Abstract
Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is a standard therapy for locally advanced rectal cancer (LARC). The aim of this study was to assess the expression of GOLPH3 (Golgi phosphoprotein 3), a newly found oncogene, in LARC as well as its relationship with nCRT sensitivity and prognosis. We retrospectively analyzed 148 LARC cases receiving nCRT and total mesorectal excision (TME). Immunohistochemistry was used to assess GOLPH3 and mTOR (mammalian target of rapamycin) in tumor tissues. Then, the associations of GOLPH3 with pathological characteristics and prognosis of rectal cancer were assessed. The 148 cases included 77 with high GOLPH3 expression (52.03%), which was associated with tumor invasive depth and lymphatic metastasis. Cases with high GOLPH3 expression had 2.58 and 2.71 fold higher local relapse and distant metastasis rates compared with the low expression group. Correlation analyses showed that GOLPH3 was an independent indicator for judging tumor down-staging and postoperative TRG (tumor regression grade), indicating it could predict nCRT sensitivity. In addition, GOLPH3 expression was associated with mTOR levels. Multiple-factor analysis indicated that GOLPH3 was an independent prognosis indicator for 5 year-DFS (disease free survival) and OS (overall survival) in LARC. These results reveal that GOLPH3 is an independent predictive factor for nCRT sensitivity and prognosis in LARC, with a mechanism related to mTOR.
Highlights
Morbidity and mortality of colorectal cancer is steadily increasing, which severely threatens human health
These results reveal that Golgi phosphoprotein 3 (GOLPH3) is an independent predictive factor for Neoadjuvant chemoradiotherapy (nCRT) sensitivity and prognosis in locally advanced rectal cancer (LARC), with a mechanism related to mTOR
This is the first study to assess the associations of the new oncogene-GOLPH3 and nCRT in rectal cancer
Summary
Morbidity and mortality of colorectal cancer is steadily increasing, which severely threatens human health. This tumor is the third cause of death from all malignancies [1]. In the past 30 years, therapies for rectal cancer have gained great improvements. Total mesorectal excision (TME) and neoadjuvant chemoradiotherapy (nCRT) greatly decrease local relapse rate and increase patient survival, and are considered standard therapies for locally advanced rectal cancer (LARC) [2,3,4]. Sensitivity genes should be urgently identified to predict the effect of nCRT on rectal cancer.
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