Clinicopathologic features and prognostic value of DNA mismatch protein expression patterns in stage Ⅱ/Ⅲ colorectal cancer.

Author(s):  
An Shang ◽  
Zeyun Zhao ◽  
Zhaoyong Wang ◽  
Donglin Li ◽  
Yu Guo ◽  
...  

Abstract Background MSI CRCs were associated with better prognosis and limited predictive value for adjuvant chemotherapy. However, whether the same is true in Northeastern China is still unclear. The aim of the present study was to evaluate the association of clinicopathologic features and MMR/MSI status determined with immunohistochemistry analysis in Northeast China patients with stage Ⅱ/Ⅲ CRCs. Particularly, we sought to detect the relationship between MMR/MSI status and efficacy of oxaliplatin and fluoropyrimidine based adjuvant chemotherapy. Methods In total, 476 pathological specimens from eligible stage Ⅱ/Ⅲ CRCs were analyzed with IHC between 2016 and 2018, of which 63 CRCs were diagnosed with MMR protein deficiency. Clinicopathological features and overall survival (OS) were compared between these above two groups. Result The incidence of dMMR CRCs in our cohort was 13.2% (63/476). Immunohistochemistry (IHC) revealed two common dMMR IHC patterns in 63 dMMR CRCs. And dMMR type1 showed a higher proportion of women (P=0.001) and earlier pathological N stage (P=0.075). In the multivariate Cox regression model, POC (Postoperative chemotherapy) and dMMR were associated with a favor prognosis in CRC patients with stage II/III (HR 0.47, 95%CI 0.30-0.74, P=.001; HR 0.34, 95%CI 0.14-0.79, P=.013). However, adjuvant chemotherapy based on oxaliplatin and fluorouracil cannot prolong the OS of dMMR CRCs (P=0.182). Conclusions MMR protein appeared distinct associations with tumor staging, serum CEA level and tumor size. And MMR protein was an independent prognostic marker in patients with stage Ⅱ CRC, whereas dMMR CRC patients did not seem to benefit from oxaliplatin combined with fluorouracil-based adjuvant chemotherapy.

2021 ◽  
Author(s):  
An Shang ◽  
Zeyun Zhao ◽  
Zhaoyong Wang ◽  
Donglin Li ◽  
Yu Guo ◽  
...  

Abstract Background MSI CRCs were associated with better prognosis and limited predictive value for adjuvant chemotherapy. However, whether the same is true in Northeastern China is still unclear. The aim of the present study was to evaluate the association of clinicopathologic features and MMR/MSI status determined with immunohistochemistry analysis in Northeast China patients with stage Ⅱ/Ⅲ CRCs. Particularly, we sought to detect the relationship between MMR/MSI status and efficacy of oxaliplatin and fluoropyrimidine based adjuvant chemotherapy.MethodsIn total, 476 pathological specimens from eligible stage Ⅱ/Ⅲ CRCs were analyzed with IHC between 2016 and 2018, of which 63 CRCs were diagnosed with MMR protein deficiency. Clinicopathological features and overall survival (OS) were compared between these above two groups. Result The incidence of dMMR CRCs in our cohort was 13.2 % (63/476). Immunohistochemistry (IHC) revealed two common dMMR IHC patterns in 63 dMMR CRCs. And dMMR type1 showed a higher proportion of women (P=0.001) and earlier pathological N stage (P=0.075). In the multivariate Cox regression model, POC and dMMR were associated with a favor prognosis in CRC patients with stage II/III (HR 0.47, 95%CI 0.30-0.74, P=.001; HR 0.34, 95%CI 0.14-0.79, P=.013). However, adjuvant chemotherapy based on oxaliplatin and fluorouracil cannot prolong the OS of dMMR CRCs (P=0.182). Conclusions MMR protein appeared distinct associations with tumor staging, serum CEA level and tumor size. And MMR protein was an independent prognostic marker in patients with stage Ⅱ CRC, whereas dMMR CRC patients did not seem to benefit from oxaliplatin combined with fluorouracil-based adjuvant chemotherapy.


2020 ◽  
Vol 10 ◽  
Author(s):  
Yinchen Shen ◽  
Fang Hu ◽  
Changhui Li ◽  
Jianlin Xu ◽  
Runbo Zhong ◽  
...  

ObjectiveLarge-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of pulmonary cancer with poor survival. Optimal adjuvant chemotherapy for resected LCNEC is controversial till now; clinical features together with the prognostic factors in LCNEC should be clarified better.MethodsClinicopathological characteristics, driven genes’ status (EGFR, ALK, and ROS1), adjuvant chemotherapy strategy for 94 surgical resected LCNECs were extracted from digital database, tumor relapse or progression, and survival were analyzed with clinical profiles.ResultsDriven gene mutants were scarce in LCNEC, 8.3% (4/48) samples harbored EGFR mutations, 5.8% (3/52) with ALK positive, and none of ROS1 positive. A total of 44 patients suffered tumor relapse or progression during follow-up. Tumor/lymph node (N) stage, serum carcinoembryonic antigen (CEA) level before surgery, different adjuvant chemotherapies were associated with tumor relapse (P < 0.05); poorer disease-free survival (DFS) appeared in N2/stage III, serum CEA positive and pemetrexed based chemotherapy (P < 0.05); for overall survival (OS) analysis, the T/tumor stage, serum positive CEA/neuron-specific enolase (NSE) at baseline were associated with worse OS (P < 0.05). Moreover, in the multivariate analysis, N stage still acted as prognostic for DFS (P = 0.019); OS differed significantly in different T stages, chemotherapy selection and serum CEA levels after adjustment (P < 0.05).ConclusionClassical driven gene mutations were rare in LCNEC. Tumor N stage appeared as prognostic for DFS, while serum positive CEA, different adjuvant chemotherapy strategies, and T stage were independent prognostic factors for OS. Etoposide–platinum regime seemed to be a better choice which should be confirmed by further prospective investigations.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 369-369 ◽  
Author(s):  
D. J. Sargent ◽  
Q. Shi ◽  
B. M. Bot ◽  
M. B. Resnick ◽  
M. O. Meyers ◽  
...  

369 Background: A multi-center prospectively specified retrospective study Validating Indicators to Associate Recurrence (VITAR) is assessing the relationship between guanylyl cyclase C (GCC) gene expression in formalin fixed LNs and recurrence risk in stage II CC pts not treated with adjuvant chemotherapy. Here we report the preplanned initial analysis performed with 241 pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs tissues from untreated stage II CC pts diagnosed from 1999-2006 with at least 10 LN examined blinded to clinical outcomes. Cox regression models examined the relationship between GCC nodal status and the prespecified primary endpoint of recurrence risk. Results: Twenty-ninepts (12%) had a disease recurrence or cancer death, median follow-up was 60 months and median LNs examined was 15. The ratio of the number of GCC+ LNs over the total number of informative LNs (LNR) significantly predicted higher recurrence risk for 84 pts classified as high risk (HR, 2.38; p=0.02). The estimated 5-yr recurrence rates were 10% and 27% for the low and high risk group, respectively. After adjusting for age, T stage, number of LNs assessed, and MMR status, the significant association remained (HR, 2.61; 95% CI, 1.17-5.83; p=0.02). In a subset of 181 pts with negative margin, T3 tumor only and ≥12 LN examined, the GCC LNR had a HR for recurrence of 5.06 (95% CI 1.61-15.91, p=0.003), translating into 5-yr recurrence rates of 4% among low risk pts and 27% for the high-risk group. Conclusions: Our results suggest that GCC expression in LNs is a significant determinant of recurrence in appropriately staged CC pts not treated with adjuvant chemotherapy. The validation component of the study is ongoing. [Table: see text] [Table: see text]


Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2055
Author(s):  
Pei-Rung Yang ◽  
Ying-Ying Tsai ◽  
Ko-Jung Chen ◽  
Yao-Hsu Yang ◽  
Wei-Tai Shih

Background: Numerous studies have revealed that statins have antitumor effects in vivo and in vitro. However, few studies have explored the relationship between statin use and the mortality of gastric cancer (GC) patients after treatments. This study examines the relationship between statin use and the overall survival (OS) of GC patients after surgery and adjuvant chemotherapy, using data from the nationwide cohort database of Taiwan. Methods: All patients newly diagnosed with GC from 1999 to 2008 in Taiwan were identified from the Registry of Catastrophic Illness Patients Database. Through propensity score matching, statin users were matched to statin non-users at a 1:4 ratio. The relationship between statin use and the OS of patients with GC was estimated through Cox regression models. Results: The study cohort included 1835 patients with GC who had received therapies during the study period. The death numbers among statin users (defined as those who used more than 28 cumulative defined daily doses (cDDDs)) and statin non-users were 138 and 895, respectively. A dose–response association was noted between statin use and the OS of patients with GC after treatments. The adjusted hazard ratios were 0.62 (95% confidence intervals (CI), 0.50–0.78) and 0.34 (95% CI, 0.26–0.45) for statin users administered 28–167 cDDDs and >168 cDDDs, respectively, compared with no statin use (<28 cDDDs). Conclusions: This study highlights that statin use may dose-dependently improve the OS of patients with GC after surgery and adjuvant chemotherapy in Taiwan. Additional studies are required to confirm the efficacy and safety of statin use.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jun Bao ◽  
Yijiang Ni ◽  
Hui Qin ◽  
Li Xu ◽  
Zhijun Ge ◽  
...  

Objective.Rab27b is reported to correlate with cancer development and progression. However, the association between Rab27b expression and the clinical characteristics of colorectal cancer (CRC) is barely investigated.Methods.One-step quantitative reverse transcription-polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 113 CRC cases were performed to explore the relationship between Rab27b expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were executed to evaluate the prognosis of CRC.Results.The results demonstrated that the expression levels of Rab27b mRNA and protein were significantly higher in CRC tissues than that in matched noncancerous tissues (P<0.05). Rab27b protein expression in CRC was statistically correlated with serum CEA level (P=0.004), lymph node metastasis (P=0.001), distant metastasis (P=0.009), and TNM stage (P=0.001). Cox multifactor analysis and Kaplan-Meier method suggested that higher Rab27b protein expression (P=0.041) and tumor differentiation (P=0.001) were significantly associated with the overall survival of CRC patients.Conclusions.The data indicated that higher expression of Rab27b was observed in CRC tissues and Rab27b may be identified as a useful predictor of metastasis and prognosis for CRC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Parunya Chaiyawat ◽  
Areerak Phanphaisarn ◽  
Nutnicha Sirikaew ◽  
Jeerawan Klangjorhor ◽  
Viraporn Thepbundit ◽  
...  

AbstractOsteosarcoma is one of the most aggressive bone tumors in children and adolescents. Development of effective therapeutic options is still lacking due to the complexity of the genomic background. In previous work, we applied a proteomics-guided drug repurposing to explore potential treatments for osteosarcoma. Our follow-up study revealed an FDA-approved immunosuppressant drug, mycophenolate mofetil (MMF) targeting inosine-5′-phosphate dehydrogenase (IMPDH) enzymes, has an anti-tumor effect that appeared promising for further investigation and clinical trials. Profiling of IMPDH2 and hypoxanthine–guanine phosphoribosyltransferase (HPRT), key purine-metabolizing enzymes, could deepen understanding of the importance of purine metabolism in osteosarcoma and provide evidence for expanded use of MMF in the clinic. In the present study, we investigated levels of IMPDH2, and HPRT in biopsy of 127 cases and post-chemotherapy tissues in 20 cases of high-grade osteosarcoma patients using immunohistochemical (IHC) analysis. Cox regression analyses were performed to determine prognostic significance of all enzymes. The results indicated that low levels of HPRT were significantly associated with a high Enneking stage (P = 0.023) and metastatic status (P = 0.024). Univariate and multivariate analyses revealed that patients with low HPRT expression have shorter overall survival times [HR 1.70 (1.01–2.84), P = 0.044]. Furthermore, high IMPDH2/HPRT ratios were similarly associated with shorter overall survival times [HR 1.67 (1.02–2.72), P = 0.039]. Levels of the enzymes were also examined in post-chemotherapy tissues. The results showed that high IMPDH2 expression was associated with shorter metastasis-free survival [HR 7.42 (1.22–45.06), P = 0.030]. These results suggest a prognostic value of expression patterns of purine-metabolizing enzymes for the pre- and post-chemotherapy period of osteosarcoma treatment.


2021 ◽  
pp. 000313482110234
Author(s):  
Masaji Tani ◽  
Hiroya Iida ◽  
Hiromitsu Maehira ◽  
Haruki Mori ◽  
Toru Miyake ◽  
...  

Introduction Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy. While inflammation-related biomarkers influence patient survival after resection, it has not been known whether postoperative inflammations affect the survival of PDAC patients or not. Methods It was investigated whether the universal biomarkers on postoperative day (POD) 7 affect the survival of PDAC patients in the retrospective view, and univariate and multivariate analyses were performed via the Cox regression method. Results Overall, 108 consecutive patients underwent resection; 98 (90.7%) had T3 disease and 73 (67.6%) had lymph node metastases. Thirty-four patients (31.5%) experienced postoperative complications. Compared with preoperative values, the white blood cell count and C-reactive protein (CRP) level on POD 7 were significantly elevated ( P < .001 for both); conversely, the lymphocyte count was significantly reduced ( P < .001). Among 108 patients, 72 received adjuvant chemotherapy. The median overall survival was 21.0 months; the 5-year survival rate was 22.3%. On multivariate analysis, receiving adjuvant chemotherapy and low CRP levels on POD 7 (<7.6 mg/dL) were prognosticators of better survival. However, the CD classification was not a prognosticator of survival after resection. Conclusions Adjuvant chemotherapy and postoperative low CRP levels on POD 7 were prognosticators of better survival of PDAC patients after resection. Surgeons should be aware of managing postoperative infections because a high postoperative CRP level is related with unfavorable survival.


Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1154
Author(s):  
Hongjia Zhang ◽  
Seong-Gyu Jang ◽  
San Mar Lar ◽  
Ah-Rim Lee ◽  
Fang-Yuan Cao ◽  
...  

Starch is a major ingredient in rice, and the amylose content of starch significantly impacts rice quality. OsSS (starch synthase) is a gene family related to the synthesis of amylose and amylopectin, and 10 members have been reported. In the present study, a synteny analysis of a novel family member belonging to the OsSSIV subfamily that contained a starch synthase catalytic domain showed that three segmental duplications and multiple duplications were identified in rice and other species. Expression data showed that the OsSS gene family is involved in diverse expression patterns. The prediction of miRNA targets suggested that OsSS are possibly widely regulated by miRNA functions, with miR156s targeted to OsSSII-3, especially. Haplotype analysis exhibited the relationship between amylose content and diverse genotypes. These results give new insight and a theoretical basis for the improved amylose content and eating quality of rice.


2020 ◽  
Vol 45 (2) ◽  
pp. 180-193
Author(s):  
Ying Liu ◽  
Luping Wang ◽  
Xianfeng Han ◽  
Yang Wang ◽  
Xuefeng Sun ◽  
...  

Background: Hemodialysis is the main approach for renal replacement therapy in patients with end-stage renal disease (ESRD) in China. The timing of dialysis initiation is one of the key factors influencing patient survival and prognosis. Over the past decade, the relationship between the timing of dialysis initiation and mortality has remained unclear in patients with ESRD in China. Methods: Patients who commenced maintenance hemodialysis from 2009 to 2014 from 24 hemodialysis centers in Mainland China were enrolled in the study (n = 1,674). Patients were divided into 2 groups based on the year they started hemodialysis (patients who started hemodialysis from 2009 to 2011, and patients who started hemodialysis from 2012 to 2014). Analysis of the yearly change in the estimated glomerular filtration rate (eGFR) at the initiation of dialysis was performed for the 2 groups. Meanwhile, the patients were divided into 3 groups based on their eGFR at the initiation of dialysis (<4, 4–8, and >8 mL/min/1.73 m2). For these 3 groups, the relationship between the eGFR at the start of dialysis and mortality were analyzed. Results: The average eGFRs were 5.68 and 5.94 mL/min/1.73 m2 for 2009–2011 and 2012–2014, respectively. Compared with the 2009–2011 group, the proportion of patients with diabetes in 2012–2014 increased from 26.7 to 37.7%. The prognosis of patients with different eGFRs at the start of dialysis was analyzed using Kaplan-Meier survival curves. After adjusting for confounding factors through a Cox regression model, no significant difference was demonstrated among the 3 groups (<4 mL/min/1.73 m2 was used as the reference, in comparison with 4–8 mL/min/1.73 m2 [p = 0.681] and >8 mL/min/1.73 m2 [p = 0.403]). Conclusion: In Mainland China, the eGFR at the start of dialysis did not change significantly over time from 2008 to 2014 and had no association with the mortality of patients with ESRD.


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