognostic Model for Lung Adenocarcinoma

by Xueping Chen, Liqun Yu, Honglei Zhang and Hua Jin

Diagnostics 2023, 13(11), 1914; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13111914 - 30 May 2023

Cited by 1 | Viewed by 1297

Abstract

Lung adenocarcinoma (LUAD) is a rapidly progressive malignancy, and its mortality rate is very high. In this study, we aimed at finding novel prognosis-related genes and constructing a credible prognostic model to improve the prediction for LUAD patients. Differential gene expression, mutant subtype, [...] Read more.

Lung adenocarcinoma (LUAD) is a rapidly progressive malignancy, and its mortality rate is very high. In this study, we aimed at finding novel prognosis-related genes and constructing a credible prognostic model to improve the prediction for LUAD patients. Differential gene expression, mutant subtype, and univariate Cox regression analyses were conducted with the dataset from the Cancer Genome Atlas (TCGA) database to screen for prognostic features. These features were employed in the following multivariate Cox regression analysis and the produced prognostic model included the stage and expression of SMCO2, SATB2, HAVCR1, GRIA1, and GALNT4, as well as mutation subtypes of TP53. The exactness of the model was confirmed by an overall survival (OS) analysis and disease-free survival (DFS) analysis, which indicated that patients in the high-risk group had a poorer prognosis compared to those in the low-risk group. The area under the receiver operating characteristic curve (AUC) was 0.793 in the training group and 0.779 in the testing group. The AUC of tumor recurrence was 0.778 in the training group and 0.815 in the testing group. In addition, the number of deceased patients increased as the risk scores raised. Furthermore, the knockdown of prognostic gene HAVCR1 suppressed the proliferation of A549 cells, which supports our prognostic model that the high expression of HAVCR1 predicts poor prognosis. Our work created a reliable prognostic risk score model for LUAD and provided potential prognostic biomarkers. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

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Review

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18 pages, 4688 KiB

Open AccessReview

The Value of Micro-CT in the Diagnosis of Lung Carcinoma: A Radio-Histopathological Perspective

by Serpil Dizbay Sak, Selim Sevim, Arda Buyuksungur, Ayten Kayı Cangır and Kaan Orhan

Diagnostics 2023, 13(20), 3262; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13203262 - 20 Oct 2023

Cited by 1 | Viewed by 1308

Abstract

Micro-computed tomography (micro-CT) is a relatively new imaging modality and the three-dimensional (3D) images obtained via micro-CT allow researchers to collect both quantitative and qualitative information on various types of samples. Micro-CT could potentially be used to examine human diseases and several studies [...] Read more.

Micro-computed tomography (micro-CT) is a relatively new imaging modality and the three-dimensional (3D) images obtained via micro-CT allow researchers to collect both quantitative and qualitative information on various types of samples. Micro-CT could potentially be used to examine human diseases and several studies have been published on this topic in the last decade. In this study, the potential uses of micro-CT in understanding and evaluating lung carcinoma and the relevant studies conducted on lung and other tumors are summarized. Currently, the resolution of benchtop laboratory micro-CT units has not reached the levels that can be obtained with light microscopy, and it is not possible to detect the histopathological features (e.g., tumor type, adenocarcinoma pattern, spread through air spaces) required for lung cancer management. However, its ability to provide 3D images in any plane of section, without disturbing the integrity of the specimen, suggests that it can be used as an auxiliary technique, especially in surgical margin examination, the evaluation of tumor invasion in the entire specimen, and calculation of primary and metastatic tumor volume. Along with future developments in micro-CT technology, it can be expected that the image resolution will gradually improve, the examination time will decrease, and the relevant software will be more user friendly. As a result of these developments, micro-CT may enter pathology laboratories as an auxiliary method in the pathological evaluation of lung tumors. However, the safety, performance, and cost effectiveness of micro-CT in the areas of possible clinical application should be investigated. If micro-CT passes all these tests, it may lead to the convergence of radiology and pathology applications performed independently in separate units today, and the birth of a new type of diagnostician who has equal knowledge of the histological and radiological features of tumors. Full article

(This article belongs to the Special Issue Diagnosis and Management of Lung Cancer)

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