Diabetes mellitus (DM) is the common comorbidity with lung cancer (LC), and metabolic disorders have been identified as significant contributors to the pathogenesis of both DM and LC. The causality between diabetes mellitus and lung cancer is still controversial. Hence, the causal effects of DM on the risk of LC was systemically investigated, and the mediating role of blood metabolites in this relationship was further explored.

This study utilized a comprehensive Mendelian randomization (MR) analysis to investigate the association between diabetes mellitus and lung cancer. The inverse variance weighted method was employed as the principle approach. MR Egger and weighted median were complementary calculations for MR assessment. A two-step MR analysis was performed to evaluate the mediating effects of blood metabolites as potential intermediate factors. Simultaneously, sensitivity analyses were performed to confirm the lack of horizontal pleiotropy and heterogeneity.

The two-sample MR analysis illustrated the overall effect of type 1 diabetes mellitus (T1DM) on lung squamous cell carcinoma (LUSC) (OR: 1.040, 95% CI: 1.010-1.072, p = 0.009). No causal connection was found between T2DM and the subtypes of lung cancer. Two-step MR identified two candidate mediators partially mediating the total effect of T1DM on LUSC, including glutamine conjugate of C6H10O2 levels (17.22%) and 2-hydroxyoctanoate levels (5.85%).

Our findings supported a potentially causal effect of T1DM against LUSC, and shed light on the importance of metabolites as risk factors in understanding this relationship.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

This article is a comprehensive study based on research on the connection between diabetes mellitus (DM) and prostate cancer (PCa). It investigates the potential role of DM as an independent risk factor for PCa, delving into the biological links, including insulin resistance and hormonal changes. The paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing causality. It emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa, and proposes future research directions for further under-standing the DM - PCa relationship.

According to the preclinical data, sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) may exert anticancer effects. Here, we clarified the cancer-specific mortality (primary outcome) and all-cause mortality (secondary outcome) of SGLT2is and their dose-dependency in patients with cancer undergoing standard curative treatments.

We analyzed data from patients with type 2 diabetes mellitus (T2DM) diagnosed with cancer between January 1, 2016, and December 31, 2018, enrolled from the Taiwan Cancer Registry database. Kaplan-Meier method was used to estimate all-cause mortality and cancer-specific mortality, comparing survival curves between SGLT2i users and nonusers using the stratified log-rank test. Cox proportional hazards regression was conducted to identify independent predictors for all-cause and cancer-specific mortality among the covariates.

We performed 1:2 propensity score matching of our data, which yielded a final cohort of 50,133 patients with cancer; of them, 16,711 and 33,422 were in the SGLT2i user and nonuser groups, respectively. The adjusted hazard ratio (aHR) for cancer-specific and all-cause mortality in SGLT2i users compared with nonusers was 0.21 (95 % confidence interval [CI]: 0.20-0.22) and 0.22 (95 % CI: 0.21-0.23). We divided the patients into four subgroups stratified by quartiles (Q) of cumulative defined daily doses per year (cDDDs), and all-cause and cancer-specific mortality was noted to significantly decrease with increases in dosage (from Q1 to Q4 cDDDs) in SGLT2i users compared with in nonusers (P < 0.001).

SGLT2is increase overall survival and cancer-specific survival in patients with cancer in a dose-dependent manner.

Diabetes is a common comorbidity in patients with early-stage non-small cell lung cancer (NSCLC), a growing population due to increased LC screening. However, it is unknown if diabetes is associated with less aggressive NSCLC treatment and worse NSCLC outcomes. This study aimed to investigate treatment patterns and outcomes of older patients with Stage I NSCLC and diabetes.

Using national cancer registry data linked to Medicare, we identified patients ≥65 years old with Stage I NSCLC. Patients were categorized as having no diabetes, diabetes without severe complications (DM-c), or diabetes with ≥1 severe complication (DM + c). We used multinomial logistic regression to assess the association of diabetes and NSCLC treatment. The association of diabetes category with NSCLC and non-NSCLC survival was analyzed with Fine-Grey competing-risks regression.

In 25,358 patients (75% no diabetes, 12% DM-c and 13% had DM + c), adjusted analyses showed that DM-c and DM + c were associated with increased odds of receiving limited resection rather than lobectomy (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.07-1.37 and OR 1.42, 95% CI 1.26-1.59, respectively). Competing risk regression showed diabetes was associated with increased risk of non-NSCLC death (DM-c hazard ratio [HR] 1.16, 95% CI: 1.08-1.25, DM + c HR 1.49, 95% CI: 1.40-1.59), but not NSCLC-specific death.

This study uncovers critical information on how diabetes is associated with less aggressive early-stage NSCLC care in older patients. This study also confirms that diabetes increases death from non-lung cancer causes and managing comorbidities is crucial to improving outcomes in older early-stage NSCLC survivors.

Lung cancer, including both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), remains one of the most aggressive types of cancer, and the prognosis for individuals diagnosed with this neoplasm has, for the most part, been insufficient [...].

Radioresistance is a major obstacle for the successful therapy of many cancers, including non-small cell lung cancer (NSCLC). To elucidate the mechanism of radioresistance of NSCLC cells and to identify key molecules conferring radioresistance, the radioresistant subclones of p53 wild-type A549 and p53-deficient H1299 cell cultures were established. The transcriptional changes between parental and radioresistant NSCLC cells were investigated by RNA-seq. In total, expression levels of 36,596 genes were measured. Changes in the activation of intracellular molecular pathways of cells surviving irradiation relative to parental cells were quantified using the Oncobox bioinformatics platform. Following 30 rounds of 2 Gy irradiation, a total of 322 genes were differentially expressed between p53 wild-type radioresistant A549IR and parental A549 cells. For the p53-deficient (H1299) NSCLC cells, the parental and irradiated populations differed in the expression of 1628 genes and 1616 pathways. The expression of genes associated with radioresistance reflects the complex biological processes involved in clinical cancer cell eradication and might serve as a potential biomarker and therapeutic target for NSCLC treatment.