ADAMTSL2 is a potential prognostic biomarker and immunotherapeutic target for colorectal cancer: Bioinformatic analysis and experimental verification.

The ADAMTS Like 2 (ADAMTSL2) mutation has been identified to be associated with different human genetic diseases. The role of ADAMTSL2 is unclear in colorectal cancer (CRC). The study investigated the expression of ADAMTSL2 in both pan cancer and CRC, using data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The study examined the correlation between ADAMTSL2 expression levels and clinical characteristics, as well as prognosis in CRC. The study explored potential regulatory networks involving ADAMTSL2, including its association with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB) / microsatellite instability (MSI), tumor stemness index (mRNAsi), and drug sensitivity in CRC. ADAMTSL2 expression was validated using GSE71187 and quantitative real-time PCR (qRT-PCR). ADAMTSL2 was aberrantly expressed in pan cancer and CRC. An increased level of ADAMTSL2 expression in patients with CRC was significantly associated with the pathologic N stage (p < 0.001), pathologic stage (p < 0.001), age (p < 0.001), histological type (p < 0.001), and neoplasm type (p = 0.001). The high expression of ADAMTSL2 in patients with CRC was found to be significantly associated with a poorer overall survival (OS) (HR: 1.67; 95% CI: 1.18-2.38; p = 0.004), progression-free survival (PFS) (HR: 1.55; 95% CI: 1.14-2.11; p = 0.005) and disease-specific survival (DSS) (HR: 1.83; 95% CI: 1.16-2.89; p = 0.010). The expression of ADAMTSL2 in patients with CRC (p = 0.009) was identified as an independent prognostic determinant. ADAMTSL2 was associated with extracellular matrix receptor (ECM-receptor) interaction, transforming growth factor ß (TGF-ß) signaling pathway, and more. ADAMTSL2 expression was correlated with immune infiltration, immune checkpoint genes, TMB / MSI and mRNAsi in CRC. ADAMTSL2 expression was significantly and negatively correlated with 1-BET-762, Trametinib, and WZ3105 in CRC. ADAMTSL2 was significantly upregulated in CRC cell lines. The high expression of ADAMTSL2 is significantly correlated with lower OS and immune infiltration of CRC. ADAMTSL2 may be a potential prognostic biomarker and immunotherapeutic target for CRC patients.

Preoperative C-reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer.

BACKGROUND: Increasing attention has been drawn the prognostic value of inflammatory indices for colorectal cancer (CRC). However, the prognostic value of the preoperative C-reactive protein to prealbumin ratio (CPAR) in CRC remains unclear. METHODS: A retrospective study was conducted with 794 patients who had CRC and underwent radical surgical resection. The predictive performance of the inflammatory indices was analyzed and compared using the area under the time-dependent receiver operating characteristic curve. A competing risk regression model and Cox proportional hazard model were used to analyze the effects of CPAR on disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: Patients with high CPAR (>7.25) had poor survival outcome. The CPAR had the best predictive performance among all inflammatory indices, and was significantly associated with several characteristics of tumor invasion, including histological grade, tumor stage, and tumor size. Multivariate analysis showed that high CPAR was independently associated with poor DFS (subdistribution hazard ratio = 2.28, 95% confidence interval [CI]: 1.74-2.82) and OS (hazard ratio = 1.78, 95% CI: 1.60-1.96). CONCLUSION: Preoperative CPAR assessment could serve as an effective and reliable tool for prognostic prediction in patients with resectable CRC.

Comparing Emotional Adjustment of Living-donor and Deceased-donor Kidney Transplant Patients.

Kidney transplantation is regarded as the best treatment option for patients with end-stage renal disease. However, living-donor recipients (LDRs) and deceased-donor recipients (DDRs) still face challenges in transplant-specific emotional adjustment post-transplantation. Research distinguishing emotional adjustment between transplant groups has been limited to Western settings, with little attention given to Asian populations. As such, documenting and comparing the emotional adjustment of LDRs and DDRs in an ethnically diverse Asian setting in Singapore and identifying factors associated with emotional adjustment are of interest. METHODS: One hundred eighty-two kidney transplant patients (106 LDRs and 76 DDRs) completed measures of generic distress (Depression, Anxiety, Stress Scale-21) and transplantation-specific emotional and behavioral outcomes (Transplant Effects Questionnaire). RESULTS: LDRs were significantly younger (P = 0.019) and had higher education levels (P = 0.007), higher personal income (P < 0.001), shorter dialysis vintage (P < .001), and higher estimated glomerular filtration rates (eGFRs) (P = 0.002) compared with DDRs. Generic symptoms of depression and stress were very low; however, 29.2% of LDRs and 19.7% of DDRs experienced moderate to severe symptoms of anxiety. Similarly, 83.0% of LDRs and 72.4% of DDRs reported high levels of transplant-specific worry. Multivariate models showed younger patients expressing greater generic distress, and transplant-specific worry (P < 0.01), despite higher eGFRs (P < 0.05). ANCOVA controlling for casemix differences showed that LDRs experienced higher feelings of guilt (P = 0.004) and greater willingness to disclosure (P = 0.041). CONCLUSIONS: Clinicians should be vigilant of younger kidney transplant patients who have greater risk of poorer emotional adjustment. Future interventions should target alleviating anxiety and transplant-specific worry.