KSHV K15 genetic heterogeneity is associated with Kaposi sarcoma aggressiveness through modulation of the host inflammatory microenvironment.

KSHV K15 M-genotype is linked to increased Kaposi sarcoma severity through heightened inflammation and edema in patients from Xinjiang, China.

• Why it matters: Current risk assessments for Kaposi sarcoma rely on anatomical staging, which does not fully capture disease heterogeneity or biological differences. Understanding viral genetic factors could improve prognostic accuracy and treatment strategies.
• What they did: The study analyzed 156 patients, categorizing disease as localized or disseminated, and used causal mediation analysis to examine the relationship between K15 genotypes, inflammation, and clinical features. A prognostic nomogram was developed with six factors, showing superior discrimination compared to traditional staging.
• The result: The K15 M-genotype was independently associated with a hyper-inflammatory phenotype, mediating 29.0% of edema effects, and the model achieved a concordance index of 0.761, enabling better risk stratification and potential for biology-driven management.