Abstract
Recurrence of colorectal cancer (CRC) following a potentially curative resection is a challenging clinical problem. Matrix metalloproteinase-7 (MMP-7) is over-expressed by CRC cells and supposed to play a major role in CRC cell diffusion and metastasis. MMP-7 RNA expression was assessed by real-time PCR using specific primers in peritoneal washing fluid obtained during surgical procedure. After surgery, patients underwent a regular follow up for assessing recurrence. transcripts for MMP-7 were detected in 31/57 samples (54%). Patients were followed-up (range 20-48 months) for recurrence prevention. Recurrence was diagnosed in 6 out of 55 patients (11%) and two patients eventually died because of this. Notably, all the six patients who had relapsed were positive for MMP-7. Sensitivity and specificity of the test were 100% and 49% respectively. Data from patients have also been corroborated by computational approaches. Public available coloncarcinoma datasets have been employed to confirm MMP7 clinical impact on the disease. Interestingly, MMP-7 expression appeared correlated to Tgfb-1, and correlation of the two factors represented a poor prognostic factor. This study proposes positivity of MMP-7 in peritoneal cavity as a novel biomarker for predicting disease recurrence in patients with CRC.
Highlights
Colorectal cancer (CRC) is the second most commonly diagnosed solid malignancy in women and the third most common in men worldwide, accounting for over 600,000 deaths in 2008 [1–9]
Adenocarcinoma represents the vast majority of CRC and 70% of all malignant tumors of gastrointestinal tract
The first 10 lavages were needed to set the methodology whereas the subsequent 47 samples were the object of the study and used to assess Matrix metalloproteinase-7 (MMP-7) expression by real-time polymerase chain reaction (PCR)
Summary
Colorectal cancer (CRC) is the second most commonly diagnosed solid malignancy in women and the third most common in men worldwide, accounting for over 600,000 deaths in 2008 [1–9]. In the United States, CRC is the second leading cause of cancer death accounting for approximately 9% of deaths related to cancer overall [10]. Detection of tumor cells within the peritoneal cavity at the time of surgery has been proposed to identify patients with poorer outcome overall. Positive free cancer cells in the peritoneal cavity (IFTC) can be detected in a variable percentage of CRC patients at the time of surgery [22, 23]. The presence of IFTC is not currently used as a prognostic factor due to the heterogeneity in sampling and analysis among different studies. This is likely due to the lack of a standard method that allows IFTC identification with sufficient accuracy
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