The diffuse-type gastric cancer (DGC) is a subtype of gastric cancer with the worst prognosis and few treatment options. Here we present a dataset from 84 DGC patients, composed of a proteome of 11,340 gene products and mutation information of 274 cancer driver genes covering paired tumor and nearby tissue. DGC can be classified into three subtypes (PX1–3) based on the altered proteome alone. PX1 and PX2 exhibit dysregulation in the cell cycle and PX2 features an additional EMT process; PX3 is enriched in immune response proteins, has the worst survival, and is insensitive to chemotherapy. Data analysis revealed four major vulnerabilities in DGC that may be targeted for treatment, and allowed the nomination of potential immunotherapy targets for DGC patients, particularly for those in PX3. This dataset provides a rich resource for information and knowledge mining toward altered signaling pathways in DGC and demonstrates the benefit of proteomic analysis in cancer molecular subtyping.

/pdf/a-proteomic-landscape-of-diffuse-type-gastric-cancer-1wjdt2n5x5.pdf

A proteomic landscape of diffuse-type gastric cancer

Colorectal cancer (CRC) is one of the major health problems worldwide and is often diagnosed at late stage. There is growing body of evidence in early detection of this disease with novel screening modalities to reduce compliance and increase specificity of available methods. The aim of current review is to give an overview on currently available screening methods (e.g., fecal occult blood testing (FOBT), flexible sigmoidoscopy, and colonoscopy), with their own merits and disadvantages, and new genetic/epigenetic/protein markers, as novel screening modalities. There are several serum and fecal biomarkers that can predict CRC and polyps. Overall sensitivities for detection by fecal DNA markers ranged from 53 to 87 %, while a panel of serum protein markers provides a sensitivity/specificity up to 85 % for CRC. In particular, DNA methylation markers (e.g., SEPT9, SFRP2, and ALX4), circulating microRNAs (e.g., microRNA21), SNPs in microRNAs binding site (e.g., rs4596 located within a target region of the predicted miR-518a-5p and miR-527), protein markers (e.g., carcinoembryonic antigen, N-methyltransferase), or microsatellites instability in tumors with deficient mismatch repair of some genes are among the most interesting and promising biomarkers. Increasing evidence supports the use of combined fecal and serum biomarkers with sigmoidoscopy and colonoscopy screening in order to maximize the benefits and reduce the number of false-positive tests and patients undergoing invasive methods, which in turn could overcome the limitations of the current screening methods for early detection of CRC and adenomas.

Early detection of colorectal cancer: from conventional methods to novel biomarkers

Molecular Tests for Colorectal Cancer Screening

Several randomized controlled trials have shown that population-based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high-risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population-based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic-based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.25654

Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper.

Serum protein markers for early detection of ovarian cancer

The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumor-associated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor-associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme-linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY-CO-16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (> or =5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early-stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer-associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor-associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early-stage patients.

https://ir.nctu.edu.tw:443/bitstream/11536/5593/1/000274940200015.pdf

Multiple serological biomarkers for colorectal cancer detection

The purpose of this study was to examine the expression of phospholipid scramblase 1 (PLSCR1) in tumor tissues and plasma specimens of patients with colorectal cancer (CRC), as well as analyze its association with clinical parameters. The expression levels of PLSCR1 protein in 104 matched CRC and adjacent normal tissue sections and 50 pairs of CRC tissue blocks were determined by use of immunohistochemical and Western blot analyses, respectively. To evaluate the diagnostic potential of PLSCR1, the plasma levels of PLSCR1 were investigated in 111 additional subjects (59 CRC patients and 52 healthy controls) by Western blot. PLSCR1 was overexpressed in malignant adenocarcinoma tissues compared with normal colorectal mucosa (P < 0.001). In addition, the plasma level of PLSCR1 was not only significantly elevated in CRC patients compared with healthy individuals (P < 0.001), but it was also substantially increased in early stage CRC (P < 0.001). Importantly, the overall sensitivity and specificity of PLSCR1 for CRC detection were 80% and 59.6%, respectively. The area under the ROC curve of PLSCR1 for CRC diagnosis is 0.75, which increases to 0.8 if combined with the measurement of carcinoembryonic antigen. Univariate analysis with the Cox regression model revealed that elevated PLSCR1 expression indicated a poor prognosis for CRC. This study showed that PLSCR1 protein levels were significantly elevated in both the cancer tissue and plasma of CRC patients. Moreover, the plasma levels of PLSCR1 were significantly elevated in patients with early stage CRC compared with healthy individuals, suggesting that PLSCR1 might be used as a noninvasive serological diagnostic and prognostic biomarker for CRC.

https://ir.nctu.edu.tw:443/bitstream/11536/26102/1/000286708100008.pdf

Identification of Phospholipid Scramblase 1 as a Biomarker and Determination of Its Prognostic Value for Colorectal Cancer

Background: Annexins (ANXAs) belong to a superfamily of closely related calcium and membrane-binding proteins and are over-expressed in some carcinomas. The overexpression of ANXAs presumably induces an autoantibody response, but this has not been demonstrated for sera from colorectal cancer (CRC) patients. Study: We examined serum samples from 220 CRC patients and 216 healthy volunteers to evaluate the ANXA autoantibody response in patients by using an enzyme-linked immunosorbent assay with recombinant ANXA A4 as the antigen. Results: The sensitivity of the anti-ANXA response from CRC patient sera was about 85% and the specificity was about 61.6%. When a cut-off value of 5.0 ng/mL was chosen for carcinoembryonic antigen (CEA) in the same sera samples, the sensitivity and specificity values were 43.2% and 85.2%, respectively. Combined detection using ANXA autoantibodies and CEA produced better sensitivity (71.8%) and specificity (79.2%) compared with CEA sensitivity (43.2%) and anti-ANXA specificity (61.6%). The area under a receiver operating characteristic curve was 0.794 for ANXA autoantibodies, 0.666 for CEA, and 0.84 for both markers together. Importantly, in comparison to CEA (27.5% seropositivity), ANXA autoantibody showed a remarkable change (81.3% seropositivity) at the early stage of CRC. Conclusions: Measurement of ANXA autoantibody levels may provide an alternative detection indicator for CRC, particularly among early-stage patients.

Detection of annexin A autoantibodies in sera from colorectal cancer patients.

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Multiple serological biomarkers for colorectal cancer detection

Identification of Phospholipid Scramblase 1 as a Biomarker and Determination of Its Prognostic Value for Colorectal Cancer

Detection of annexin A autoantibodies in sera from colorectal cancer patients.