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TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer.

ABSTRACT: Platelets have been shown to promote the growth of tumors, including colorectal cancer. The RNA profile of tumor-educated platelets has the possibility for cancer diagnosis. We used RNA sequencing to identified the gene expression signature in platelets from colorectal cancer patients and healthy volunteers. We then verified the selected biomarkers from the RNA sequencing in a two-step case-control study using quantitative reverse-transcription polymerase chain reaction. We found that TIMP1 mRNA levels are higher in platelets from colorectal cancer patients than in platelets from healthy volunteers and patients with inflammatory bowel diseases. Additionally, TIMP1 mRNA expressed in platelets from colorectal cancer patients can be carried into colorectal cancer cells, where it promotes tumor growth in vivo and in vitro. These findings show that the TIMP1 mRNA in platelets is a potential independent diagnostic biomarker for colorectal cancer, and that platelets can carry RNAs into colorectal cancer cells to promote colorectal cancer development.

SUBMITTER: Yang L

PROVIDER: S-EPMC6834400 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer.

Yang Liu L Jiang Qian Q Li Dong-Zheng DZ Zhou Xin X Yu Dong-Sheng DS Zhong Jian J

Aging 20191022 20

Platelets have been shown to promote the growth of tumors, including colorectal cancer. The RNA profile of tumor-educated platelets has the possibility for cancer diagnosis. We used RNA sequencing to identified the gene expression signature in platelets from colorectal cancer patients and healthy volunteers. We then verified the selected biomarkers from the RNA sequencing in a two-step case-control study using quantitative reverse-transcription polymerase chain reaction. We found that TIMP1 mRNA ...[more]

PMID: 31639773

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Project description:BackgroundTo date, the role of programmed death ligand-1 (PD-L1) messenger RNA (mRNA) derived from tumor-educated platelets (TEPs) has not been well investigated in patients with advanced non-small cell lung cancer (NSCLC). A few reports have examined whether mRNA in TEPs can predict the clinical responses of patients with advanced NSCLC following immunotherapy. This study aimed to identify novel biomarkers to improve the clinical benefits and outcomes of NSCLC patients.MethodsAdvanced NSCLC patients receiving a combination of immunotherapy and chemotherapy, or immunotherapy alone as a first- or second-line treatment at the Fudan University Shanghai Cancer Center were enrolled in this study. All the patients had wild-type epidermal growth factor receptor/anaplastic lymphoma kinase. The patients were enrolled in clinical trials for immune checkpoint inhibitors (ICIs), including nivolumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab, and camrelizumab. Tumoral PD-L1 expression was tested by immunohistochemistry (PD-L1 22C3 pharmDx kit, Agilent, Santa Clara, CA, USA) in archived tissue samples, when available, to calculate the tumor proportion scores (TPSs). RNA and exosomal RNA of blood were isolated before immunotherapy using the Yunying RNA extraction kit (Yunying Medicine, Shanghai, China). The concentration and quality of the RNA was determined using a Qubit fluorometer (Life Technologies, Carlsbad, CA, USA). Finally, we analyzed the predictive value of TEP-derived PD-L1 mRNA expression and association with the level of the tumoral PD-L1 expression.ResultsIn total, 72 patients were enrolled in this study. Most of the patients were male (n=54, 75.0%), had adenocarcinoma (n=49, 68.1%). We found there was no significant correlation between the TEP-derived mRNA of PD-L1 and tumoral PD-L1 expression based on the results of the Pearson Correlation test (r=-0.19, P=0.233). Based on the median of PD-L1 mRNA, 72 patients were divided into a high PD-L1 group and a low PD-L1 group. We found that 19 patients (44.4%) responded to immunotherapy [partial response or progression-free survival (PFS) >6 months] in the high PD-L1 group, but only five patients (13.9%) responded to immunotherapy in the low PD-L1 group (P<0.01). The median PFS of the low PD-L1 group was lower than that of the high PD-L1 group (2.8 vs. 8.3 months, P<0.001). For the patients who were treated with immunotherapy alone (n=64), a similar PFS advantage was observed in the high PD-L1 group (2.8 vs. 8.0 months, P=0.002).ConclusionsThis article presented the first data on TEP-derived PD-L1 mRNA in advanced NSCLC patients following immunotherapy and showed the potential advantage of using it as the surrogate biomarker for predicting the PFS and overall survival of patients following immunotherapy.

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TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer.

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TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer.

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