Marker For Diagnosis Of Cancer Research Articles

HER2 targeted structure prediction and analysis based on artificial intelligence

HER2 is a crucial marker in cancer diagnosis and targeted treatment. Accurate structure prediction and analysis of HER2 are vital for understanding its function and designing effective therapies. Our study proposes an end-to-end and artificial intelligence approach that uses deep learning frameworks to predict and analyze HER2s structure. Using top-notch machine learning algorithms, we trained a model on a comprehensive dataset of HER2 sequences and structures. The model showed impressive accuracy in forecasting HER2s tertiary structure, helping identify potential functional areas and critical interaction points. Moreover, our analysis provided new insights into HER2s structural changes and stability, revealing potential regulation mechanisms for targeted therapies. We used advanced bioinformatics tools to validate our predictions and ensure their reliability. This research marks a significant step in understanding HER2s molecular structure and lays a solid groundwork for personalized cancer treatments. By harnessing artificial intelligence, our study offers a promising path for precise medicine and targeted treatments for HER2-overexpressing cancers.

A Comprehensive Study of the CA-72.4 Tumor Marker Utilization and Cancer Detection: Analysis Based on Ministry of Health Data

Background: This study aims to explore the relevance and utilization of the CA 72.4 tumor marker in cancer diagnosis, with a particular focus on gastrointestinal tumors and ovarian cancer, based on data from the Minis-try of Health. Materials and Methods: We conducted a retrospective analysis of health records from the Ministry of Health spanning over five years. The data, consisting of various demographics, including gender, age, and clinical service requests, was statistically analyzed. The rates of reference range exceedance for the CA 72.4 tumor marker, diagnosis times, the ratio of cancer diagnosis, and the cost distribution were among the key aspects evaluated. Results: The analysis revealed a significant increase in the request for CA 72.4 tests over the years. It was also observed that cancer detection rates slightly increased over time, with a higher percentage in patients testing positive for CA 72.4, primarily requested before diagnosis. The highest requests for the test were made by the Medical Oncology clinic. Furthermore, it was observed that gender and age groups played significant roles in the prevalence of cancer diagnoses. Conclusions: Our study indicates that the use of CA 72.4 as a tumor marker could be valuable, especially in the detection of certain types of cancer. However, the correlation between a positive CA 72.4 test and a definitive cancer diagnosis requires further investigation, as the sensitivity and specificity of this marker are still subjects of debate. Despite certain limitations, this study offers substantial insights into the utility of CA 72.4 in the current healthcare setting.

GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers.

Cancer is a crucial public health problem and one of the leading causes of death worldwide. Previous studies have suggested that GPX3 may be involved in cancer metastasis and chemotherapy resistance. However, how GPX3 affects cancer patients' outcomes and the underlying mechanism remains unclear. Sequencing data and clinical data from TCGA, GTEx, HPA, and CPTAC were used to explore the relationship between GPX3 expression and clinical features. Immunoinfiltration scores were used to assess the relationship between GPX3 and the tumor immune microenvironment. Functional enrichment analysis was used to predict the role of GPX3 in tumors. Gene mutation frequency, methylation level, and histone modification were used to predict the GPX3 expression regulation method. Breast, ovarian, colon, and gastric cancer cells were used to investigate the relationship between GPX3 expression and cancer cell metastasis, proliferation, and chemotherapy sensitivity. GPX3 is down-regulated in various tumor tissues, and GPX3 expression level can be used as a marker for cancer diagnosis. However, GPX3 expression is associated with higher stage and lymph node metastasis, as well as poorer prognosis. GPX3 is closely related to thyroid function and antioxidant function, and its expression may be regulated by epigenetic inheritance such as methylation modification or histone modification. In vitro experiments, GPX3 expression is associated with cancer cell sensitivity to oxidant and platinum-based chemotherapy and is involved in tumor metastasis in oxidative environments. We explored the relationship between GPX3 and clinical features, immune infiltration characteristics, migration and metastasis, and chemotherapy sensitivities of human cancers. We further investigated the potential genetic and epigenetic regulation of GPX3 in cancer. Our results suggested that GPX3 plays a complicated role in the tumor microenvironment, simultaneously promoting metastasis and chemotherapy resistance in human cancers.

Glucometer Readout for Portable Detection of Heterogeneous Circulating Tumor Cells in Lung Cancer Captured on a Dual Aptamer Functionalized Wrinkled Cellulose Hydrogel Interface.

The rarity of circulating tumor cells (CTCs) poses a great challenge to their clinical application as reliable "liquid biopsy" markers for cancer diagnosis. Meanwhile, the epithelial-mesenchymal transition (EMT) led to a reduced efficiency in capturing cells with lost or downregulated epithelial cell adhesion molecule (EpCAM) expressions. In this study, we proposed an integrated, highly efficient strategy for heterogeneous CTC capture and portable detection from the blood of non-small-cell lung cancer (NSCLC) patients. First, the cellulose wrinkled hydrogel with excellent biocompatibility and high specific area was employed as the biointerface to capture heterogeneous CTCs with an improved capture efficiency in virtue of dual targeting against epithelial and mesenchymal ones. Meanwhile, the strategy of glucometer readout was introduced for the quantification of captured CTCs on the same hydrogel interface by a detection probe, Au-G-MSN-Apt, which was fabricated via entrapping glucose into the amino group functionalized mesoporous silica nanoparticle (MSN) framework sealed by l-cysteine modified gold nanoparticles (AuNPs) and then linked with dual aptamers of EpCAM and Vimentin. The number of captured CTCs on the hydrogel could be reflected according to the portable glucose meter (PGM) readings. Moreover, it was found that the captured cells maintained a higher viability on the hydrogel and could be in situ recultured without releasing from the substrate. Finally, this integrated strategy was successfully applied to inspect the correlations between the number of heterogeneous CTCs in the blood of NSCLC patients with disease stage and whether there was distant metastasis.

Changes of serum protein N-glycosylation in cancer.

Glycosylation is a posttranslational modification responsible for many bio-logical processes including protein-protein interactions, cell signaling or cell cycle regulation. Changes in glycosylation of serum proteins reflects the status of tissues and cells in the organism and therefore can be used as markers for dia-gnosis of cancer, its progression and determination of its subtypes. N-glycan profiling is often used for characterization of N-glycosylation changes. It is based on the measurements of N-glycans released from the serum proteins. Beside the N-glycan profiling, glycoproteomic approach is emerging as it preserves the information about glycan composition, original protein, and its glycosylation sites. This review covers existing works describing the changes in serum protein N-glycosylation in various cancer types. Attention was paid to both the glycomic and glycoproteomic approaches. The last part of the review shortly presents the analytical methods used for these analyses.

Abstract 3242: The role of SERPINE1 in trametinib resistance in low-grade ovarian serous cancer cell line

Abstract Ovarian cancer is the deadliest gynecological cancer. The dismal 5-year survival rate is partly due to late-stage diagnosis. MEK inhibition therapy has been approved by FDA as treatment option for several cancer types. Recently, trametinib has achieved significantly better objective response rate than traditional standard of care therapies in patients with recurrent low-grade ovarian serous cancer (LGOSC). However, adaptive resistance to MEK inhibitors is common and the mechanism is still unclear. To further investigate the mechanism of adaptive resistance, we have established several adaptive trametinib resistant ovarian cancer cell lines. Our result showed that SERPINE1 was significantly induced in a LGOSC cell line, HOC-7, after acquiring trametinib resistance. To determine the role of SERPINE1 in trametinib resistance in LGOSC, overexpression and down-regulation of SERPINE1 in HOC-7 were achieved by transfection with a cDNA clone expressing SERPINE1 and siRNA silencing respectively. The association of SERPINE1 with trametinib resistance was also investigated in a LGOSC mouse model. For in vitro studies, HOC-7 overexpressing SERPINE1 had a 5-fold increase in IC50 to trametinib in comparison to the parental control cell line HOC-7. Furthermore, pERK expression was also up-regulated in HOC-7 overexpressing SERPINE1. By knocking down the expression of SERIPINE1 in trametinib adaptive resistant HOC-7 cells transfected with SERPINE1 siRNA, we found that the cell proliferation was partly reduced in comparison to cells transfected with control siRNA. More importantly, the trametinib adaptive resistant cells became more sensitive to trametinib. For in vivo studies with the LGOSC mouse model, we found that SERPINE1 expression increased after trametinib treatment in LGOSC tumor tissue. Interestingly, the expression of SERPINE1 protein was found to be correlated to ERK phosphorylation in tumor tissues. Furthermore, the measurement of plasma SERPINE1 in LGOSC mouse model and cancer patient revealed that SERPINE1 could be a predictive marker in cancer diagnosis and prognosis. The above observations were further supported by CCLE and TCGA data that SERPINE1 gene expression level correlated with trametinib sensitivity and patient survival. In conclusion, SERPINE1 could facilitate trametinib resistance by ERK phosphorylation, and this protein has the potential to be a therapeutic target, diagnostic and prognostic biomarker for LGOSC. Further analysis by RNA-seq and immunohistochemical staining of trametinib-treated mouse tumor samples will be performed to understand the mechanism of MEK inhibitor adaptive resistance. Citation Format: Chun Wai Ng, Yvonne TM Tsang, David M. Gershenson, Kwong-Kwok Wong. The role of SERPINE1 in trametinib resistance in low-grade ovarian serous cancer cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3242.

Plasma extracellular vesicle long RNA profiles in the diagnosis and prediction of treatment response for breast cancer

A large number RNAs are enriched and stable in extracellular vesicles (EVs), and they can reflect their tissue origins and are suitable as liquid biopsy markers for cancer diagnosis and treatment efficacy prediction. In this study, we used extracellular vesicle long RNA (exLR) sequencing to characterize the plasma-derived exLRs from 112 breast cancer patients, 19 benign patients and 41 healthy participants. The different exLRs profiling was found between the breast cancer and non-cancer groups. Thus, we constructed a breast cancer diagnostic signature which showed high accuracy with an area under the curve (AUC) of 0.960 in the training cohort and 0.900 in the validation cohort. The signature was able to identify early stage BC (I/II) with an AUC of 0.940. Integrating the signature with breast imaging could increase the diagnosis accuracy for breast cancer patients. Moreover, we enrolled 58 patients who received neoadjuvant treatment and identified an exLR (exMSMO1), which could distinguish pathological complete response (pCR) patients from non-pCR with an AUC of 0.790. Silencing MSMO1 could significantly enhance the sensitivity of MDA-MB-231 cells to paclitaxel and doxorubicin through modulating mTORC1 signaling pathway. This study demonstrated the value of exLR profiling to provide potential biomarkers for early detection and treatment efficacy prediction of breast cancer.

Label-free and highly sensitive nanoplasmonic biosensor-based autophagy flux sensing for clinical application

Autophagy is a cellular catabolic process that plays significant roles in various diseases such as neurodegenerative diseases, infectious diseases, and cancers. The importance of microtubule-associated protein 1 light chain 3 (LC3) quantification is highlighted because it is a precise tool for measuring autophagy and is also known to be associated with cancer progression, functioning as a clinically significant marker in cancer diagnosis and prognosis. To date, the quest continues to develop an autophagic LC3 detection method with enhanced sensitivity, and which provides a means of quantification to meet the clinical application needs. Here, we present a simple and intuitive autophagy flux measurement by a single gold nanoparticle-based LC3 sensing platform. This nanoplasmonic sensor does not require additional labeling, consisted of only gold nanorods and monoclonal antibodies, which enables rapid total LC3 quantification within a wide dynamic concentration range, with a detection limit of 64.1 fM. Moreover, the sensing ability of the proposed biosensor in cell lysates mimicking clinical samples and human cancer cell lysates was proved by providing a simple autophagic flux analysis method based on LSPR shifts. This sensor is the first label-free, highly sensitive total LC3 quantification nanoplasmonic biosensor that can be used for autophagy measurement, employed for precise cancer diagnosis in combination with other biomarkers. It can serve as an effective tool for determining therapeutic drug dosage in the future.

MicroRNA-320a Promotes Epithelial Ovarian Cancer Cell Proliferation and Invasion by Targeting RASSF8.

MicroRNAs (miRNAs) play important roles in tumorigenesis by controlling target gene expression. With opposing roles as a tumor suppressor or oncogene, microRNA-320a (miR-320a) was found to participate in tumor genesis and progression and also identified as a potentially useful marker in cancer diagnosis, treatment, and prognosis. To better understand the role of miR-320a in ovarian cancer, we investigated miR-320a expression in epithelial ovarian cancer (EOC) specimens as well as EOC cell lines and analyzed correlations between miR-320a expression and processes associated with EOC progression. The miR-320a level in EOC specimens was found to be associated with ovarian cancer progression and infiltration. Through in vitro and in vivo studies, we found that miR-320a significantly promoted the proliferation, migration, and invasion of EOC cells, and we identified RASSF8 as a target gene of miR-320a that was downregulated in EOC tissues and cell lines. In vitro downregulation of RASSF8 promoted the growth, migration, and invasion of EOC cells. Together these findings indicate that RASSF8 is a direct target of miR-320a, through which miR-320a promotes the progression of EOC.

The Oncogenic Functions of Insulin-like Growth Factor 2 mRNA-Binding Protein 3 in Human Carcinomas.

IGF2BP3 (also known as IMP3, KOC), a member of the insulin-like growth factor mRNA-binding protein family (IMPs), has been a research target in recent studies of promoting embryo development and exacerbating cancer. IGF2BP3 is ubiquitously expressed in early embryogenesis stages but limited in postembryonic stages, which is important in many physiological aspects such as stem cell renewal, morphological development and metabolism. A large number of studies show that IGF2BP3 interacts with many kinds of non-coding RNAs and proteins to promote cancer cell proliferation and metastasis and inhibit cancer cell apoptosis. As IGF2BP3 is highly expressed in advanced cancers and associated with poor overall survival rates of patients, it may be a potential molecular marker in cancer diagnosis for the detection of cancerous tissues and an indicator of cancer stages. Therefore, anti-IGF2BP3 drugs or monoclonal antibodies are expected as new therapeutic methods in cancer treatment. This review summarizes recent findings among IGF2BP3, RNA and proteins in cancer processes, with a focus on its cancer-promoting mechanisms and potential application as a new biomarker for cancer diagnosis and treatment.

Abstract 2012: Recurrent rearrangements of NAALADL2 in prostate, breast, cervical, head and neck and lung squamous cell carcinoma

Abstract Prostate cancer is a heterogeneous disease with unique molecular aberrations present in patient sub-groups. Distinct prostate cancer molecular changes have been shown to associate with specific clinical outcomes, suggesting the potential of molecular markers as diagnostic and prognostic biomarkers for prostate cancer. Recurrent ETS family gene fusions, BRAF and SPINK1 overexpression account for about 50-60% of the prostate cancer cases. Genetic aberrations in the remaining 40-50% of the cases is not known. Our attempt to identify new molecular markers in prostate cancer led to the identification of NAALADL2 gene shown to be associated with aggressive prostate cancer. In this study, we carried out a comprehensive analysis of genomic changes of NAALADL2 in prostate and other solid cancers by analyzing copy number changes and gene expression using TCGA next generation RNA sequencing data. We observed recurrent amplification, rearrangement, deletion, mutations and over-expression of NAALADL2 in prostate cancer cases. Notably, we observed mutually exclusive aberrations in NAALADL2 when compared to other cases with known prostate cancer aberrations including ETS gene fusions, indicating NAALADL2 as a distinct molecular sub-set of prostate cancer. Independent validation by fluorescent in situ hybridization (FISH) analysis using break apart probe for NAALADL2 on 874 prostate cancer revealed recurrent amplification and rearrangements in about 8% (71/874) [PN1] of the cases with higher prevalence in Caucasian American than African American cases. Based on these results, we explored prostate cancer TGCA gene fusion database and identified additional cases with gene fusions involving NAALADL2. We selected one of the gene fusions identified in the TCGA database involving NAALADL2-PIK3CA and conducted in vitro functional characterization studies and showed its oncogenic properties. Gene expression microarray analysis of RWPE1 cells transfected with NAALADL2-PIK3CA showed dysregulation of genes involved in cancer related pathways, further suggesting a role for NAALADL2-PIK3CA in prostate cancer development. Based on these studies, we explored the incidence of NAALADL2 gene fusion in other solid cancers including lung squamous cell cancer (LUSC), ovarian cancer, head and neck cancer, cervical cancer and breast cancer shown to have recurrent gene fusions identified in the TCGA gene fusion database. Notably, recurrent rearrangements and amplification are seen in a large subset (45%) of LUSC patients, but not in lung adenocarcinoma, suggesting that NAALADL2 could be developed as a novel biomarker in LUSC. Further validation studies using FISH in our independent cohort of LUSC and breast cancer patients including 79 patients from Ghana confirmed recurrent rearrangements and amplification in a subset of cases. In conclusion, similar to ERG, BRAF and FGFR genes, we show recurrent gene fusions of NAALADL2 across multiple solid cancer with potential applications as a pan cancer molecular marker for cancer diagnosis and a potential target for drug development. Citation Format: Pavithra D. Arachchige, Shannon Carskadon, James Hu, Justin Fernando, Darshan S. Chandrashekar, Nilesh S. Gupta, Sean R. Williamson, Dhananjay A. Chitale, Craig G. Rogers, James O. Peabody, Mani Menon, Tarek A. Bismar, Evelyn Jiagge, Sooryanarayana Varambally, Nallasivam Palanisamy. Recurrent rearrangements of NAALADL2 in prostate, breast, cervical, head and neck and lung squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2012.

Breast cancer diagnosis by analysis of serum N-glycans using MALDI-TOF mass spectroscopy.

Blood and serum N-glycans can be used as markers for cancer diagnosis, as alterations in protein glycosylation are associated with cancer pathogenesis and progression. We aimed to develop a platform for breast cancer (BrC) diagnosis based on serum N-glycan profiles using MALDI-TOF mass spectroscopy. Serum N-glycans from BrC patients and healthy volunteers were evaluated using NosQuest’s software “NosIDsys.” BrC-associated “NosID” N-glycan biomarkers were selected based on abundance and NosIDsys analysis, and their diagnostic potential was determined using NosIDsys and receiver operating characteristic curves. Results showed an efficient pattern recognition of invasive ductal carcinoma patients, with very high diagnostic performance [area under the curve (AUC): 0.93 and 95% confidence interval (CI): 0.917–0.947]. We achieved effective stage-specific differentiation of BrC patients from healthy controls with 82.3% specificity, 84.1% sensitivity, and 82.8% accuracy for stage 1 BrC and recognized hormone receptor-2 and lymph node invasion subtypes based on N-glycan profiles. Our novel technique supplements conventional diagnostic strategies for BrC detection and can be developed as an independent platform for BrC screening.

Strained Conformations of Nucleosides in Active Sites of Nucleoside Phosphorylases.

Nucleoside phosphorylases catalyze the reversible phosphorolysis of nucleosides to heterocyclic bases, giving α-d-ribose-1-phosphate or α-d-2-deoxyribose-1-phosphate. These enzymes are involved in salvage pathways of nucleoside biosynthesis. The level of these enzymes is often elevated in tumors, which can be used as a marker for cancer diagnosis. This review presents the analysis of conformations of nucleosides and their analogues in complexes with nucleoside phosphorylases of the first (NP-1) family, which includes hexameric and trimeric purine nucleoside phosphorylases (EC 2.4.2.1), hexameric and trimeric 5′-deoxy-5′-methylthioadenosine phosphorylases (EC 2.4.2.28), and uridine phosphorylases (EC 2.4.2.3). Nucleosides adopt similar conformations in complexes, with these conformations being significantly different from those of free nucleosides. In complexes, pentofuranose rings of all nucleosides are at the W region of the pseudorotation cycle that corresponds to the energy barrier to the N↔S interconversion. In most of the complexes, the orientation of the bases with respect to the ribose is in the high-syn region in the immediate vicinity of the barrier to syn ↔ anti transitions. Such conformations of nucleosides in complexes are unfavorable when compared to free nucleosides and they are stabilized by interactions with the enzyme. The sulfate (or phosphate) ion in the active site of the complexes influences the conformation of the furanose ring. The binding of nucleosides in strained conformations is a characteristic feature of the enzyme–substrate complex formation for this enzyme group.

Emerging Role of Protein Post-Translational Modification in the Potential Clinical Application of Cancer

Cancer, one of the largest public health problems in the world, greatly endangers human health. Every country in the world faces a significant burden due to cancer. Protein post-translational modification (PTM) plays a very important role in life. PTM makes the structure of proteins more complex and the functions more perfect. Common PTM processes include methylation, acetylation, phosphorylation, glycosylation and ubiquitination. In this paper, we introduce several common types of PTMs that were discovered in recent years in various cancer types, especially the early stages of cancer, and we explore the role of related molecules in cancer screening, diagnosis, disease surveillance and prognosis. We look forward to using PTM-relevant molecules as markers for the early diagnosis of cancer, after further in-depth research and large-scale clinical trials, to contribute to the early and accurate diagnosis of cancer, thereby improving the prognosis.

PreMSIm: An R package for predicting microsatellite instability from the expression profiling of a gene panel in cancer

Microsatellite instability (MSI) is a genomic property of the cancers with defective DNA mismatch repair and is a useful marker for cancer diagnosis and treatment in diverse cancer types. In particular, MSI has been associated with the active immune checkpoint blockade therapy response in cancer. Most of computational methods for predicting MSI are based on DNA sequencing data and a few are based on mRNA expression data. Using the RNA-Seq pan-cancer datasets for three cancer cohorts (colon, gastric, and endometrial cancers) from The Cancer Genome Atlas (TCGA) program, we developed an algorithm (PreMSIm) for predicting MSI from the expression profiling of a 15-gene panel in cancer. We demonstrated that PreMSIm had high prediction performance in predicting MSI in most cases using both RNA-Seq and microarray gene expression datasets. Moreover, PreMSIm displayed superior or comparable performance versus other DNA or mRNA-based methods. We conclude that PreMSIm has the potential to provide an alternative approach for identifying MSI in cancer.

The diagnostic role of A-kinase anchoring protein 12, Bcl-2 and high mobility group box Protein-1 levels in breast cancer

Abstract Aim Despite the improved diagnosis and treatment methods in recent years, the number of new breast cancer cases does not reduce and the mortality rates are still so high. There are several proteins that play significant roles in carcinogenesis process and hold a great potential to be used as a marker of cancer diagnosis. A-Kinase Anchoring Protein 12 (AKAP12) regulates gene expression in cell cycle and apoptosis while B- cell Lymphoma 2 (BCL2) family proteins and inhibitors of apoptosis proteins are the major regulators of the apoptotic process. High mobility group box 1 (HMGB1) has multiple pro-tumor roles in tumor development. In our study, we aimed to determine the usability and sensitivity of AKAP12, BCL2 and HMGB1 proteins as a marker of breast cancer diagnosis, and further investigate the relationship among these proteins. Material and Methods Between 2014 and 2017, a total number of 82 participants, 60 of them were diagnosed with early stage breast cancer and 22 healthy age-matched people as control group, were included in the study. Serum samples obtained from the groups were investigated in terms of AKAP12, BCL2 and HMGB1 levels by using Enzyme Linked Immuno-Sorbent Assay (ELISA) method. Results Comparing the patient group with control groups, AKAP12, BCL2 and HMGB1 levels were found to be significantly higher in the patient group (p = 0.009), (p Conclusion The findings of our results indicate that these proteins levels may be used as markers in the diagnosis and follow-up of breast cancer.

AIE-active polysiloxane-based fluorescent probe for identifying cancer cells by locating lipid drops

Comparing with normal cells, Lipid droplets (LDs) of cancer cells show lower polarity and less quantity, which can be utilized as a marker for cancer diagnosis. However, the investigation of LDs in living cancer cells is restricted by the lack of effective molecular tools. Herein, we first reported a novel polysiloxane-based polymer fluorescent polar probe TR-1 with AIE properties, which realized the possibilities for locating LDs. It can aggregate in the LDs of cancer cells and show a stronger fluorescent signal to conduct cancer diagnosis. Moreover, the excellent photostability of TR-1 enable stable fluorescence to exhibit in cancer cells during effective time.

Rap GTPase Interactor: A Potential Marker for Cancer Prognosis Following Kidney Transplantation.

Post-transplant (post-Tx) kidney cancer has become the second-highest cause of death in kidney recipients. Late diagnosis and treatment are the main reasons for high mortality. Further research into early diagnosis and potential treatment is therefore required. In this current study, through genome-wide RNA-Seq profile analysis of post-Tx malignant blood samples and post-Tx non-malignant control blood samples (CTRL-Tx), we found Rap GTPase Interactor (RADIL) and Aprataxin (APTX) to be the most meaningful markers for cancer diagnosis. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of the RADIL-APTX signature model was 0.92 (P < 0.0001). Similarly, the AUC of RADIL alone was 0.91 (P < 0.0001) and that of APTX was 0.81 (P = 0.001). Additionally, using a semi-supervised method, we found that RADIL alone could better predict malignancies in kidney transplantation recipients than APTX alone. Kaplan-Meier analysis indicated that RADIL was expressed significantly higher in the early stages (I and II) of kidney, liver, stomach, and pancreatic cancer, suggesting the potential use of RADIL in early diagnosis. Multivariable Cox regression analysis found that RADIL together with other factors (including age, stage III, stage IV and CD8+ T cells) play a key role in kidney cancer development. Among those factors, RADIL could promote kidney cancer development (HR > 1, P < 0.05) while CD8+ T cells could inhibit kidney cancer development (HR < 1, P < 0.05). RADIL may be a new immunotherapy target for kidney cancer post kidney transplantation.

Targeting p53 as a promising therapeutic option for cancer by re-activating the wt or mutant p53's tumor suppression.

p53 protein, a product of the TP53 tumor suppressor gene, controls the cellular genome's integrity and is an important regulator of cell cycling, proliferation, apoptosis and metabolism. Mutations of TP53 or inactivation of its gene product are among the first events initiating malignant transformation. The consequent loss of control over the cell cycle, resulting in accelerated cell proliferation and facilitating metabolic reprogramming, gives the initiated (premalignant) cells numerous advantages over healthy cells. Interestingly, p53 status is not only an important marker in cancer diagnosis; it has also become a promising target of personalized therapy. Depending on the TP53 status different therapeutic options have been developed. (Re)-activation of p53 functionality in cancer cells offers promising new alternatives to existing oncological therapies.

Structural characteristics of natural chimeric genes and their implications for gene design.

The natural chimeric gene is a novel gene fused by two or more independent genes. Its discovery extends the classical gene concept that one gene resides in one chromosomal locus. During tumorigenesis, many chimeric genes lead to tumor-related diseases; therefore, it is one molecular marker for cancer diagnosis. In this review, we summarize the research progress of chimeric genes in terms of their feature, structure, transcription, regulation and function. We pinpoint the difficulties and challenges in the current research work, and discuss the application of chimeric gene in the new gene design.