Fig. 4: Visualization and prognostic value of SSTR2 expression in NPC patients.

a Visualization of SSTR2 expression by ⁶⁸Ga-DOTA-TATE PET-CT imaging (clinical characteristics and SSTR2 status of NPC patients undergoing ⁶⁸Ga-DOTA-TATE PET-CT imaging are shown in Supplementary Table 4). b Correlation of SSTR2 expression with in vivo uptake of ⁶⁸Ga-DOTA-TATE. SSTR2 IHC score shows significant positive correlation to SUVmax of biopsied lesion. (black circles: biopsied lesions, n = 12; Spearman’s correlation coefficient: R_s = 0.65; p = 0.023). d SSTR2 expression status remains prognostic independent of EBV status, age, and primary tumor (T), lymph node (N), and metastasis (M) staging. n.s not significant; *p < 0.05; **p < 0.01; ***p < 0.001. Vertical lines display the hazard ratio estimate, horizontal lines display the 95% confidence interval. e Proposed model of NPC oncogenesis and cancer progression involving EBV and SSTR2 expression. In the multistep carcinogenesis of NPC, inactivation of tumor suppressor genes is believed to occur prior to EBV infection and to be induced by dietary carcinogens and other environmental factors. Infection of nasopharyngeal cells with EBV and establishment of a latent infection probably occurs at a late stage in the acquisition of the malignant phenotype. Genetic alterations identified in premalignant nasopharyngeal epithelium may play crucial roles to support stable EBV infection. Once a premalignant cell has been infected by EBV, it appears to rapidly evolve towards an invasive tumor, with the stage of EBV-positive in situ carcinoma being very transient. SSTR2 expression is acquired following the onset of latent EBV infection by LMP1 expression via NF-ĸB signaling. On the basis of this tentative scenario, pharmacological agonists of SSTR2 are expected to provide the maximal benefit for three types of indications: (1) as part of the initial curative treatment of the primary tumors, (2) as part of adjuvant treatment following clinical remission of the primary tumor; (3) with a prophylactic intent for subjects at risk of NPC manifested by EBV serological changes and/or increasing circulating EBV DNA load. Source Data are provided as a Source data file.