Selected Articles from This Issue

It is unclear how plasma 25-hydroxyvitamin D (25[OH]D) is associated with stage III colon cancer outcomes and if such association is mediated by circulating inflammatory cytokines. Using data from a phase III randomized clinical trial, Wang and colleagues found higher 25(OH)D levels were associated with decreased cancer recurrence and improved survival in a possible U-shaped pattern. The protective effect of 25(OH)D was independent of circulating CRP and IL-6 but was marginally mediated by sTNF-R2. Plasma 25(OH)D could be a good prognostic predictor for survival of stage III colon cancer and more studies are suggested to determine whether vitamin D supplementation improves outcomes.

The immune checkpoint receptor (ICR) TIGIT has recently been suggested to be involved in pancreatic cancer-immune evasion. Heiduk and colleagues studied single- and co-expression of TIGIT and PD-1 by intratumoral T cells in pancreatic ductal adenocarcinoma (PDAC) and identified distinct T-cell subpopulations. PD-1⁺TIGIT-conventional CD4⁺ T cells had a highly proinflammatory, potentially antitumorigenic phenotype, which was associated with improved patient survival. In contrast, TIGIT expression marked exhausted and antiinflammatory T cells, underscoring its relevance for future immunotherapeutic strategies. Additionally, ICR expression in the blood had a substantial prognostic value, suggesting relevance of blood immune phenotyping as a cost-effective, minimally invasive method for PDAC patient stratification.

Compared with most other pediatric kidney cancers, Wilms tumor (WT) with diffuse anaplasia (DA) is associated with poor event-free survival. How DA emerges in WTs has remained unclear. Rastegar and colleagues explored the emergence of DA by spatially mapping WTs, followed by genomic profiling and phylogenetic reconstruction. They found that WT DA had uniformly complex phylogenetic trees with TP53 alterations being the starting point of saltatory evolution, with cascades of copy number aberrations. They further showed that sampling across macroscopic tumor nodules could be used to efficiently survey the genetic variation in WT DA for purposes of precision medicine.

RAS mutations occur across the spectrum of thyroid neoplasms. To evaluate how additional genetic events affecting key genes modify prognosis in RAS-mutant thyroid cancers, Bikas and colleagues performed a clinical-genomic analysis using NGS data of differentiated, poorly differentiated, and anaplastic thyroid cancers (DTC, PDTC, ATC). Out of 78 tumors included, all ATCs had an additional mutation and poor prognosis. DTCs with additional mutations were found to have a more aggressive course, and increased mortality compared to RAS-only DTC. These data can explain diversity of RAS-mutated thyroid neoplasia and support genomic profiling of DTCs to inform prognosis and clinical decision-making.