Co-expression of CMTM6 and PD-L1: a novel prognostic indicator of gastric cancer

2020 ◽  
Author(s):  
Chao Zhang ◽  
Wen An ◽  
Yuen Tan ◽  
Huimian Xu

Abstract Background CKLF Like MARVEL Transmembrane Domain Containing 6 (CMTM6) is involved in the epigenetic regulation of genes and tumorigenesis. Programmed cell death ligand 1 (PD-L1) is closely related to the prognosis of some human cancers. CMTM6 is a key regulator of PD-L1 in many cancers. The purpose of this study was to investigate the expressions of these proteins in gastric cancer and the correlations with clinicopathological features and survival. Methods The expression levels of CMTM6 and PD-L1 were examined in 185 gastric cancer specimens by immunohistochemistry. Chi-square test was used to analyze the relationship between CMTM6 and PD-L1 expressions and clinicopathological characteristics. Kaplan-Meier method and log-rank test were used to analyze the survival data of patients.Results The positive expression rates of CMTM6 and PD-L1 were 78.38% (145/185) and 75.68% (140/185), respectively. High expression of CMTM6 and PD-L1 was correlated with Borrmann type ( P < 0.001), N stage ( P = 0.002), peritoneal metastasis ( P = 0.007) and TNM stage ( P = 0.038). The expression of CMTM6 and PD-L1 in gastric cancer tissues was positively correlated (Pearson's coefficient test, r = 0.260; P < 0.001). High expression of CMTM6 was correlated with poor prognosis (HR = 1.668; 95% CI = 1.032–2.695; P = 0.037). High expression of both CMTM6 and PD-L1 could be used as an independent factor for overall survival (HR = 1.554; 95% CI = 1.011–2.389; P = 0.044). Conclusions The combined detection of CMTM6 and PD-L1 may be used as an indicator for judging the prognosis of gastric cancer.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Zhang ◽  
Shutao Zhao ◽  
Xudong Wang

Abstract Background CKLF Like MARVEL Transmembrane Domain Containing 6 (CMTM6) is involved in the epigenetic regulation of genes and tumorigenesis. Programmed cell death ligand 1 (PD-L1) is closely related to the prognosis of some human cancers. CMTM6 is a key regulator of PD-L1 in many cancers. The purpose of this study was to investigate the expressions of these proteins in gastric cancer and the correlations with clinicopathological features and survival. Methods The expression levels of CMTM6 and PD-L1 were examined in 185 gastric cancer specimens using immunohistochemistry, quantitative real-time PCR and Western blot. Immunofluorescence was used to examine the localizations of CMTM6 and PD-L1. Chi-square test was used to analyze the relationship between CMTM6 and PD-L1 expressions and clinicopathological characteristics. Kaplan–Meier method and log-rank test were used to analyze the survival data of patients. Results The positive expression rates of CMTM6 and PD-L1 in gastric cancers were 78.38% (145/185) and 75.68% (140/185), respectively. CMTM6 and PD-L1 were both mainly expressed in the cell membrane and nucleus of gastric cancer tumor cells. High expression of CMTM6 and PD-L1 was correlated with Borrmann type (P < 0.001), N stage (P = 0.002), peritoneal metastasis (P = 0.007) and TNM stage (P = 0.038). CMTM6 and PD-L1 expression in gastric cancer tissues showed a positive correlation (Pearson’s coefficient test, r = 0.260; P < 0.001). CMTM6 may positively regulate PD-L1 expression. High expression of CMTM6 was correlated with poor prognosis of gastric cancer patients (HR = 1.668; 95% CI = 1.032–2.695; P = 0.037). High expression of both CMTM6 and PD-L1 may be an independent factor for overall survival (HR = 1.554; 95% CI = 1.011–2.389; P = 0.044). Conclusion The combined detection of CMTM6 and PD-L1 may be used as an indicator for judging the prognosis of gastric cancer patients.


Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Margherita Ratti ◽  
Nicola Valeri ◽  
Jens Claus Hahne ◽  
Andrea Lampis ◽  
Michele Ghidini ◽  
...  

e15566 Background: Identification of prognostic biomarkers for gastric cancer (GC) patient selection is compelling to improve survival outcomes. Microsatellite instability (MSI) is related with a positive prognostic effect in GC, whereas perioperative chemotherapy resulted detrimental in this subgroup. In metastatic GC, immunotherapy with anti-PD1/PD-L1 drugs has shown promising results. Nevertheless, in early stages, data on the relation between MSI, clinic-pathological features, PD-L1 expression and overall survival (OS) remains sparse, especially in Western population. In our study, the prognostic role of MSI, clinic-pathological features and PD-L1 expression in a cohort of Italian GC patients was examined. Methods: CP data of 148 consecutive stage I-III GC pts resected in Cremona Institute between 2010 and 2014 (mostly chemo and/or radio-naive) were collected. MSI analysis was performed on tissue samples for all cases by polymerase chain reaction. PDL-1 expression, evaluated by immunohistochemistry, was assessed in MSI group. Differences between subgroups were evaluated with Chi-square test; Kaplan-Meier method and Long Rank test were used to calculate OS. Results: Female sex (p=0.012), earlier TNM stages (p=0.011) and limited nodal involvement (p=0.29) significantly correlated with MSI status. MSI is significantly associated with better prognosis, exhibiting an advantage of 28.6 months in OS compared with microsatellite stable subgroup (p<0.001). Most MSI patients expressed PD-L1. MSI patients without PD-L1 expression showed higher percentage of clinical features correlated with better prognosis compared with PD-L1 expressing MSI patients and MSS subgroup. Conclusions: MSI is an independent prognostic biomarker in GC and identifies a subset of patients with better OS and specific clinic-pathological features, including high percentage of PD-L1 expression. MSI could represent a promising biomarker to select patients for chemotherapy versus immunotherapy in non-metastatic disease.


2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  

Abstract Background: Previous studies have demonstrated that microRNAs (miRNAs) played a crucial role in various diseases, including cancers. The aim of the study was to evaluate the clinical significance of miR-124 in patients with cholangiocarcinoma (CCA).Methods: The expression pattern of miR-124 was detected in CCA tissues using quantitative reserve transcription polymerase chain reaction (qRT-PCR). The correlation of miR-124 expression with clinicopathological features and overall survival of patients were explored using chi-square test, Kaplan-Meier methods and Cox regression analyses.Results: The miR-124 expression level was strong down-regulated in CCA tissues compared with normal para-cancerous tissues (P<0.001). Moreover, aberrant miR-124 expression was significantly associated with differentiation (P=0.045) and lymph node metastasis (P=0.040). In addition, Kaplan-Meier method and log-rank test revealed that patients with low miR-124 expression has a poorer overall survival compared with those with high miR-124 expression (P=0.002). Furthermore, multivariate analysis confirmed that miR-124 expression (P=0.006; HR=2.006; 95%CI: 1.224-3.289) was an independent prognostic indicator in CCA.Conclusions: Collectively, our results defined miR-124 expression plays important roles in CCA patients. MiR-124 expression might used as a valuable prognostic biomarker for patients with CCA.


2021 ◽  
Author(s):  
Huining Fan ◽  
Xiang-Yun Zhao ◽  
Rui Liang ◽  
Xiao-Yu Chen ◽  
Jing Zhang ◽  
...  

Abstract Background: CircRNAs are a new subset of noncoding RNAs formed by covalent closed loops and play crucial roles in the regulation of cancer gene expression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain indistinct. This study aimed to explore the role and mechanism of hsa_circ_0006421 (circPTK2) in GC.Methods: The differential expression of circRNAs between GC tissues and adjacent normal tissues were identified by a circRNA expression profiling. Associations of circPTK2 or miR-134-5p expression with clinicopathological characteristics and prognosis of GC patients were analyzed by chi-square of Fisher’s exact tests and Kaplan-Meier analysis. CCK8, colony formation, EdU assays and animal models were performed to assess the effects of circPTK2 on proliferation and invasion of GC cells. CircPTK2-specific probes were used to purify the RNA pulled down from the circPTK2, and enrichment of circPTK2 and miR-134-5p was detected by qRT-PCR. The effects of circPTK2 on miR-134-5p expression and CELF2/PTEN signaling were examined by qRT-PCR and Western blotting analysis. Results: Low expression of circPTK2 and high expression of miR-134-5p were related to the poor survival, and high expression of miR-134-5p was related to the tumor recurrence in GC patients. Overexpressing circPTK2 suppressed the proliferation, colony formation, DNA synthesis and cell invasion as well as xenograft tumor growth and lung metastasis in vitro and in vivo, whereas silencing circPTK2 had the opposite effects. Moreover, circPTK2 was negatively correlated and co-localized with miR-134-5p in the cytoplasm of GC tissue cells. circPTK2 bound to and sponged miR-134-5p in GC cells, and miR-134-5p facilitated cell growth and invasion but attenuated circPTK2 induced tumor suppressive effects and CELF2/PTEN signaling activation in GC cells. Conclusions: circPTK2 functions as a tumor suppressor in GC by sponging miR-134-5p and activating the CELF2/PTEN axis.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4544-4544
Author(s):  
A. Tsuburaya ◽  
H. Narahara ◽  
H. Imamura ◽  
K. Hatake ◽  
H. Imamoto ◽  
...  

4544 Background: IRI-S had longer in median survival time (MST) than S-1 alone, and was well tolerated in previously untreated AGC, but not statistically significant. Considering 68 patients (pts) were censored, further follow-up was needed to confirm the OS with more precision (Imamura et al. ASCO-GI 2008). We now present updated results of OS and exploratory analysis with the prolonged 2.5 year follow-up data. Methods: Treatments Arm A (oral S-1 80 mg/m2/day from Day 1 to 28, q6w), or Arm B (IRI-S; oral S-1 80 mg/m2/day from Day 1 to 21 and intravenous irinotecan 80 mg/m2 on Days 1 and 15, q5w) were continued until disease progression or unacceptable toxicities were observed. The primary endpoint was to compare OS between groups. This updated result was regarded as exploratory position. Results: Although the MST of Arm A was 319 days (95%Cl: 286–395) and of Arm B was 389 days (95%Cl: 324–459), Arm B didn’t show statistically significant superiority to Arm A (log-rank test p=0.54; hazard ratio (HR) =0.93). The 1-year survival was 45.0% in Arm A and 52.0% in Arm B, and the 2-year survival was 22.5% and 18.0%, respectively. Response rate was significantly different (Arm A/B, 26.9%/41.5%; chi-square test p=0.04) in 187 patient evaluated by RECIST criteria. Time to treatment failure was also favored in Arm B (median=138 days) compared to Arm A (111 days; log-rank test p=0.16; HR=0.85). In subset analyses, two groups showed possibility of clinical benefit in Arm B. The HR of diffuse type group was 0.71 (95%Cl: 0.52–0.96), and of PS1, 2 group was 0.63 (95%Cl: 0.42–0.95). As post protocol treatment, 45.6% of Arm A patients received an irinotecan-based regimen, and the MST of them was 496 days (95%Cl: 395–573). Conclusions: IRI-S did not show statistically significant superiority to S-1 alone in OS with this follow-up data. Post protocol treatment, effective treatment after S-1 failure might have affected survival. According to exploratory analyses, IRI-S may have clinical benefit in early-term of treatment, group of the diffuse type and that of PS1, 2. We need more considering predictive factors, because the gastric cancer is heterogeneous adenocarcinoma. [Table: see text]


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi48-vi48
Author(s):  
Yusef Syed ◽  
Manali Rupji ◽  
Jeffrey Switchenko ◽  
Bree Eaton ◽  
Jeffrey Olson ◽  
...  

Abstract BACKGROUND WHO grade II (atypical) meningiomas are treated with surgical resection, often followed by adjuvant fractionated radiation therapy (FRT). The increased availability of frameless stereotactic radiosurgery (SRS) presents an opportunity to offer patients a high biological effective dose over fewer fractions. Here we study the patterns of care and outcomes of these two forms of adjuvant RT. METHODS Patients with atypical meningioma were abstracted from the National Cancer Database (NCDB). Descriptive statistics were reported, and differences between treatment groups were assessed using either a chi-square test or ANOVA. Patients were grouped by treatment type and Kaplan Meier (KM) analysis was performed to compare overall survival (OS) using a log rank test. Univariable (UVA) and multivariable (MVA) cox regression analyses were completed. RESULTS Of 10,015 cases diagnosed from 2004-2016, 7,153 received surgery alone, 2,059 received surgery and adjuvant FRT (S+RT), and 362 received adjuvant SRS (S+SRS). The use of adjuvant RT increased by 71.8% for S+RT and 97.8% for S+SRS. In 2004, 15.1% of 443 registered patients received S+RT and 2.26% received S+SRS, while in 2016 these figures were 26.0% and 4.47%, respectively, for the 1051 registered patients (p&lt; 0.001 and 0.022, respectively). For the 8,636 patients with survival data there was no significant difference in median OS between S+RT and S+SRS (130 months vs. 125 months, log rank p=0.935). On UVA, S+RT conferred better survival compared to surgery alone (HR 0.81 [0.72-0.91], p&lt; 0.001) while S+SRS trended towards better survival (HR 0.82 [0.64-1.06], p=0.124). On MVA, no significant OS benefit was seen with S+RT (HR 0.96 [0.85-1.08], p=0.491) or S+SRS (HR 0.90 [0.69-1.16], p=0.413) versus surgery alone. CONCLUSIONS While the use of adjuvant RT for atypical meningioma has increased substantially since 2004, OS is comparable between FRT and SRS. The data presented here support further prospective investigation of adjuvant SRS.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1046-1046
Author(s):  
Darko Skrobo ◽  
Naomi Walsh ◽  
Jose Berenguer ◽  
Janice Maria Walshe ◽  
Michaela Jane Higgins ◽  
...  

1046 Background: The introduction of anti-H2 targeted therapies has resulted in substantially improved outcomes for patients (pts) with H+MBC, yet despite survival prolongation, most patients so-treated will still ultimately die from MBC. Some patients do however, achieved prolonged remissions. In this report we outline the long-term outcomes of patients with H+MBC who were treated in our institution, with at least five-year follow-up from the diagnosis of MBC. Methods: As part of our larger single-institution “Thousand Patient HER-2 Database”, we conducted a retrospective review of all patients in whom a diagnosis of H+MBC was made prior to December 2015 (range 2000-2015 years). The DR5 category included only those who had never experienced relapse or progression following initial anti-H2 therapy for MBC, and who were alive at 5 years. Patients were designated as (1) DR5, defined as never relapse with an overall survival (OS) > 5 years; (2) nonDR, which included those who had no or shorter remission, but also included nine pts who did achieve a 5 year CR, but who subsequently relapsed. OS was calculated from the date of diagnosis of MBC. The frequency distribution was assessed by Fisher’s Exact Test or Chi-Square Test, as appropriate. OS and PFS were calculated according to Kaplan Meier method, and evaluated by Log-rank test. Univariate and multivariate Cox proportional hazards regression analysis was used to evaluate the effect of clinicopathological features on OS and PFS. Results: A total of 245 patients diagnosed with advanced H+MBC were identified. The median survival was 38 months, (range 0.3 – 248 months). Among these, 85 patients (35%) experienced an OS > 5 years, with 34 designated as DR5. The median OS for DR5 was 117 months, whereas nonDR (n = 211) had median OS of 33 months. The median age was similar between groups (DR5 53 yrs vs nonDR 56 yrs). A higher incidence of visceral disease was present in nonDR compared to DR5 (69% vs 44%). Of all patients diagnosed with de novo H+MBC, 23% achieved DR5. Presence of visceral disease, number of metastases and site of metastases were statistically significant negative predictors of achieving DR5 (P < 0.05). Presence of ER positive disease was not associated with OS. Conclusions: A meaningful subset of patients (14%) with advanced H+MBC achieve prolonged remission beyond five years with H2 targeted therapy. Nearly one quarter of those with de novo H+MBC achieve DR5. As de novo H+MBC now constitutes a higher proportion of all H+MBC than it did in the pre-trastuzumab era, an increasing proportion of H+MBC may now be achieving DR5. Prospective identification of variables to predict DR5 could assist in the stratification of patients for whom additional therapy is needed.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1196-1196
Author(s):  
Valter Gattei ◽  
Paolo Sonego ◽  
Riccardo Bomben ◽  
Michele Dal ◽  
Dania Benedetti ◽  
...  

Abstract Introduction: Although expression of β1 integrins was analyzed in B-cell chronic lymphocytic leukemia (B-CLL), little is known about the clinical behaviour and the phenotyic profile of B-CLLs with different patterns of β1 integrin expression. Methods: Expression of β1 integrins (α1-α6) was investigated by flow cytometry along with other 30 surface molecules (B-cell markers, cell-adhesion-molecules, activation inducers, complement activity regulators) in 155 B-CLLs, 106 characterized for clinical stage (Rai’s stages), 121 for IgVH mutations, 79 for ZAP-70 expression and 109 with survival data. Results: In agreement with previous studies, also in our B-CLL series CD49c, CD49d and, to a lesser extent, CD49e resulted the most expressed β1 integrins, with mean expression values, evaluated as % of positive cells, of 59%, 36% and 26% (range 1-100%), respectively. Since expression of CD49c and CD49d have been recently identified by us as part of the immunophenotypic signatures of B-CLLs with different prognosis (J Cell Physiol204, 113, 2005), the present study was designed to define: 1) the real prognostic impact and the optimal cutoffs for CD49c and CD49d splitting patients into two groups with different survivals; 2) the immunophenotypic and molecular features of B-CLL subsets expressing different levels of CD49c and CD49d. 1) By applying the maximally selected log-rank statistics, we identified cutoff values of 40% and 30% of positive cells for CD49c and CD49d, respectively; therefore, B-CLL cases were divided in CD49chigh or CD49clow and CD49dhigh or CD49dlow if the expression of the molecules was above or below their respective cutoffs. The CD49chigh B-CLL subset (n=78) displayed longer survival as compared to CD49clow cases (n=31; p=2.0x10-2, log-rank test); conversely, CD49dhigh B-CLLs (n=46) had shorter survivals, as compared to the CD49dlow subset (n=62; p=1.2x10-3). 2) Supervised analyses were performed by comparing the expression of a wide panel of surface antigens in CD49chigh vs. CD49clow and CD49dhigh vs. CD49dlow B-CLLs. In addition, B-CLL subgroups, as identified by CD49c and CD49d expression, were compared for IgVH mutations (2% cutoff), ZAP-70 expression (30% cutoff) and Rai’s stages distribution (stages 0-I vs. II-IV). According to these analyses, CD62L, CD22, CD55, CD29, CD11c, CD54 and CD40 were the molecules significantly over-expressed in good prognosis CD49chigh B-CLLs, as compared to CD49clow cases (p&lt;0.05; t-test); consistently, CD49chigh vs. CD49clow B-CLLs had mutated:unmutated (M:UM) ratios of 2.2 vs. 0.6 (p=9.2x10-3; Chi-square Test). Bad prognosis CD49dhigh B-CLLs, as compared to CD49dlow cases, over-expressed CD38, CD29, CD49e, CD79b and displayed a lower expression of CD11c (p&lt;0.05). In the same subsets, M:UM ratios were 0.6 (CD49dhigh) or 3.4 (CD49dlow; p=4.2x10-5; Chi-square Test); finally, the frequency of both ZAP-70+ cases and cases with advanced Rai’s stages (II-IV) was significantly higher (p=5.6x10-4 and 2.9x10-2, respectively) in CD49dhigh B-CLLs. Conclusion: CD49c and CD49d identify B-CLL subsets with peculiar clinico-biological features, allegedly originating from different normal B cell counterparts; under a clinical standpoint, CD49c and CD49d may be employed as additional prognosticators for B-CLLs.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23034-e23034
Author(s):  
Luciana Paola Acosta ◽  
Martin Eduardo Richardet ◽  
Matias Molina ◽  
Eduardo Richardet

e23034 Background: In kidney cancer, some important prognostic factors of survival are known and inflammation plays a key role. It has been proven that cancer progress is not only determined by the characteristics of the tumor but also by the response of the host. It is known that a high RNL has been identified as an independent prognostic factor associated to poor survival in several/different types of cancer, including breast cancer, colon cancer, gastric cancer, mesothelioma and pancreas. The primary aim was to evaluate if RNL can be used as a prognostic indicator of SLP in patients with advanced CCR with 1st line treatment with tirosin-kinasa inhibitors. The secondary aim was to evaluate whether there was a relationship between prognostic factors, smoking habits, BMI, anemia, calcemia, KPS and nephrectomized patients as opposed to those who were not operated with RNL and SLP. Methods: Retrospective and analytical study. The medical histories from patients with metastatic kidney cancer diagnosis were analyzed as well as those who were undergoing treatment with Sunitinib and Pazopanib. The cut value of > ó < 3 was taken as a reference point for RNL. Overall survival analysis will be evaluated through the Kaplan-Meier curve and the meaning will be verified by the log-rank test. The multivariate analysis will be done through the Chi-square test. Results: A total of 65 patients were included in this study. 50 patients (75.38%) received treatment with Sunitinib and 15 patients (24.62%) with Pazopanib. It was observed that RNL < 3 was correlated with a higher SLP 21,6 months vs 8.9 months, p = 0,00002 and it was statistically significant. In subgroup analysis, those patients with normal values of corrected calcium the survival was 20 months vs 12, 2 months (p: 0.01), non-smokers 21 months vs 12 months (p: 0.05), KPS > 1 17,72 months Vs 8,8 months (p: 0.03) and a RNL < 3 showed a higher survival in a statistically significant way. There were no differences in survival when we performed the anemia analysis, BMI, smoking habits and KPS 0 to 1. Conclusions: We can conclude that those patients with RNL < 3 and who had already undergone treatment with ITK revealed a better SLP in a statistically significant way.


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