Combination of high anti-SKI and low anti-TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma.

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s-SKI-Abs and s-TMED5-Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s-SKI-Ab-positive and s-TMED5-Ab-negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s-SKI-Ab-positive and s-TMED5-Ab-negative cases showed an even clearer difference in overall survival as compared with that of s-SKI-Ab-negative and s-TMED5-Ab-positive cases. The s-SKI-Ab and s-TMED5-Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.

The combination of positive anti­WDR1 antibodies with negative anti­CFL1 antibodies in serum is a poor prognostic factor for patients with esophageal carcinoma.

WD repeat-containing protein 1 (WDR1) regulates the cofilin 1 (CFL1) activity, promotes cytoskeleton remodeling, and thus, facilitates cell migration and invasion. A previous study reported that autoantibodies against CFL1 and ß-actin were useful biomarkers for diagnosing and predicting the prognosis of patients with esophageal carcinoma. Therefore, the present study aimed to evaluate the serum levels of anti-WDR1 antibodies (s-WDR1-Abs) combined with serum levels of anti-CFL1 antibodies (s-CFL1-Abs) in patients with esophageal carcinoma. Serum samples obtained from 192 patients with esophageal carcinoma and other solid cancers. And s-WDR1-Ab and s-CFL1-Ab titers were analyzed using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Compared with those of healthy donors, the s-WDR1-Ab levels were significantly higher in the 192 patients with esophageal, whereas these were not significantly higher in the samples from patients with gastric, colorectal, lung, or breast cancer. In 91 patients treated with surgery, sex, tumor depth, lymph node metastasis, stage and C-reactive protein levels were significantly associated with overall survival, as determined using the log-rank test, whereas the squamous cell carcinoma antigen, p53 antibody and s-WDR1-Ab levels tended to be associated with a worse prognosis. Although no significant difference was observed in the survival between the positive and negative groups of s-WDR1-Abs or s-CFL1-Abs alone in the Kaplan-Meier test, the patients in the s-WDR1-Ab-positive and s-CFL1-Ab-negative groups exhibited a significantly poorer prognosis in the overall survival analysis. On the whole, the present study demonstrates that the combination of positive anti-WDR1 antibodies with negative anti-CFL1 antibodies in serum may be a poor prognostic factor for patients with esophageal carcinoma.

Is High Score of Preoperative Lactate Dehydrogenase to Albumin Ratio Predicting Poor Survivals in Esophageal Carcinoma Patients?

PURPOSE: The lactate dehydrogenase-to-albumin ratio (LAR) has been reported as a potential prognostic biomarker in various cancers; however, only a few pieces of information have been reported on esophageal cancer. Therefore, this study aimed to evaluate the prognostic significance of preoperative LAR in patients with esophageal cancer. METHODS: This study included 236 patients (193 men and 43 women; mean age of 66 years [range, 41-83 years]) with esophageal cancer who underwent curative surgery between September 2008 and March 2020. A total of 107 patients underwent upfront surgery, and 129 patients received neoadjuvant treatment. Patients were assigned into two groups, high and low LAR, based on preoperative LAR using a cutoff value of 6.2. The clinicopathological and prognostic significance of preoperative LAR was evaluated in univariate and multivariate analyses. RESULTS: Patients with deep tumors and neoadjuvant treatment were significantly associated with high LAR (p <0.05). The high LAR group showed a significantly poorer prognosis than the low LAR group (p <0.01). The multivariate analysis for the overall survival showed that deep tumors, lymph node metastasis, and high LAR were independent poor prognostic factors (p <0.05). CONCLUSION: High LAR was a useful poor prognostic biomarker in patients with esophageal cancer.

Comparison between a new assay system, Elecsys® Anti-p53, and conventional MESACUP™ for the detection of serum anti-p53 antibodies: A multi-institutional study.

The sensitivity and specificity of a new automated electrochemiluminescence immunoassay system, Elecsys® Anti-p53 (Elecsys), were compared with that of the conventional serum anti-p53 antibody (s-p53-Ab) enzyme-linked immunosorbent assay kit [MESACUP anti-p53 test (MESACUP)]. Elecsys and MESACUP were used to analyze the levels of s-p53-Abs in patients with esophageal, colorectal and breast cancer. A total of 532 controls and 288, 235 and 329 patients with esophageal, colorectal and breast cancer, respectively, were enrolled. Additionally, the sera of patients with benign diseases of the esophagus, colorectal system and breast, patients with autoimmune diseases and healthy volunteers were analyzed as controls. Sensitivity and specificity were compared between the two assay systems. Positive agreement rates were 58.7% in all samples, 71.2% in esophageal samples, 73.6% in colorectal samples and 35.1% in breast samples. Negative agreement rates for the different cancer types were ≥97.1% and the overall agreement rates were ≥92.3%. When the specificities of the two assays were aligned for all samples, Elecsys demonstrated higher sensitivities for all types of analyzed cancer together, as well as for esophageal, colorectal and breast cancer, respectively. Although positive concordance between the two assay systems was low in terms of specificity, Elecsys had a higher sensitivity than the MESACUP.

Low anti-CFL1 antibody with high anti-ACTB antibody is a poor prognostic factor in esophageal squamous cell carcinoma.

BACKGROUND: Cofilin (CFL1, actin-binding protein) and ß-actin (ACTB) are key molecules in the polymerization and depolymerization of actin microfilaments. The levels of these antibodies were analyzed, and the clinicopathological significance in patients with esophageal carcinoma were evaluated. METHODS: The levels of anti-CFL1 and anti-ACTB antibodies were analyzed in serum samples of patients with esophageal carcinoma and of healthy donors. Eighty-seven cases underwent radical surgery and the clinicopathological characteristics and prognosis was examined. RESULTS: Serum anti-CFL1 antibody (s-CFL1-Ab) levels and anti-ACTB antibody (s-ACTB-Ab) levels were significantly higher in patients with esophageal carcinoma than in healthy donors. Following the receiver operating characteristic curve analysis between healthy donors and esophageal carcinoma, the sensitivity and specificity for serum anti-CFL1 antibody (s-CFL1-Ab) were 53.3% and 68.8%. The sensitivity and specificity for serum anti-ACTB antibody (s-ACTB-Ab) were 54.9% and 67.7%, respectively. Univariate and multivariate analysis showed that s-CFL1-Ab and s-ACTB-Ab levels were not associated with sex, age, tumor depth, lymph node metastasis, or anti-p53-antibody levels. s-ACTB-Ab levels but not s-CFL1-Ab levels significantly correlated with squamous cell carcinoma antigen. Neither s-CFL1-Ab nor s-ACTB-Ab levels alone were obviously related to overall survival. However, patients with low s-CFL1-Ab levels and high s-ACTB-Ab levels exhibited significantly more unfavorable prognoses than those with high s-CFL1-Ab and low s-ACTB-Ab levels. CONCLUSIONS: Serum levels of anti-CFL1 and anti-ACTB antibodies were significantly higher in patients with esophageal carcinoma than in healthy donors. A combination of low anti-CFL1 and high anti-ACTB antibodies is a poor prognostic factor in esophageal carcinoma.

Prognostic significance of preoperative low serum creatine kinase levels in gastric cancer.

PURPOSE: We evaluated the clinicopathological and prognostic significance of preoperative serum creatine kinase (CK) levels in gastric cancer. PATIENTS AND METHODS: The subjects of this retrospective study were 942 patients who underwent surgery without preoperative chemotherapy for gastric cancer (643 men and 299 women), excluding Stage IV gastric cancer, between January, 2001 and December, 2020. We set the cutoff values for CK according to gender, as 64 U/L for men and 57 U/L for women, and evaluated the clinicopathological, prognostic, and gender significance of low CK levels by multivariate analysis. RESULTS: Tumor depth was significantly associated with low serum CK levels (p < 0.001). The low CK group showed significantly worse overall survival than the high CK group (p = 0.01). The prognostic impact of low CK levels was evident only in men (p = 0.009). In women, low CK levels were not an independent risk factor for poor prognosis (p = 0.33). These prognostic impacts of low CK levels on overall survival and recurrence-free survival were similar. CONCLUSION: Low preoperative CK levels in men with gastric cancer were predictive of poor survival. These prognostic impacts of low CK levels were not evident in women.

Serum WT1-271 IgM antibody as a novel diagnostic marker for Gastric Cancer.

The Wilms tumor 1 gene, WT1, is overexpressed in various types of cancer, including gastric cancer. The product of WT1 is highly immunogenic and is a promising target molecule for cancer immunotherapy. The current study aimed to examine the production of WT1-specific IgG and IgM autoantibodies to identify biomarkers of diagnostic value in patients with gastric cancer. IgG antibodies that bind to WT1-derived peptides were obtained, the serum levels of which correlate with those of IgG antibodies against the WT1 protein in patients with intestinal malignancies. The serum levels of IgG and IgM antibodies against the WT1-271 peptide (271-288 amino acids) were examined in 39 healthy individuals and 97 patients with gastric cancer. The positivity cutoff value was determined according to the receiver operating characteristic curve. The association between WT1-271 IgM and the clinicopathological factors and prognosis of patients was additionally analyzed. The results revealed that serum WT1-271 IgM antibody levels in patients with gastric cancer were significantly higher than those in healthy individuals. The sensitivity and specificity of this antibody for gastric cancer were 67.0 and 71.8%, respectively; this sensitivity was improved when compared with conventional tumor markers (P<0.001). There was no statistical difference in WT1-271 IgG antibody levels between patients with gastric cancer and healthy individuals. Serum WT1-271 IgM antibody levels were not significantly associated with clinicopathological factors but were associated with unfavorable prognosis. Serum WT1-271 IgM antibody levels could serve as a diagnostic biomarker in patients with gastric cancer.

Presence of serum RalA and serum p53 autoantibodies in 1833 patients with various types of cancers.

BACKGROUND: RalA is a member of the Ras superfamily of small GTPases. The Anti-RalA autoantibodies (s-RalA-Abs) act as tumor markers in various types of cancer and are negatively associated with the p53 autoantibodies (s-p53-Abs). This study aimed to evaluate the relationship between s-RalA-Abs and s-p53-Abs in various types of cancer. METHODS: A total of 1833 cancer patients (esophageal cancer, 172; hepatocellular carcinoma, 91; lung cancer, 269; gastric cancer, 317; colon cancer, 262; breast cancer, 364; and prostate cancer, 358) and 73 healthy subjects were enrolled in the study. The levels of s-RalA-Abs and s-p53-Abs were analyzed using enzyme-linked immunosorbent assay, and the positivity rates and relations between the two autoantibodies were evaluated. The cutoff values for s-RalA abs and s-p53 abs were set as mean + 2 standard deviation and the values higher than the cutoff values were defined as positive. RESULTS: The titers in all cancer types were significantly higher than those in the controls (P < 0.01). The positivity rates for s-RalA-Abs ranged between 11.7 and 21.5%, and those for s-p53-Abs ranged between 12 and 28.5%. A combined assay of the two antibodies revealed positivity rates of 20.9 and 44.2%. In Stage 0/I/II tumors, the positivity rates of the combination of the two antibodies ranged between 21.5 and 42.3%. The two autoantibodies were complementary to each other in the prostate and breast cancers, but independent in other carcinomas. CONCLUSION: The combined use of s-RalA-Abs and s-p53-Abs tended to increase the positivity rate in all cancers, including Stage 0/I/II cancers.

Preoperative Low Serum Calcium Levels Predict Poor Prognosis for Patients with Esophageal Cancer.

PURPOSE: Hypercalcemia has been reported as a poor prognostic factor in malignant tumors. However, no report has shown the clinical impact of serum calcium levels on patients with esophageal cancer. We evaluated the prognostic impact of preoperative serum calcium levels on patients with esophageal cancer. METHODS: We evaluated 240 patients (197 men, 43 women; mean age, 66 years; age range, 34-85 years) with esophageal cancer who underwent radical surgery between September 2008 and December 2017. After assigning the patients to two groups (high calcium group, 8.8 mg/dL or more and low calcium group, 8.7 mg/dL or less), we compared the groups' overall survival and the clinicopathological features. The clinicopathological and prognostic significance of preoperative serum calcium levels were evaluated in a univariate and multivariate analysis. RESULTS: The patients with deep tumors showed low serum calcium levels significantly more frequently (P <0.05). The low calcium group showed a significantly worse prognosis than the high calcium group (P <0.05). However, low serum calcium level was not an independent poor prognostic factor. CONCLUSIONS: Preoperative low serum calcium levels were associated with advanced tumors. Low serum calcium might be associated with esophageal cancer progression.

Preoperative low serum creatine kinase is associated with poor overall survival in the male patients with esophageal squamous cell carcinoma.

BACKGROUND: Serum creatine kinase level has been reported to be a prognostic indicator in breast or lung cancers but no reports have been in esophageal cancer. We analyzed the prognostic significance of preoperative serum creatine kinase level in patients with esophageal carcinoma. METHODS: We evaluated the preoperative serum creatine kinase levels of 148 patients (118 male and 30 female) with esophageal squamous cell carcinoma. According to their median serum creatine kinase levels, we divided the patients into high and low serum creatine kinase groups. Univariate and multivariate analyses were used to evaluate the impact of serum creatine kinase level on the prognosis of the patients. RESULTS: The tumor depth (P < 0.01) and stage (P < 0.01) were significantly associated with serum creatine kinase levels. The prognosis was worse in the low serum creatine kinase group than in the high serum creatine kinase group (P = 0.02). In the subgroup analysis, although no survival difference was observed in the female patients between the groups (P = 0.171), the survival of low serum creatine kinase group was significantly worse than that of high creatine kinase group in the male patients (P = 0.001). Cox proportional hazard regression analysis revealed that nodal status (P = 0.019) and serum creatine kinase level (P = 0.047) were independent risk factors associated with overall survival in the male patients. CONCLUSIONS: Preoperative low serum creatine kinase level was useful in predicting overall survival in the male patients with esophageal squamous cell carcinoma.

Identification of serum anti-striatin 4 antibodies as a common marker for esophageal cancer and other solid cancers.

Solid cancers have a poor prognosis, and their morbidity and mortality after surgery is high. Even after radical surgery for esophageal cancer, there have been cases of early postoperative death. The present study therefore aimed to explore new tumor markers that can predict the early postoperative prognosis. To identify antibody markers, serological antigens were identified using recombinant cDNA expression cloning (SEREX). The results identified striatin 4 (STRN4) as the antigen recognized by serum IgG antibodies in patients with esophageal cancer. After performing an amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), it was revealed that when compared with healthy donors, serum anti-STRN4 antibody (STRN4-Ab) levels were significantly higher not only in patients with esophageal cancer but also to lesser extent, in those with gastric cancer, colorectal cancer, lung cancer and breast cancer. Compared with STRN4-Ab-negative patients with esophageal cancer, STRN4-Ab-positive patients had a poorer postoperative prognosis at early stages, suggesting that STRN4-Abs may be useful for predicting poor early-stage prognoses of patients with esophageal cancer. The positive diagnosis rates of esophageal cancer using the STRN4-Ab marker and conventional markers, including squamous cell carcinoma antigen and p53 antibody alone, were 26.4, 35.2 and 19.1% respectively; a result that increased up to 59.1% by combining all three markers. Serum STRN4-Ab may serve as a novel marker of esophageal cancer.

Association of Serum Anti-PCSK9 Antibody Levels with Favorable Postoperative Prognosis in Esophageal Cancer.

BACKGROUND: Esophageal cancer often appears as postoperative metastasis or recurrence after radical surgery. Although we had previously reported that serum programmed cell death ligand 1 (PD-L1) level correlated with the prognosis of esophageal cancer, further novel biomarkers are required for more precise prediction of the prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with the cholesterol metabolism. But there was no report of relationship between serum PCSK9 antibody and cancer. Therefore, we investigated whether anti-PCSK9 antibodies could be a novel biomarker for solid cancer. METHODS: Serum levels of anti-PCSK9 antibodies and antigens in patients with solid cancer were analyzed using amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The reactivity of serum antibodies against recombinant PCSK9 protein was investigated by Western blotting, and the expression of PCSK9 antigens in esophageal cancer tissues was examined by immunohistochemical staining. RESULTS: AlphaLISA showed that serum anti-PCSK9 antibody (s-PCSK9-Ab) levels were significantly higher in patients with esophageal cancer, gastric cancer, colorectal cancer, lung cancer, and breast cancer than in healthy donors, and patients with esophageal cancer had the highest levels. The presence of serum antibody in patients was confirmed by Western blotting. There was no apparent correlation between s-PCSK9-Ab and PCSK9 antigen levels. Immunohistochemical staining demonstrated the expression of PCSK9 antigen in both the cytoplasm and nuclear compartments of esophageal squamous cell carcinoma tissue but not in normal tissue. Compared with patients with low s-PCSK9-Ab levels, those with high s-PCSK9-Ab levels had a favorable postoperative prognosis after radical surgery for esophageal cancer. In the multivariate analysis, tumor depth and s-PCSK9-Ab level were identified as independent prognostic factors. In the univariate analysis of clinicopathological features, high PCSK9 antibody levels were not associated with sex, age, location, tumor depth, lymph node status, squamous cell carcinoma antigen, or p53-Ab, whereas they correlated significantly with PD-L1 levels, which were associated with unfavorable prognosis. Correlation between s-PCSK9-Ab and PD-L1 levels was also confirmed in the logistic regression analysis; therefore, low s-PCSK9-Ab levels could discriminate another poor prognosis group other than high-PD-L1 group. CONCLUSIONS: Patients with solid cancer had higher s-PCSK9-Ab levels than healthy donors. High s-PCSK9-Ab levels indicated better prognosis for overall survival after surgery in patients with esophageal cancer.

Prevalence of serum galectin-1 autoantibodies in seven types of cancer: A potential biomarker.

Although serum galectin-1 antibodies (s-GAL-1-Abs) have been evaluated in a small number of patients with cancer, a large series of patients with different cancer types have not been reported. The current study evaluated 1,833 patients with esophageal cancer (n=172), gastric cancer (n=317), colorectal cancer (n=262), hepatocellular carcinoma (n=91), prostate cancer (n=358), breast cancer (n=364), lung cancer (n=269) and 72 healthy individuals. s-GAL-1-Abs levels were analyzed using an originally developed ELISA system. A cut-off optical density value was determined as the mean (0.053) + 3 standard deviations (0.105) of sera from healthy controls. The results revealed that the positive rate of s-GAL-1-Abs in patients with hepatocellular carcinoma (16.7%) and lung cancer (13.8%) were significantly higher compared with the other groups: Esophageal cancer (11.6%), colorectal cancer (11.5%), prostate cancer (7.3%), gastric cancer (6.9%), breast cancer (6.9%) and healthy controls (4.2%). Although the positive rates of s-GAL-1-Abs in different cancer types were relatively low, s-GAL-1-Abs may be useful for patients with hepatocellular carcinoma and lung cancer.

[Intracorporeal Anastomosis in Laparoscopic Colectomy with Blood Flow Confirmation by Fluorescence Angiography].

We verified the significance of intestinal blood flow evaluation by indocyanine green(ICG)fluorescence during intracorporeal anastomosis in laparoscopic colectomy which was performed from July 2019 to December 2019 in our institute. For 11 cases of intracorporeal anastomosis, we examined the patient background, surgical results such as operation time and blood loss, evaluation of intraoperative ICG blood flow, and perioperative complications. In all cases, after the mesentery treatment in the abdominal cavity and before the intestinal incision, the blood flow of the planned anastomosis site was evaluated by ICG fluorescence observation. No cases were required to be changed the anastomosis site. The average operation time was 240 minutes and the average blood loss was 10 mL. There were no perioperative complications such as anastomotic leakage, stenosis, bleeding, nor wound infection. It was suggested that the intraoperative evaluation of ICG blood flow during intracorporeal anastomosis in laparoscopic colectomy may contribute to the suppression of complications such as anastomotic leakage.

[A Study of Laparoscopic Stoma Creation for Patients with Colorectal Cancer].

There are few reports on laparoscopic stoma creation; we report here our experience with laparoscopic stoma creation. PATIENTS AND METHODS: Seven patients who underwent laparoscopic stoma creation between April 2019 and December 2019 were studied and their clinical outcome was evaluated retrospectively. Operation approach: We performed a colostomy in the transverse colon. At first, we insert a 12 mm first port into the site of stoma marking. And more, we insert three 5 mm ports on the opposite side of the first port. We remove the adhesions of the intestinal tract and create a colostomy. RESULT: We changed open method 2 cases out of 7 cases due to extensive adhesion. In laparoscopically, we had an operation time of 97 (42-130) minutes and a blood loss of 5(2-40) mL. We had no postoperative complications or stoma problems. CONCLUSION: Laparoscopic stoma creation was useful due to few postoperative complications and can be rapidly transferred to chemotherapy.

Prognostic impact of CEA/CA19-9 at the time of recurrence in patients with gastric cancer.

PURPOSE: We evaluated the clinical impact of the carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) values at the time of recurrence in gastric cancer patients. METHODS: Among 790 patients with R0 resected gastric cancer without neoadjuvant therapy between 2004 and 2017, 89 recurrence cases were retrospectively evaluated. The clinical impact of CEA and CA19-9 values on recurrence sites and post-recurrent prognosis were evaluated using univariate and multivariate analyses. RESULTS: The positive rates of CEA and CA19-9 at recurrence were significantly higher than the preoperative positive rates (CEA, 56% vs 24%; CA19-9, 37% vs 15%). Although CA19-9-positive patients at recurrence exhibited a poor survival, the difference was not significant. The positive rates of CEA at liver or lymph node recurrence were significantly higher than the preoperative positive rates. The positive rate of CA19-9 at peritoneal recurrence was significantly higher than the preoperative positive rate. CA19-9-positive patients at recurrence exhibited worse prognosis than CA19-9-negative patients, although the difference was not significant. At lymph node recurrence, CA19-9-positive patients exhibited a significantly worse survival than CA19-9-negative patients. CONCLUSION: In recurrent gastric cancer, the positive status of CA19-9 at recurrence might have a negative prognostic impact after recurrence; particularly, in patients with lymph node recurrence.

New Assay System Elecsys Anti-p53 to Detect Serum Anti-p53 Antibodies in Esophageal Cancer Patients and Colorectal Cancer Patients: Multi-institutional Study.

BACKGROUND: Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). METHODS: Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. RESULTS: Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 µg/mL (range < 0.02-29.2 µg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 µg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer. CONCLUSIONS: The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates.

Possible predictive significance of serum RalA autoantibodies on relapse-free survival in patients with colorectal cancer.

RalA protein, a member of the Ras superfamily of small GTPases, is a tumor antigen that induces serum RalA antibodies (s-RalA-Abs). The present study explored the clinicopathological and prognostic significance of s-RalA-Abs in patients with colorectal cancer. Serum samples were obtained from 314 patients with colorectal cancer at stage 0/I (n=71), stage II (n=86), stage III (n=78), stage IV (n=64) and recurrence (n=15). Samples were analyzed for the presence of s-RalA-Abs using ELISA. The cutoff optical density value was fixed at 0.324 (mean of heathy controls + 3 standard deviations). The overall positive rate for serum anti-RalA antibodies was 14%. The presence of s-RalA-Abs was not significantly associated with clinicopathological characteristic factors. Additionally, the s-RalA-Abs(+) group demonstrated significantly poor relapse-free survival rates. The s-RalA-Abs (+)/carcinoembryonic antigen (CEA)(+) group exhibited the worst prognosis and s-RalA-Abs(+)/CEA(+) was an independent risk factor for poor relapse-free survival. Although the positive rate was not high, s-RalA-Abs may be a useful predictor of poor relapse-free survival in patients with colorectal cancer.

Usefulness of serum miR-1246/miR-106b ratio in patients with esophageal squamous cell carcinoma.

The function of microRNAs (miRs) is associated with the development and progression of various malignancies, with miRs presenting stably in the serum. The current study assessed the role of miR-1246 and miR-106b in the serum of patients with esophageal squamous cell carcinoma (ESCC). A comprehensive microarray analysis of miR expression was performed using the serum of patients with ESCC, which were subsequently validated via reverse transcription-quantitative PCR. A total of 55 test samples were obtained from Chiba University and 101 validation samples were gained from Chiba Cancer Center. The results revealed that miR-1246 expression significantly increased and miR-106b expression significantly decreased in each cohort. Receiver operating characteristic analysis revealed that the area under the curve (AUC) value of miR-1246 was 0.816 (sensitivity, 72.7%; specificity, 69.2%) and 0.779 (sensitivity, 71.3%; specificity, 70.6%) for the test and validation cohorts, respectively. The AUC of miR-106b was 0.716 (sensitivity, 65.5%; specificity, 61.6%) and 0.815 (sensitivity, 74.3%; specificity, 73.5%), respectively. In addition, the AUC of the miR-1246/miR-106b ratio was 0.901 (sensitivity, 80.0%; specificity, 80.0%) and 0.903 (sensitivity, 82.1%; specificity, 82.3%), respectively, which indicated a higher diagnostic ability compared with that of miR-1246 or miR-106b alone. The high miR-1246/miR-106b ratio group was associated with clinicopathological factors such as depth of invasion, progression, lymph node metastasis, and poor prognosis. Therefore, effective biomarkers may be generated by combining individual miRs obtained by comprehensive analysis of ESCC patient sera.

Inducing multiple antibodies to treat squamous cell esophageal carcinoma.

BACKGROUND: The positive response and the clinical usefulness of 14 serum antibodies in patients with esophageal squamous cell carcinoma (ESCC) were examined in this study. The Cancer Genome Atlas (TCGA) was used to investigate the frequency of gene expressions, mutations, and amplification of these 14 antigens and also the possible effects of antibody induction. METHODS: Blood serum derived from 85 patients with ESCC was collected and analyzed for the 14 antibodies using ELISA. The prognosis between positive and negative antibodies were then compared. The antibody panel included LGALS1, HCA25a, HCC-22-5, and HSP70. RESULTS: Patient serum was positive for all antibodies, except VEGF, with the positive rates ranging from 1.18 to 10.59%. Positive rates for LGALS1, HCA25a, HCC-22-5, and HSP70 were > 10%. TCGA data revealed that all antigen-related genes had little or no mutation or amplification, and hence an increase in gene expression affected antibody induction. The positive results from the panel accounted for the positive rate comparable to the combination of CEA and SCC. No significant association was observed between the presence of antibodies and disease prognosis. CONCLUSIONS: The detection rates of LGALS1, HCA25a, HCC-22-5, and HSP70 were 10% higher in patients with ESCC. Gene overexpression may be involved in such antibody production. These four antibodies were applied as a panel in comparison with conventional tumor markers. Moreover, it was confirmed that the combination of this panel and the conventional tumor markers significantly improved the positive rate.