Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy

Li, Chien‐Feng; He, Hong; Wang, Jaw‐Yuan; Huang, Hsuan Ying; Wu, Ting; Hsing, Chung-Hsi; Lee, Sung Wei; Lee, Hao Hsien; Fang, Jui Lung; Huang, Wen-Cheng; Chen, Shang Hung

doi:10.1136/jclinpath-2014-202551

Cited by 25 publications

(22 citation statements)

References 33 publications

(28 reference statements)

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“…All patients were pathologically diagnosed with a rectal adenocarcinoma using a colonendoscopic biopsy, lacking evidence of distant metastasis on imaging examination including chest X-radiography and/or abdominopelvic CT. The criteria for the clinicopathologic evaluation were essentially identical as previously described 26-28. In general, all patients received had preoperative 5-fluorouracil-baed chemotherapy concomitant to radiotherapy with a total dose of 45 Gy in 25 fractions over a period of five weeks.…”

Section: Methodsmentioning

confidence: 99%

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Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Lee¹,

Wei²,

Tian³

et al. 2017

J. Cancer

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Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT.Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS).Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison.Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

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Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry of FFPE tissue sections was performed as previously described 26-28. Briefly, tissue sections from Pre-Tx rectal tumor biopsies were deparaffinized and rehydrated for TCN1 immunostaining.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Lee¹,

Wei²,

Tian³

et al. 2017

J. Cancer

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“…As previously described, tumor specimens at initial diagnosis were routinely deparaffinized, rehydrated, heated, quenched, and washed for immunohistochemical staining. 12,13 After epitope retrieval, tumor specimens were incubated for 1 hour with primary antibody recognizing PCSK1 (Sigma, clone 3D2, 1:50). The immunoexpression levels of PCSK1 in all tumor specimens were scored by two independent pathologists of the addition of secondary antibody and hematoxylin staining.…”

Section: Pcsk1 Immunohistochemical Analysismentioning

confidence: 99%

<p>PCSK1 Overexpression in Rectal Cancer Correlates with Poor Response to Preoperative Chemoradiotherapy and Prognosis</p>

Chou¹,

Chen²,

Lin³

et al. 2020

OTT

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Background: In a data mining search for potential therapeutic targets to improve the outcome of rectal cancer, we identified PCSK1 as the cell-cell signaling gene most significantly associated with poor response to concurrent chemoradiotherapy (CCRT). This study aims to investigate the prognostic value of PCSK1 expression in rectal cancer patients who underwent neoadjuvant CCRT. Methods: Endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery were assessed immunohistochemically for PCSK1 expression, and H-scores were determined. Expression levels of PCSK1 were further analyzed for correlations with clinicopathologic features, tumor regression grade, metastasis-free survival, disease-specific survival, and recurrence-free survival. Results: PCKS1 overexpression was significantly associated with pretreatment tumor status (T3-4; p = 0.009), pretreatment nodal status (N1-2; p < 0.001), posttreatment tumor status (T3-4; p < 0.001), posttreatment nodal status (N1-2; p < 0.001), vascular invasion (p = 0.003), and perineurial invasion (p = 0.023). PCKS1 overexpression was also found to be significantly associated with a lower degree of tumor regression (p < 0.001). In the univariate analysis, PCSK1 overexpression was significantly associated with lower disease-specific survival, metastasis-free survival, and recurrence-free survival (p < 0.005). PCSK1 overexpression remained an independent prognostic factor of lower disease-specific survival (p = 0.003; hazard ratio, 5.478) in the multivariate analysis. Conclusion: Determination of PCSK1 overexpression may be useful for identifying rectal cancer patients at risk for a poor response and worse survival after CCRT.

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“…Rectal cancer is defined as a cancerous lesion of the colon distal to the rectosigmoid junction [2], which accounts for approximately 25-30 % of all colorectal cancer cases. Incidence of rectal cancer is considered as the close correlation to the western lifestyle and dietary factors.…”

Section: Introductionmentioning

confidence: 99%

The influence of neoadjuvant therapy for the prognosis in patients with rectal carcinoma: a retrospective study

Peng

Wang

et al. 2015

Tumor Biol.

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Rectal cancer, defined as a cancerous lesion of the colon distal to the rectosigmoid junction, is the fourth most common cancer cause of death globally. There were 474 patients with rectal cancer who underwent surgery between October 2007 and May 2013 enrolled in our center. Patients were respectively categorized by neoadjuvant therapy. This study aimed to explore the predictive factors that affected the Progression-free survival and overall survival of the patients with rectal cancer. Clinical characteristics of patients were compared with the groups and potential prognostic factors were analyzed by SPSS 19.0. In our study, neoadjuvant therapy increased the anus-retained rate (64.4 vs 53.4 % P = 0.016) and remission rate in the treatment group, compared to the non-treatment group (62.6 vs 34.8 %; P = 0.000). The neoadjuvant concurrent chemoradiotherapy, more operative duration, anus retained and micturition damaged are positive prognostic factors of PFS to patients. Poor differentiation, the tumor of ulcer, invasive, and pT4 stage, contributed the poor factors for PFS of patients (P< 0.05). Additionally, the patients with neoadjuvant concurrent chemoradiotherapy and adjuvant chemotherapy underwent the better prognosis of OS. Adjuvant chemotherapy cannot increase PFS of the patients who accepted neoadjuvant therapy after surgery get pCR, but can improve OS. The anus-retained and neoadjuvant radiotherapy, duration of surgery in rectal cancer have the positive correlation. Micturition damaged and neoadjuvant radiotherapy were positively correlated as well. In conclusion, adjuvant chemotherapy does not improve the PFS of patients with pCR to neoadjuvant therapy, but is good for OS. Further prospective and large population-based clinical studies are needed to establish clinical guidelines for the use of neoadjuvant therapy and adjuvant chemotherapy in patients with rectal cancer.

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Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy

Abstract: High expression of FGFR2 is correlated with advanced tumour stage, poor therapeutic response and worse survival in rectal cancer patients receiving neoadjuvant CCRT. These findings indicate that FGFR2 is a prognostic factor for treating rectal cancer.

Cited by 25 publications

References 33 publications

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

<p>PCSK1 Overexpression in Rectal Cancer Correlates with Poor Response to Preoperative Chemoradiotherapy and Prognosis</p>

The influence of neoadjuvant therapy for the prognosis in patients with rectal carcinoma: a retrospective study

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