The Prognostic Value of Tyrosine Kinase SRC Expression in Locally Advanced Rectal Cancer

Abstract

The cellular sarcoma gene (SRC) is a proto-oncogene encoding for a tyrosine kinase. SRC expression was determined in locally advanced rectal adenocarcinoma tissue from pretreatment biopsies and resection specimens. The expression level was correlated with clinicopathological parameters to evaluate the predictive and prognostic capacity.For this monocentric analysis 186 patients with locally advanced rectal cancer (median: 63.7 years; 130 men (69.9%), 56 women (30.1%)) were included. Patients with a carcinoma of the upper third of the rectum were treated with primary tumor resection (n=27; 14.5%). All other patients received a preoperative chemoradiotherapy (CRT) with 50.4 Gy and concomitant 5-fluorouracil (5-FU) or 5-FU+oxaliplatin followed by postoperative chemotherapy with 5-FU or 5-FU+oxaliplatin. SRC expression was determined with immunohistochemical staining from pretreatment biopsies (n=152) and residual tumor tissue from the resection specimens (n=163). The results were correlated with clinicopathological parameters and long-term follow-up.The expression of SRC was determined in pretherapeutic biopsies (mean H-Score: 229) and resection specimens (mean H-Score: 254). High SRC expression in pretherapeutic tumor samples significantly correlated with a negative postoperative nodal status (p=0.005). Furthermore an increased protein expression in residual tumor tissue was associated with fewer distant metastases (p=0.04). The overexpression of SRC in pretreatment tumor biopsies showed also a trend for a longer cancer-specific survival (CSS; p=0.05) and fewer local relapses (p=0.06) during long-term follow-up.High SRC expression in rectal cancer seems to be associated with a better long-term outcome. This finding could help in the future to stratify patients for a recurrence risk adapted postoperative treatment.

Integrated bioinformatics and network pharmacology to explore the therapeutic target and molecular mechanisms of Taxus chinensis against non-small cell lung cancer

“…[31] SRC plays an essential role in promoting cancer progression, metastasis, and drug resistance in NSCLC by interacting with different receptor tyrosine kinases, such as epidermal growth factor receptor, and participating in intracellular signaling pathways, such as PI3K/Akt and MAPK/ ERK. [32][33][34] The expression or kinase activity of SRC is increased in human NSCLC cells and is associated with a poor prognosis. [35] Inhibition of SRC helps overcome the resistance of NSCLC cells to targeted therapies and effectively improves their sensitivity to radiotherapy.…”

Magnet-Resonanz-Tomographie-Diagnostik beim fortgeschrittenen Rektumkarzinom (UICC II bis IV) vor und nach neoadjuvanter Radio-/Chemotherapie - Stellenwert aus chirurgischer Sicht

“…Unter Hinzunahme von Oxaliplatin zur postoperativen CTx wurde das 3 Jahre DFS gegenüber der Kontrollgruppe verbessert (p=0,03) (Rödel et al 2015, Rödel et al 2012. Zudem erwiesen sich die chirurgische TME-Qualität und die RCT-induzierte Tumorregression als unabhängige, prognostische Faktoren (Rödel et al 2005, Fokas et al 2014, Fokas et al 2015, Fokas et al 2017 , Liersch et al 2006a, Liersch et al 2009a, Liersch et al 2010, Poschau et al 2015, Rühlmann et al 2017, Marks et al 2018. Limitiert infolgedessen der Chirurg im interdisziplinären Konsens seine initial geplante OP-Strategie, so bedarf es einer weiteren, engmaschigen Verlaufskontrolle der Tumorsituation per MRT (z. B.…”

“…Insgesamt hat sich die präoperative Multimodaltherapie beim fortgeschrittenen Rektumkarzinom etabliert und ermöglicht dem Patienten Überlebensvorteile (Babaei et al 2017). Ob aufgrund eines ymrCR Befundes tatsächlich ganz oder zumindest partiell auf die onkologische Tumorresektion verzichtet werden kann, muss in klinischen Studien Evidenz-basiert geklärt werden (Appelt et al 2015, Sprenger et al 2017.…”