Survival Of Patients Research Articles

Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer.

In epithelial ovarian cancer (EOC), platinum resistance, potentially mediated by cancer stem cells (CSCs), often leads to relapse and treatment failure. Here, the role of spindle pole body component 25 (SPC25) as a key determinant promoting stemness and platinum resistance in EOC cells, with its expression being correlated with adverse clinical outcomes is delineated. Mechanistically, SPC25 acts as a scaffolding platform, orchestrating the assembly of an SPC25/RIOK1/MYH9 trimeric complex, triggering RIOK1-mediated phosphorylation of MYH9 at Ser1943. This prompts MYH9 to disengage from the cytoskeleton, augmenting its nuclear accumulation, thus potentiating CTNNB1 transcription and subsequent activation of Wnt/β-catenin signaling. CBP1, a competitive inhibitory peptide, can disrupt the formation of the aforementioned trimeric complex, diminishing the activity of the SPC25/RIOK1/MYH9 axis-mediated Wnt/β-catenin signaling, and thus attenuate CSC phenotypes, thereby enhancing platinum efficacy in vitro, in vivo, and in patient-derived organoids. Therefore, targeting the SPC25/RIOK1/MYH9 axis, which mediates the maintenance of stemness and platinum resistance in EOC cells, may enhance platinum sensitivity and increase survival in patients with EOC.

Peptide Receptor Radionuclide Therapy and clinical associations with renal and hematological toxicities and survival in patients with neuroendocrine tumors: an analysis from two U.S. medical centers

PurposeRenal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT.MethodsA retrospective cohort of 448 NET patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions.ResultsOf the 448 PRRT treated patients, 335 received 177Lu-DOTATATE (74.78%) and 113 were treated with 90Y-DOTATOC (25.22%). Comparing patients treated with 177Lu-DOTATATE to those treated with 90Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with 90Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with 177Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received 177Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28–0.79, P = 0.004) compared with 90Y-DOTATOC, but there was no difference in OS.ConclusionThere was no significant renal, but minor hematological toxicity, in patients treated with 177Lu-DOTATATE compared with 90Y-DOTATOC. Compared to 90Y-DOTATOC, 177Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with 177Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.

TLR3 activation enhances antitumor effects of sorafenib in hepatocellular carcinoma by activating NK cell functions through ERK and NF-κB pathways

Background Sorafenib is a standard therapeutic agent for advanced hepatocellular carcinoma (HCC). However, its efficacy is moderate, as the survival of patients is prolonged for only a few months, and the response rate is low. The mechanism of low efficacy remains unclear. In this study, we investigated the effect of Toll-like receptor 3 (TLR3) on the effects of sorafenib on HCC. Methods Polyinosinic-polycytidylic acid [poly(I: C)] was used as a double-stranded RNA analog and TLR3 agonist in subsequent experiments. After orthotopic implantation of HCC tumors in BALBc nu/nu or C57BL/6 mice, survival time, tumor growth, and metastasis in the abdomen and lungs were analyzed. Flow cytometry and cytotoxicity assays were used to analyze NK cells isolated from the spleen or peripheral blood. ELISA was used to detect the expression of plasma interferon (IFN)-γ and monocyte chemoattractant protein (MCP)-1. In addition, the expression of phosphorylated-extracellular regulated kinase 1/2 (pERK1/2), phosphorylated-protein kinase B (pAKT), ERK1/2 and AKT was analyzed by Western blotting. Results Sorafenib reduced the number and activity of NK cells in tumor-bearing mice and simultaneously decreased the levels of MCP-1 and IFN-γ in the plasma. The combination of sorafenib and poly(I: C) synergistically inhibited tumor growth and metastasis in tumor xenograft mice and prolonged survival. Poly(I: C) not only exerts a direct inhibitory effect on tumor growth and metastasis by targeting the TLR3 receptor on tumor cells but also facilitates the proliferation and activation of NK cells, indirectly impeding tumor progression. Mechanistically, poly(I: C) decreased the sorafenib-induced inhibition of ERK phosphorylation and increased the phosphorylation of IκB in NK cells, thereby enhancing NK cell function. Conclusion Activation of TLR3 can enhance the antitumor effect of sorafenib on HCC. The combination of a TLR3 activator and sorafenib may be a new strategy for the treatment of HCC.

Development and validation of a nomogram for predicting overall survival of head and neck adenoid cystic carcinoma

This study aimed to develop and validate a nomogram using clinical variables to guide personalized treatment strategies for adenoid cystic carcinoma of the head and neck (ACCHN). Data from 1069 patients with ACCHN diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were used to construct the nomogram. External validation was performed using an independent cohort of 70 patients from Fujian Cancer Hospital. Multivariate Cox regression analysis was conducted using IBM SPSS version 26.0 and R Software version 4.2.3. The concordance index (C-index) and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the nomogram. Age, tumor site, surgery, N stage, M stage, and TNM stage were identified as independent prognostic factors through univariate and multivariate Cox analyses. The nomogram demonstrated superior predictive performance compared to the TNM staging system, effectively stratifying patients into high-risk and low-risk groups. This nomogram offers a valuable tool for predicting overall survival in patients with ACCHN and tailoring individualized treatment approaches.

Promising biomarker panel to monitor therapeutic efficacy of neoadjuvant chemotherapy in pancreatic cancer patients.

Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients. This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival. Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months). A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment.

Physical activity and renal outcome in diabetic and non-diabetic patients with chronic kidney disease stage G3b to G5

The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR] < 45 ml/min/1.73m2) is poorly studied. We examined this association in patients with advanced CKD in Japan. We used the Rapid Assessment of Physical Activity to assess baseline physical activity and classify patients as active or inactive. CKD progression was defined as 40% decline in eGFR, eGFR < 10, or requiring dialysis or transplantation. Among the 1,808 eligible patients, after adjusting for possible confounders, hazard ratios (HRs) for poor renal outcome in the active group were 0.68 (95% CI, 0.44–1.04), 1.09 (0.86–1.38), and 1.01 (0.82–1.25) in CKD stage G3b, G4, and G5, respectively, suggesting a renal benefit of exercise in CKD stage G3b. Adjusted HRs for death were 0.79 (0.40–1.57), 0.55 (0.38–0.80), and 0.75 (0.44–1.26) in stage G3b, G4, and G5, respectively. While the adjusted HRs of death were 0.84 (0.52–1.38) and 0.60 (0.43–0.83) in diabetic and non-diabetic patients, suggesting that exercise may reduce mortality in non-diabetic patients. Our study suggests that exercise is associated with better survival in non-diabetic patients with CKD stage G3b-5, and better renal outcome in diabetic and non-diabetic CKD stage G3b.

Association between KRAS mutation and alcohol consumption in Brazilian patients with colorectal cancer

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Detection before metastasis and efficient treatment of disease significantly improve patient survival and quality of life. However, limitations in diagnosis and postoperative surveillance are associated with low CRC detection and survival rates. Thus, this project aimed to evaluate the molecular profile of patients diagnosed with CRC, as molecular biomarkers constitute a new frontier for diagnosis, treatment and prognosis. Methods and Results: 42 patients were included in the study, predominantly male (59.5%), with a median age of 63 years (SD: 10.0; min: 41; max: 83). The majority of primary tumors were located in the rectum (38.1%), in the sigmoid (33.3%) and in the ascending (21.4%) colon. We evaluated the genes KRAS, NRAS, BRAF, EGFR and TP53 using Sanger sequencing. Somatic and germline mutations were found in the KRAS, EGFR and TP53 genes, with the most common somatic alteration being rs121913529 in KRAS. This variant was also strongly associated with alcoholism (p = 0.002). Furthermore, patients with somatic mutations in TP53 had significantly higher mortality compared to those with wild-type alleles (OR: 11.2; 95% CI 1.25–2.45). Conclusions: Our findings support a relationship between alcohol consumption and the rs121913529 mutation, which is classified as pathogenic for colorectal cancer. Thus, further studies investigating the link between alcohol consumption, colorectal carcinogenesis and tumor progression ought to be conducted.

Ly6E on tumor cells impairs anti-tumor T-cell responses: a novel mechanism of tumor-induced immune exclusion

BackgroundLymphocyte antigen 6 complex, locus E (Ly6E) has been initially demonstrated to involve in T cell activity and impair viral infectivity. Recently, high expression levels of Ly6E have been reported in tumor microenvironment (TME) of various types of cancers. However, the immunoregulatory mechanism of Ly6E manipulating TME remains unknown.MethodsTCGA database and Kaplan–Meier plotter database were used to evaluate the correlation between Ly6E expression levels and cancer patient survival. After analyzing Ly6E expression levels in human breast cancer tissues and tumor cell lines, we generated Ly6E knockout (KO) and overexpression (OE) mouse cell lines. Cell proliferation ability in vitro and the ability of growth and metastasis in mouse tumor models were compared between KO/OE and wild-type tumor cells. On day 7 after tumor implantation, tumor tissues were separated for flow cytometric assay, bulk RNA sequencing and single-cell RNA sequencing (ScRNA-seq). The role of Ly6E-expressing tumor cell on macrophage was analyzed in vitro.ResultsOur result surprisingly found that high Ly6E expression levels were associated with CD8+ T cell exclusion in tumor tissues and resistance to immunotherapy. Our data showed that knockout of Ly6E in tumor cells prompts tumor regression and inhibits tumor metastases, and Ly6E-OE tumor cells vice versa. The enhanced anti-tumor effect of Ly6E knockout in tumor cells was dependent on T cell response and formed long-lasting memory. The increase in the CD8+ T-cell infiltration into the tumor islet of Ly6E-KO tumors confirmed the role of Ly6E on T cell exclusion. ScRNA-seq analysis showed that M2 macrophages are particularly abundant in the Ly6E-expressing tumor tissues, especially M2-4 macrophage cluster identified by high levels of Arg-1, indicates that Ly6E-expressing tumor cells might restrict T cell infiltration via M2 macrophages. Moreover, in vitro assay showed that cell culture media derived from Ly6E-positive tumor cells promoted macrophage migration and M2 polarization.ConclusionOur study illuminated that Ly6E-expressing tumor cells facilitated the accumulation of M2 macrophages in TME, which contributes to CD8+ T cell exclusion and provides new insights for improving efficacy of cancer immunotherapy.

Development and Validation of a Predictive Nomogram for Patients With Myxopapillary Ependymoma: A Surveillance, Epidemiology, and End Results (SEER) Retrospective Cohort Analysis.

Retrospective Study. Myxopapillary ependymomas (MPEs) are a unique subgroup of spinal ependymomas originating from the filum terminale's ependymal glia. The 2021 WHO classification reclassified all MPEs as grade 2, recognizing their higher recurrence risk. Due to their rarity, our objective with this study is to understand MPEs' clinical course and optimal management through a large retrospective cohort analysis. From the years 2000 to 2020, patients with MPEs were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariable Cox proportional hazard models were run to identify variables that had a significant impact on the primary endpoint of overall survival (OS). A predictive nomogram was built to predict 5-year and 10-year survival probability. This retrospective cohort includes 1373 patients. Patients 65 years or older at diagnosis had a poorer OS (P < 0.001). Most patients received subtotal resection. Only 320 patients (23%) received gross total resection (GTR). Patients that received GTR had the best OS when compared against all other modalities of treatment (P < 0.05). Receiving radiotherapy did not affect OS in patients with MPE (P = 0.2). Nomogram includes patient age and treatment modalities, demonstrating acceptable accuracy in estimating the survival probability at 5-year and 10-year intervals, with a C-index of 0.80 (95% CI of 0.71 to 0.90). This study highlights the survival benefit of GTR in the treatment of patients with MPE. The role of adjuvant radiotherapy remains unclear as it did not seem to improve OS. The nomogram stratifies the risk of survival in patients with MPE based on age and treatment modality.

Interim post-progression data and updated survival in patients with newly diagnosed advanced ovarian cancer in ATHENA-MONO

Interim post-progression data and updated survival in patients with newly diagnosed advanced ovarian cancer in ATHENA-MONO

Spatial context of immune checkpoints as predictors of overall survival in patients with resectable colorectal cancer independent of standard TNM stages.

While immune checkpoint blockade (ICB) therapy has shown promising results in a small subset of colorectal cancer patients with high microsatellite instability (MSI-H), the majority of patients with colorectal cancer do not respond to ICB therapy. The main obstacle to the success of immunotherapy in cancer treatment is the exhaustion of tumor-infiltrating lymphocytes (TILs). Elucidating the spatial organization of immune checkpoints within the tumor microenvironment could pave the way for the development of novel prognostic tools and therapeutic strategies to enhance antitumor immune responses. To clarify the spatial and functional diversity of tumor-infiltrating lymphocytes (TILs) in the colorectal tumor microenvironment (TME), we performed multiplexed IHC to examine the exhaustion of TILs in the TME (the expression of PD-1 and TIM-3 (T-cell immunoglobulin and mucin-domain-containing protein 3), which are major biomarkers of T-cell exhaustion) and Lasso-Cox analyses of the correlation between CRC prognosis and TME features. For proof of concept, the antitumor efficacy of TIM-3 and PD-1 dual blockade in CRC was further evaluated in a CT26 subcutaneous tumor model of human CRC. We found that the spatial context of PD-1 and TIM-3 successfully predicted the overall survival of CRC patients independent of TNM stage. Dual targeting of PD-1 and TIM-3 in mouse tumor models inhibited tumor progression and reduced T-cell exhaustion, indicating a potential strategy for improving the clinical treatment of CRC.

Survival of patients with early-stage cervical cancer after sentinel lymph node biopsy without systematic pelvic lymphadenectomy: Primary endpoint outcome of the SENTIX prospective, single-arm, international trial (CEEGOG CX-01; ENGOT-CX2)

Survival of patients with early-stage cervical cancer after sentinel lymph node biopsy without systematic pelvic lymphadenectomy: Primary endpoint outcome of the SENTIX prospective, single-arm, international trial (CEEGOG CX-01; ENGOT-CX2)

Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre study

We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p=0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p=0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p=0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p=0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p=0.019). The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

CA-125 KELIM score predicts progression-free and overall survival in patients with epithelial ovarian cancer undergoing HIPEC at time of interval cytoreductive surgery

CA-125 KELIM score predicts progression-free and overall survival in patients with epithelial ovarian cancer undergoing HIPEC at time of interval cytoreductive surgery

Disease-free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant therapy

Disease-free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant therapy

GUCA2A dysregulation as a promising biomarker for accurate diagnosis and prognosis of colorectal cancer

Colorectal cancer is a leading cause of global mortality and presents a significant barrier to improving life expectancy. The primary objective of this study was to discern a unique differentially expressed gene (DEG) that exhibits a strong association with colorectal cancer. By achieving this goal, the research aims to contribute valuable insights to the field of translational medicine. We performed analysis of colorectal cancer microarray and the TCGA colon adenoma carcinoma (COAD) datasets to identify DEGs associated with COAD and common DEGs were selected. Furthermore, a pan-cancer analysis encompassing 33 different cancer types was performed to identify differential genes significantly expressed only in COAD. Then, comprehensively in-silico analysis including gene set enrichment analysis, constructing Protein–Protein interaction, co-expression, and competing endogenous RNA (ceRNA) networks, investigating the correlation between tumor-immune signatures in distinct tumor microenvironment and also the potential interactions between the identified gene and various drugs was executed. Further, the candidate gene was experimentally validated in tumoral colorectal tissues and colorectal adenomatous polyps by qRael-Time PCR. GUCA2A emerged as a significant DEG specific to colorectal cancer (|log2FC|> 1 and adjusted q-value < 0.05). Importantly, GUCA2A exhibited excellent diagnostic performance for COAD, with a 99.6% and 78% area under the curve (AUC) based on TCGA-COAD and colon cancer patients. In addition, GUCA2A expression in adenomatous polyps equal to or larger than 5 mm was significantly lower compared to smaller than 5 mm. Moreover, low expression of GUCA2A significantly impacted overall patient survival. Significant correlations were observed between tumor-immune signatures and GUCA2A expression. The ceRNA constructed included GUCA2A, 8 shared miRNAs, and 61 circRNAs. This study identifies GUCA2A as a promising prognostic and diagnostic biomarker for colorectal cancer. Further investigations are warranted to explore the potential of GUCA2A as a therapeutic biomarker.

Chimeric protein EWS::FLI1 drives cell proliferation in Ewing Sarcoma via aberrant expression of KCNN1/SK1 and dysregulation of calcium signaling.

Ewing sarcoma (ES) is characterized by EWS::FLI1 or EWS::ERG fusion proteins. Knowing that ion channels are involved in tumorigenesis, this work aimed to study the involvement of the KCNN1 gene, which encodes the SK1 potassium channel, in ES development. Bioinformatics analyses from databases were used to study KCNN1 expression in patients and cell lines. Molecular approaches and in vitro assays were used to study the transcriptional regulation of KCNN1 and its involvement in the regulation of ES cell proliferation. KCNN1 is overexpressed in ES patient biopsies, and its expression is inversely correlated with patient survival. EWS::FLI1, like EWS::ERG, promotes KCNN1 and SK1 expression, binding to GGAA microsatellites near the promoter of KCNN1 isoforms. KCNN1 is involved in the regulation of ES cell proliferation, with its silencing being associated with a slowing of the cell cycle, and its expression modulates membrane potential and therefore calcium flux. These results highlight that KCNN1 is a direct target of EWS::FLI1 and EWS::ERG and demonstrate that KCNN1 is involved in the regulation of intracellular calcium activity and ES cell proliferation, making it a promising therapeutic target in ES.

Is it necessary to diagnose and correct vitamin D deficiency in malignant neoplasms? Analytical review

BACKGROUND: Although the critical role of vitamin D in mineral homeostasis regulation is widely recognized, the global prevalence of vitamin D deficiency is exceedingly high. The substantial number of population-based studies that examine the correlation between the concentration of circulating vitamin D levels and the risk of developing cancer may be attributed to the growing interest of researchers in this vitamin as a suppressor of proliferating epithelial cells. However, the data collected are contradictory. AIM: To ascertain the necessity of diagnosing and rectifying vitamin D deficiency in cancer patients. MATERIALS AND METHODS: The keywords “vitamin D,” “vitamin D deficiency,” “cancer,” and “survival” were employed to identify publications in the e-Library, PubMed, and ScienceDirect databases from January 2014 to January 2024. Based on the data obtained, an analytical review of the literature was conducted. RESULTS: The global prevalence of vitamin D deficiency, including among cancer patients, is exceedingly high and does not vary by sex, age, or ethnicity. Decreased serum vitamin D levels are linked to an elevated incidence of colorectal cancer, breast cancer, melanoma, prostate, and pancreatic cancer. Addressing vitamin D deficiency helped mitigate the risk of developing breast cancer. Data on the effect of vitamin D deficiency and its correction on patient survival are inconsistent. CONCLUSION: Currently, there is no consensus regarding the impact of vitamin D supplementation on the incidence of diverse malignancies, as well as tumor-specific and overall survival. Additional research is required to address the necessity of diagnosing and correcting vitamin D deficiency.

The incidence and risk factors of post-transplant diabetes mellitus in living donor kidney transplantation patients: a retrospective study

BackgroundPost-transplant diabetes mellitus (PTDM) is a well-known complication of kidney transplantation that significantly impacts recipient morbidity and mortality. Over the recent years, the incidence of PTDM has increased considerably worldwide. Therefore, the primary purpose of this study was to evaluate the incidence and risk factors for PTDM in living donor kidney transplantation patients in Riyadh, Saudi Arabia.MethodsA retrospective cohort study was conducted at a tertiary transplant center in Riyadh, Saudi Arabia, and data were extracted between February 2016 and March 2022. Patients aged ≥ 18 years who underwent renal transplant with at least one year of post-transplant follow-up were included in the analysis, and their medical records were comprehensively reviewed. Patients < 18 years of age, history of diabetes mellitus, other organ transplants, or those who underwent transplantation outside the Kingdom of Saudi Arabia were excluded from the study.ResultsThe study included 247 living donor kidney transplant patients, with a mean age of 39.5 ± 14.6 years. 17.0% of the patients were diagnosed with PTDM. Patient age and fasting glucose levels at 6-months and 12-months after transplantation were found to be significant risk factors for the development of PTDM.ConclusionAn increased occurrence of PTDM emphasizes the importance of identifying high-risk patients prior to transplantation and implementing early interventions to prevent potential complications that could affect graft and patient survival.

Clinical Significance of HHLA2 as a Novel Therapeutic Target for Colorectal Cancer.

Colorectal cancer (CRC) is a high-indence malignance of the digestive system with a high mortality rate in the world. The results are desired to provide an important theoretical basis for discovering new therapeutic targets for CRC. The expression of human endogenous retrovirus-H-long terminal repeat association protein 2 (HHLA2) in human CRC was detected to explore its correlationship with clinicopathological features and prognosis of patients and its potential in treating CRC. Western blot was employed to detect HHLA2 expression in fresh tissues obtained from 6 CRC patients' excisions, including cancer, paracancer, and normal issues. Immunohistochemical staining was employed to determine HHLA2 expression in paraffin-embedded specimens of 139 patients with colorectal cancer, and its relationship with the clinicopathological profiles and survival was analyzed. Small interfering RNA (siRNA) targeting HHLA2 was used to transfect CRC cells to silent HHLA2. MTT, plate colony formation, cell scratch, and Transwell assay were conducted to observe the proliferation, migration, and invasion of CRC cells. HHLA2 protein was expressed in human colorectal cancer tissues, paracancer tissues and normal tissues, which was significantly upregulated in cancer tissues (P<0.01). HHLA2 expression level in CRC tissues showed a close correlationship with the invasion depth of the tumor (P=0.000), metastasis of regional lymph nodes (P=0.018), clinical stage (P=0.010), and patient survival (P=0.011). Correlation with gender (P=0.873), age (P=0.864), location of the tumor (P=0.768), degree of tumor differentiation (P=0.569) and distant metastasis (P=0.494) exhibited no significance. The survival time of CRC patients with high and low HHLA2 expression groups was 43.231 months and 55.649 months, respectively, with a statistical difference between the two groups (P=0.001). Silencing HHLA2 inhibited proliferation, migration and invasion of CRC cells significantly. HHLA2 is overexpressed in CRC tissues which is associated with poor prognosis of patients. HHLA2 might be recognized as a new candidate for adjuvant diagnosis and prognosis of CRC, as well as a promised new target for immunotherapy of CRC.