Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival

Abstract

IntroductionWe studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients.Patients and methodsT2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P < 0.05 were considered statistically significant.ResultsTwo-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) (P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival (P < 0.05). At multivariate analysis, age (≥65 vs. <65 years), response to first-line chemotherapy (DC vs. no DC), and concomitant presence of T2D, BMI, and HT (HR: 4.56; 95% CI: 2.40–8.67; P = 0.0217) emerged as independent prognostic variables. P53 was mutated in 31/53 analyzed cases (60.4%). The most frequent gene variants were p.Arg175His and p.Cys135Tyr. High BMI (>25 kg/m2) associated with occurrence of p53 mutations (P < 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43–7.23; P = 0.0047).ConclusionDiabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence.

Exploration and validation of the Ki67, Her-2, and mutant P53 protein-based risk model, nomogram and lymph node metastasis model for predicting colorectal cancer progression and prognosis

“…One study showed that MutP53 protein expression is positively correlated with tumor diameter (29). Another study showed that patients with high MutP53 proteins expression have a significantly shorter survival time than patients with high expression of the wild-type P53 protein (30). Moreover, patients with CRC with dMMR have significantly lower MutP53 proteins expression than patients with pMMR (31).…”

Clinical Outcome of Colorectal Cancer Patients with Concomitant Hypertension: A Systematic Review and Meta-Analysis

“…The database search yielded 802 studies for screening (PubMed (n = 425), Embase (n = 124), Web sciences (n = 107), Scopus (n = 87), Cochrane Library (n = 34), CINAHL (n = 25)), of which 298 abstracts were identified as potentially eligible and retrieved for full-text review. Finally, 16 articles met the eligibility criteria and were included in this systematic review and meta-analysis [3,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The detailed PRISMA flowchart for study screening and selection is presented in Figure 1.…”

“…All the included articles were published between 2009 and 2023 and originated from eight countries. Among the 16 articles included in this systematic review and meta-analysis, 15 were retrospective [3,[17][18][19][20][21][22][24][25][26][27][28][29][30][31], and only 1 was a prospective study [23]. The sample size of the included articles varied from 45 to 750 participants, with a slightly higher proportion of male patients (58%).…”

An ensemble WideResNet learning-based approach for classification of multi-class colorectal cancer tissue types in histology images

“…Clinical outcomes, however, can differ significantly between patients with resectable diseases. Tumor symptoms encompass several factors such as type 2 diabetes, nutritional deficiencies, diabetes, obesity, and smoking, which have been found to be associated with reduced odds of survival [3,4]. CRC typically recurs in 60 to 80% of cases and 95% within four years of resection [4,5].…”

“…Tumor symptoms encompass several factors such as type 2 diabetes, nutritional deficiencies, diabetes, obesity, and smoking, which have been found to be associated with reduced odds of survival [3,4]. CRC typically recurs in 60 to 80% of cases and 95% within four years of resection [4,5]. Colon malignancies are frequently identified by the utilization of needle biopsy or fine needle aspiration (FNA) techniques [5,6].…”