SAMHD1 as a prognostic and predictive biomarker in stage II colorectal cancer: A multicenter cohort study

Abstract

BackgroundThe identification of high-risk population patients is key to the personalized treatment options for the stage II colorectal cancers. The use of proteomics in the prognosis of patients with stage II colorectal cancer remains unclear.MethodsUsing quantitative proteomics, we analyzed proteins that are differentially expressed in the tumor and adjacent normal tissues of 11 paired colorectal cancer patients with and without recurrence selected by a nested case-control design. Of the 21 identified proteins, we selected one candidate protein. The association of the corresponding gene of the selected protein with overall survival (OS) and adjuvant chemotherapy was analyzed using two independent cohorts of patients with stages II colorectal cancer.ResultsSterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) was selected as the candidate biomarker. A group of 124 patients (12.5%) were stratified into SAMHD1-high subgroup. The 5-year OS rate of SAMHD1-high patients was lower than that of SAMHD1-low patients with stage II colorectal cancer (discovery cohort: hazard ratio [HR] = 2.89, 95% confidence interval [CI], 1.17-7.18, P = 0.016; validation cohort: HR = 2.25, 95% CI, 1.17-4.34, P = 0.013). The Cox multivariate analysis yielded similar results. In a pooled database, the 5-year OS rate was significantly different between patients with and without adjuvant chemotherapy among stage II SAMHD1-low tumors than in patients with stage II SAMHD1-high tumors (88% vs. 77%, P = 0.032).ConclusionsSAMHD1-high expression could help in identifying patients with stage II colorectal cancer with poor prognosis and less benefit from adjuvant chemotherapy.

SAMHD1 silencing cooperates with radiotherapy to enhance anti-tumor immunity through IFI16-STING pathway in lung adenocarcinoma

“…The functional consequences of SAMHD1 in cancer development and treatment still require further researches. In the colorectal cancer, high expression SAMHD1 correlated with metastasis [ 30 ] and indicated poor prognosis of stage II patients [ 31 ]. Consistent with our results, Eudald Felip et al found that low expression of SAMHD1 was associated with a positive prognosis in breast, ovarian and non-small cell lung cancer patients [ 32 ].…”

ZNF326 as a potential prognostic and predictive biomarker in stage II colorectal cancer

“…ZNF326 was selected as a candidate biomarker based on previous proteomics analyses and literature reviews ( 24 ). Briefly, we established a Yunnan CRC cohort comprising stage I–III CRC patients at Yunnan Cancer Hospital between December 2010 and February 2019.…”

“…Compared with genomics, the verification and interpretation provided by proteomics are closer to phenotype, and virtually all existing drug targets are proteins ( 22 , 23 ). We have previously reported that at least 5 proteins, including the ZNF326 , varied on the tumor tissues between the recurrence and non-recurrence CRC patients through a nested case-control cohort that combined the proteomics ( 24 ). However, the prognostic value of ZNF326 in stage II CRC patients is unclear.…”