<p><em>HNRNPCL1</em>, <em>PRAMEF1</em>, <em>CFAP74</em>, and <em>DFFB</em>: Common Potential Biomarkers for Sporadic and Suspected Lynch Syndrome Endometrial Cancer</p>

Abstract

To investigate the genes of patients with sporadic endometrial cancer (EC) and suspected Lynch syndrome (LS)-related EC in the Chinese population. Identification of meaningful mutation sites can provide theoretical basis for molecular targeted therapy, aiming to improve the prognosis of patients with EC. Methods: We recruited 388 patients with EC for mismatch repair (MMR) immunohistochemistry and MLH1 methylation analysis. Based on the results, they were divided into four groups: MMR without deletion group (sporadic EC group 1); MLH1&PMS2 deletion and MLH1 methylation group (sporadic EC group 2); MSH2 and/or MSH6 deletion group (suspected LS group); and unclassified group (remainder cases). Patients from each group were randomly screened for whole-exome sequencing detection. Genome Analysis Toolkit, VarScant, MuTect, and CONTRA were used to detect the insertions/deletions, single nucleotide polymorphisms, and copy number variations. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction analysis was accomplished through the STRING database. Results: The MMR immunohistochemistry results were positive (without MMR deletion) and negative in 299 patients and 89 patients, respectively. The 32, 10, 13, and 7 patients in the sporadic EC group 1, sporadic EC group 2, suspected LS group, and unclassified group were randomly selected for whole-exome sequencing, respectively. These three groups had a total of 86 common mutation sites, which were distributed on 26 genes. Among the top 30 common high-frequency mutation sites, 12, 5, 4, and 3 mutation sites were located on HNRNPCL1, PRAMEF1, HNRNPCL2, and CFAP74, respectively. Protein-protein interaction analysis showed that DFFB was associated with the most genes. There were some differences in the number of specific mutations in the families of different LS-related EC proband. Conclusion: HNRNPCL1, PRAMEF1, CFAP74, and DFFB may be potential biomarkers for EC or LS-related EC.

Transcriptome analysis of human preimplantation embryo reveals expressed waves associated with blastulation failure based on embryonic grade and age

“…Additionally, HNRNPCL1 (Q = 5.05 × 10 -20 ) and GCOM1 (Q = 1.08 × 10 -13 ), which are also involved in cancer, were highly upregulated in group EB and group UB respetively (Fig. 2B-2C) (Schinke et al 2014; Gao et al 2020). Together, these data suggest that preimplantation embryos with developmental arrest showed a lack of transcriptional control reminiscent of the hallmarks of cancer, and embryos arrested at the cleavage stage might be associated with unfulfilled mRNAs.…”

“…Interestingly, ZNF280A , a transcription factor, inactivates the Hippo signaling pathway-dependent proliferation and tumorigenesis in colorectal cancer, as the Hippo pathway plays a vital role in the initiation of TE fate in human embryo development (Wang et al 2019; Gerri et al 2020). PRAMEF1 is also a potential biomarker in cancer, and its upregulation may be associated with a lack of transcriptional control (Gao et al 2020). KLF17, a transcription repressor, is enriched in 8-cell, morula, as well as early blastocyst stages and might be associated with maternal genes in human embryos (Meistermann et al 2021).…”

“…Additionally, HNRNPCL1 (Q = 5.05 × 10 -20 ) and GCOM1 (Q = 1.08 × 10 -13 ), which are also involved in cancer, were highly upregulated in group EB and group UB respetively (Fig. 2B-2C) (Schinke et al 2014;Gao et al 2020).…”

An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines

“… FLYWCH-type zinc finger-containing protein 1 (PSLALP) has a possible tumor suppressive role in preventing colorectal cancer metastasis [ 35 ]. Heterogeneous nuclear ribonucleoprotein C-like 1 (DLQAIK, LQAIKQ, QAKQE), alterations of which are found in sporadic and suspected Lynch syndrome endometrial cancer [ 36 ]. Histone acetyltransferases KAT2A and KAT2B (DGRVIG), when altered, are associated with cardiovascular pathology [ 37 ].…”

“…Heterogeneous nuclear ribonucleoprotein C-like 1 (DLQAIK, LQAIKQ, QAKQE), alterations of which are found in sporadic and suspected Lynch syndrome endometrial cancer [ 36 ].…”