Low Mmp 9 and VEGF levels predict good oncologic outcome in mid and low rectal cancer patients with neoadjuvant chemoradiation

Abstract

BackgroundThe aim of this study was to evaluate apoptotic (Bcl-2, Bax expression, caspase-3 activity, and cytochrome-c) and angiogenic (MMP-9 levels and VEGF expression) markers in operable rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Understanding these factors will facilitate the identification of potential pathological responders before treatment, leading to better local control and survival rates.MethodsBetween March 2006 and March 2008, 29 patients withTNM Stage III (cT3 N+) mid or low rectal cancer were included in this study. Our sample consisted of 17 males (58.6%) and 12 females (41.4%). The median age was 60 years (range 24-88 years). Biopsy samples were taken from different portions of the tumors using flexible endoscopy before neoadjuvant CRT. Preoperatively, all patients received radiation (45-50.4 gray (Gy) in 25 cycles with concurrent 5-florouracil (5-FU) chemotherapy.ResultsA complete response was observed in 7 of 29 patients (24%). Bax staining was negative in 1 of the 7 patients (14%) in the pathological complete response (PCR) group and in 18 of the 22 patients (82%) in the no pathological complete response (noPCR) group (p = 0.001). MMP-9 and VEGF levels were higher in the noPCR group than the PCR group (p = 0.04, p = 0.05 respectively). No statistically significant differences were found between VEGF and MMP-9 levels in nodal downstaging. No statistically significant relationships were found between the other apoptotic factors (Bcl 2, cytochrome-c, and caspase-3 activity) and pathological response rate (p > 0.05).ConclusionIn neoadjuvant CRT patients, high levels of Bax expression and low levels of VEGF and MMP-9 expression on preoperative biopsies indicate that the patient will potentially be a good pathological responder.

Lentivirus-Mediated Gene Silencing of Lymphocyte Function-Associated Antigen 1 Inhibits Apoptosis of Hippocampal Neurons in Rats with Acute Cerebral Ischemia After Cerebral Lymphatic Blockage

“…The level of LFA-1 was reported to be increased in mice following the knockdown of MMP-9, suggesting MMP-9 played a regulatory role in LFA-1 [24], for which our results provided further evidence by Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry indicating that both silencing and overexpression of LFA-1 could reduce and increase the level of MMP-9. Bcl-2, Bax, and Caspase-3, are all apoptotic markers, with MMP-9 acting an angiogenic marker [25]. The Bcl-2 family of proteins could regulate apoptosis [26].…”

Radio-responsive tumors exhibit greater intratumoral immune activity than nonresponsive tumors

“…The majority of the work addressing this issue focuses on predictive factors present in tumors before treatment 2, 4-6 . Consequently, a list of genes that may discriminate responders versus non-responders has been identified and includes genes associated with cell cycle, apoptosis, DNA repair, and survival 2, 3, 5-7 . However, little work has addressed whether changes occur directly within responder or non-responder tumors shortly after RT, and if these modifications correlate with outcome.…”

“…2,[4][5][6] Consequently, a list of genes that may discriminate responders versus nonresponders has been identified and includes genes associated with cell cycle, apoptosis, DNA repair and survival. 2,3,[5][6][7] However, little work has addressed whether changes occur directly within responder or nonresponder tumors shortly after RT, and if these modifications correlate with outcome. In other words, what is lacking is a thorough understanding of the mechanism that governs either a positive or negative outcome in response to radiotherapy.…”

Network Mapping of Molecular Biomarkers Influencing Radiation Response in Rectal Cancer

“…Apoptosis Apoptotic index, 12,29 Bax, 14,16,30 BIRC5, [10][11][12][13] caspase-8, 31 hPEBP4, 32,33 M30, 34 MIB1, 15 p53, [14][15][16][17][18][19] PDCD4, 35 phospho-Akt, 21 XIAP, 36 YKL-40, 27 CD34, 37 calsenilin, 28 15 phospho-Akt, 21 thymidine phosphorylase, 37 VEGF, 15,16,24,37,39,[42][43][44][45] YKL-40 27 51.71429 18.94737…”

“…Response to hypoxia HIF-1, 39 HIF-1a, 14 CA9, 40 c-met, 27 CXCL10, 41 phospho-Akt, 21 thymidine phosphorylase, 37 VEGF, 15,16,24,37,39,[42][43][44][45] YKL-40 27 44.28571 16.47059 Response to DNA damage stimulus MSH2, 15 MTHFR 677T-1298A, 49 BIRC5, 10-13 hOGG1-1245C > G, 48 MTFHR-677C > T, 48 NEIL2, 11 NF-kB, 10,51 p53, [14][15][16][17][18][19] XRCC2 52 55.42857 43.47826 DNA repair MSH2, 15 BIRC5, [10][11][12][13] hOGG1-1245C > G, 48 MTFHR-677C > T, 48 NEIL2, 11 p53, 14-19 XRCC2 52 48 48…”