Genetic Testing and Molecular Biomarkers

Journal Information
ISSN / EISSN: 19450265 / 19450257
Total articles ≅ 1,945

Latest articles in this journal

, Kimberly Mae C. Ong, Angeli Carlos-Hiceta, Ma. Leah C. Tantoco, Talitha Karisse L. Yarza, Ma. Luz San Agustin, Melquiadesa Pedro, Teresa Luisa G. Cruz, Eva Maria Cutiongco-De la Paz, Generoso T. Abes, et al.
Published: 1 January 2023
Genetic Testing and Molecular Biomarkers, Volume 27, pp 12-17; https://doi.org/10.1089/gtmb.2022.0171

Abstract:
Background: Many indigenous peoples are at elevated risk for otitis media, however there is limited information on hearing loss due to OM in these communities. An Indigenous Filipino community that has previously been described with an elevated prevalence of OM that is due to rare A2ML1 variants and a common FUT2 variant underwent additional phenological testing. In this study, we describe the audiologic profiles in A2ML1- and FUT2-related otitis media and the validity of otoscopy and genotyping for A2ML1 and FUT2 variants in screening for otitis media and hearing loss. Method: We analyzed A2ML1 and FUT2 genotypes together with demographic, otologic and audiologic data from tympanometry and hearing level assessments of 109 indigenous individuals. Results: We confirmed previous findings of a spectrum of nonsyndromic otitis media as associated with A2ML1 variants. A2ML1 and FUT2 variants were associated with high-frequency hearing loss at 4000 Hz. As expected, young age was associated with flat tympanograms, and eardrum perforations due to chronic otitis media were associated with severe-to-profound hearing loss across frequencies. Adding A2ML1 or FUT2 genotypes improved the validity of otoscopy as a screening test to rule out moderate-to-profound hearing loss. Conclusion: Continued multi-disciplinary management and audiologic follow-up using tympanometry and screening audiometry are needed to document and treat otitis media and prevent permanent hearing loss in the indigenous community.
, Puja Shah, Anne Weidner, Ann Tezak, Lindsay Venton, Brenda Zuniga, Sonya Reid, Deborah Cragun
Published: 1 January 2023
Genetic Testing and Molecular Biomarkers, Volume 27, pp 1-4; https://doi.org/10.1089/gtmb.2022.0160

Abstract:
Purpose: Scalable solutions are needed to make pre-test genetic education about inherited cancer risk accessible across diverse and underserved populations. We evaluated an automated strategy to deliver genetic education through a web-based video among young Black females with breast cancer. Methods: 96 participants were recruited through state cancer registries in Florida and Tennesee. All participants viewed a 12 min video and completed a ten question quiz on inherited cancer knowledge before and after viewing the video. Median pre- and postvideo knowledge scores were categorized as <60% versus ≥60% and compared across demographic and clinical characteristics using binary logistic regression. Results: Of the 96 participants, mean age was 51, over 50% had income <$50 K, over 40% did not graduate college or have private insurance, and over 70% had previous genetic testing. Median knowledge scores significantly increased after viewing the video (p < 001), with no significant differences in those with or without prior testing. A higher post-video knowledge score was associated with an income ≥$50 K, a college degree, and private insurance (all p < .05). Conclusion: Among a population of young Black breast cancer patients, the educational video significantly increased knowledge. Findings support the use of automated pre-test educational tools as a scalable solution to make these services more accessible across populations.
Zhiju Liu, Hua Jiang, Rongchang Zhao, Qiuying Quan, Xiaohong Huang
Published: 1 January 2023
Genetic Testing and Molecular Biomarkers, Volume 27, pp 18-26; https://doi.org/10.1089/gtmb.2022.0173

Abstract:
Background: Long non-coding RNAs (lncRNAs), as functional components of the human genome, are widely involved in cell proliferation, differentiation, apoptosis, migration and invasion by several types of cancer, including lung cancer. However, the role of lncRNA IPW in lung cancer has not been fully elucidated. The aim of the present study was to characterize the expression and clinical significance of lncRNA IPW in lung cancer. Materials and Methods: IPW expression in tumor samples and cells was assessed using the Oncomine and Cancer Cell Line Encyclopedia (CCLE) database, respectively. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine IPW expression and microRNA-370 (miR-370) expression. The clinical significance of IPW was evaluated by Chi-square test and Kaplan-Meier pot analyses. In addition, the sulforhodamine blue (SRB) assays was used to detect cell proliferation in IPW-overexpressed A549 cells. Results: IPW expression was significantly down-regulated in NSCLC tissues and was significantly associated with many clinicopathological data, including smoking history, differentiation, pT factor, pN factor and pTNM stage (p < 0.05). Decreased IPW expression was correlated with poor survival (p = 1.5e-05) and was positively associated with first progression in patients with lung adenocarcinoma (p = 0.00041). Furthermore, IPW could inhibit A549 cell proliferation and expression of miR-370. High miR-370 expression was associated with poor overall survival (OS) among lung adenocarcinoma patients (p = 0.045). Conclusions: These findings provide evidence that down-regulation of IPW might be considered as a beneficial prognostic biomarker and that it could potentially serve as therapeutic target in lung adenocarcinoma.
YaQiong Tian, Zhijuan Fan, Shuang Liu, Yujing Wu, Shuye Liu
Published: 1 January 2023
Genetic Testing and Molecular Biomarkers, Volume 27, pp 5-11; https://doi.org/10.1089/gtmb.2022.0141

Abstract:
Aims: Mitochondrial functional transformation contributes to the carcinogenesis of the prostate by meeting the metabolic needs of cancer cells. Mitochondrial transcription factor A (TFAM) is a pivotal regulator that maintains homeostasis of mitochondrial function. However, its role in prostate carcinogenesis has not been well elucidated. Materials and Methods: In the present study, we analyzed the expression of TFAM in normal prostate tissue and prostate cancer using public databases; a prostate-tissue chip was used to verify the results. The expression of TFAM in normal cells and in prostate cancer cells was determined by western blotting analysis. We knocked down TFAM in the prostate cancer cell line PC3 using a specific shRNA to explore the potential effects of TFAM in prostatic carcinogenesis. Results: We observed higher expression levels of TFAM in prostate cancer tissue than in normal prostate tissue and tumor adjacent normal tissues. A receiver operating characteristic curve was drawn that demonstrated the diagnostic efficacy of using TFAM expression for prostate cancer prognoses. Elevated levels of TFAM may indicate poorer overall survival in prostate cancer patients. Western blotting assays also showed that relative to the normal prostatic epithelial cell line RWPE-1, prostate cancer cell lines PC3 and DU145 expressed more TFAM protein. Furthermore, knockdown of TFAM inhibited the colony-formation capability of PC3 cells. Conclusion: Collectively, these results suggest that TFAM promotes carcinogenesis of the prostate, and may constitute a marker to be used in the diagnosis and prognosis of prostate cancer.
Published: 1 January 2023
Genetic Testing and Molecular Biomarkers, Volume 27, pp 27-28; https://doi.org/10.1089/gtmb.2022.29064.ack

Abstract:
Genetic Testing and Molecular Biomarkers
Ruizhe Fan, Jiuzhou Zhao, Bo Wang, Xiang Li, Yuping Guan, Pengfei Ren, Rui Sun, Liya Zhang,
Published: 1 December 2022
Genetic Testing and Molecular Biomarkers, Volume 26, pp 582-588; https://doi.org/10.1089/gtmb.2022.0070

Abstract:
Aims: In this study, we determined whether different genotypes of drug-metabolizing enzymes are associated with the therapeutic effects of gefitinib in non-small cell lung cancer (NSCLC). Methods: A retrospective analysis of 112 patients with stage III or IV NSCLC was performed. The clinical characteristics of these patients, including progression-free survival (PFS), outcome of gefitinib treatment, and relationship between the genotypes of rs1065852/rs2242480 and prognosis, were analyzed. Results: The rs1065852 CT/TT genotype was associated with worse prognosis than the CC type (p = 0.0306), and the median PFS was lower than that with the CC type (287 days vs. 350 days). Compared with those with CC+CC genotypes, individuals carrying T alleles (CT/TT+CT/TT) at rs1065852/rs2242480 had a poorer prognosis, and the median PFS of CT/TT+CT/TT at rs1065852/rs2242480 was significantly lower than that of the CC+CC type (188 days vs. 444.5 days). Conclusions: Genotypes of the drug-metabolizing enzymes rs1065852 and rs2242480 have an impact on the prognosis of patients with NSCLC treated with gefitinib.
, Chunhai Gao, Lin Li, Liangqian Jiang, Yuda Wei, Fengyuan Che,
Published: 1 December 2022
Genetic Testing and Molecular Biomarkers, Volume 26, pp 589-594; https://doi.org/10.1089/gtmb.2022.0142

Abstract:
Purpose: To explore the genetic defects in two Chinese families with X-linked Norrie disease (ND). Methods: We analyzed two Chinese families with ND at molecular level through clinical exome sequencing and the variations were identified by Sanger sequencing. Results: Two genetic variations were found in the NDP gene by clinical exome sequencing, a partial deletion of 801 bp contained the whole exon 2 and a missense variant (164G>A) within codon 55 that resulted in the interchange of cysteine by phenylalanine. Clinical findings were more severe in the patients who presented the missense variant. Conclusion: We report two genetic variations in the NDP gene in Chinese that extend the mutational and phenotypic spectra of NDP gene, and also demonstrate the feasibility of clinical exome sequencing in application of molecular diagnosis.
Xiangyu Kong, Zhen He, Zhaohua Ji, Ting Fu, Xiaojie Yuan, Haowei Zhou, ,
Published: 1 December 2022
Genetic Testing and Molecular Biomarkers, Volume 26, pp 564-572; https://doi.org/10.1089/gtmb.2022.0128

Abstract:
Background: Liver cancer is one of the most frequently diagnosed malignant tumors, with an extremely high incidence rate. Diagnosis of liver cancer is difficult with the existing methods and improved biomarkers are urgently needed. A number of studies have established a link between abnormal miR-375 expression and liver cancer. Therefore, we conducted a systematic analysis to appraise whether miR-375 can be used as a screening tool for liver cancer detection. Methods: Through a systematic database search, studies investigating miR-375 expression in serum by the quantitative real-time reverse transcription-PCR (qRT-PCR) method were included in the study. A total of 1,100 participants (576 with liver cancer and 534 without liver cancer) were recruited. The efficacy of microRNA-375 in the detection of liver cancer was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under curve (AUC). Results: The pooled sensitivity and specificity of miR-375 in the detection of liver cancer were 0.91 (95% confidence interval [CI]: 0.74–0.98) and 0.83 (95% CI: 0.67–0.92), respectively. Furthermore, the pooled PLR was 5.40 (95% CI: 2.58–11.31), NLR was 0.10 (95% CI: 0.03–0.36), DOR was 52.52 (95% CI: 10.02–275.42), and AUC was 0.93 (95% CI: 0.90–0.95), indicating that miR-375 is effective at detecting liver cancer. Conclusions: According to our meta-analysis, measuring serum miR-375 has high sensitivity and specificity, which will facilitate its clinical application in liver cancer monitoring.
Peng Li, Xin Wen, Xiaoying Zhang, Fufang Wang, Dong Zhang,
Published: 1 December 2022
Genetic Testing and Molecular Biomarkers, Volume 26, pp 553-563; https://doi.org/10.1089/gtmb.2022.0102

Abstract:
Aim: To identify genes associated with the prognosis of head and neck squamous cell carcinoma (HNSC) and potential molecular targets for therapy. Materials and Methods: Gene Expression Profiling Interactive Analysis, Human Protein Atlas, University of ALabama at Birmingham CANcer, LinkedOmics, cBioPortal, Cell Counting Kit 8, and polymerase chain reaction were used in this study. Results: The expression level of nuclear transport factor 2 (NUTF2) was elevated in HNSC tissues and was associated with poor prognosis in HNSC patients. NUTF2-targeted intervention inhibited the proliferation of HNSC cells. SEC61G, which was positively correlated with NUTF2, was decreased in HNSC cells with NUTF2 suppression. Conclusions: NUTF2 may be correlated with the prognosis and development of HNSC, laying the foundation for future studies on the potential role of NUTF2 in HNSC.
Wenyan Zhang, Feng Jin, Ruolan Guo, Zhan Qi, Yaling Wang, Xueling Li, Yali Wu, Wei Li, , Chanjuan Hao
Published: 1 December 2022
Genetic Testing and Molecular Biomarkers, Volume 26, pp 573-581; https://doi.org/10.1089/gtmb.2022.0100

Abstract:
Background: Conventional newborn screening (NBS) is usually based on biochemical methods to predict the risk of inborn errors of metabolism. Recent studies have applied next-generation sequencing in NBS and revealed much more information, including carrier status. Whether these carriers of variants differ from other individuals was not fully determined. Objective: This research investigated the effect of heterozygous carrier status of pathogenic variants on biochemical indicators during NBS. Methods: We enrolled newborns participating in both conventional NBS and our previous Newborn Screening with Targeted Sequencing (NESTS) program from January 2021 to December 2021 in the Shunyi Maternal and Children's Hospital of Beijing Children's Hospital. Newborn levels of phenylalanine (Phe), thyroid stimulating hormone (TSH), and 17-hydroxyprogesterone (17-OHP) were measured to be analyzed together with associated sequencing results. Results: A total of 2351 newborns in the NESTS program was examined in the study. None had biallelic variants in genes related to congenital hypothyroidism (CH), hyperphenylalaninemia (HPA) or congenital adrenal hyperplasia. Forty-nine heterozygous carriers with phenylalanine hydroxylase (PAH) variants had significantly higher levels of Phe (p < 0.0001), and 11 heterozygous carriers of thyroid-stimulating hormone receptor (TSHR) variants had significantly higher levels of TSH (p < 0.05). Although heterozygous carriers had higher biochemical levels, they were below the diagnostic threshold of HPA and CH. Conclusions: Carriers of heterozygous variants in PAH or TSHR had significantly increased biochemical levels of associated factors in NBS. For individuals with higher Phe or TSH levels within the normal reference intervals, attention should be paid to the possibility of heterozygous carrier status.
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