Inverse effect of mucinous component on survival in stage III colorectal cancer

Ooki, Akira; Akagi, Kiwamu; Yatsuoka, Toshimasa; Asayama, Masako; Yamamoto, Gou; Nishimura, Yuichi; Yamaguchi, Kensei

doi:10.1002/jso.23742

Cited by 10 publications

(12 citation statements)

References 31 publications

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“…10,17,18 Conversely, other investigators have suggested that CAM is significantly associated with a worse prognosis than conventional adenocarcinoma. 19,20 In our study, we found that HCM patients had a between molecular features and prognosis. For instance, microsatellite instability (MSI) was confirmed more frequent in CAM and was closely associated with clinicopathological features.…”

Section: Discussionsupporting

confidence: 51%

“…Several studies have demonstrated that CAM has similar outcomes compared with conventional adenocarcinoma, with no impact on prognosis . Conversely, other investigators have suggested that CAM is significantly associated with a worse prognosis than conventional adenocarcinoma . In our study, we found that HCM patients had a remarkably worse long‐term survival compared with conventional HC patients.…”

Section: Discussioncontrasting

confidence: 39%

“…For instance, several studies have indicated that colorectal carcinoma with mucinous component (CAM) and conventional adenocarcinoma have similar outcomes, with no impact on prognosis . Conversely, other investigators have suggested that CAM is significantly associated with a worse prognosis than conventional adenocarcinoma …”

Section: Introductionmentioning

confidence: 99%

“…10,17,18 Conversely, other investigators have suggested that CAM is significantly associated with a worse prognosis than conventional adenocarcinoma. 19,20 To date, there are still no data available regarding the formation of clinicopathological characteristics and prognosis in HC with a mucinous component (HCM). Additionally, its prognostic factors remain largely unknown.…”

mentioning

confidence: 99%

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Prognostic significance of mucinous component in hilar cholangiocarcinoma after curative‐intent resection

et al. 2019

Journal of Surgical Oncology

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Background The presence of mucinous component has been indicated to have a prognostic value in adenocarcinoma. However, little is known regarding the clinicopathological characteristics and prognosis of hilar cholangiocarcinoma (HC) with mucinous component (HCM). Methods Between January 1996 and December 2014, a total of 61 HCM patients who underwent curative‐intent resection at West China Hospital were retrospectively reviewed. The clinicopathological characteristics and survival of these patients were compared with a large cohort of 217 surgically resected conventional HC patients during the same period. Results The clinicopathological characteristics of HCM were distinct from conventional HC, including higher CA19‐9 levels, larger tumor sizes, less differentiation, and a high frequency of liver parenchyma invasion, portal vein invasion, and lymphovascular invasion. HCM patients showed significantly worse recurrence‐free survival (13.4 vs 23.9 months; P = .011) and overall survival (18.2 vs 32.1 months; P = .019) compared with conventional HC patients. Multivariate analysis confirmed liver parenchyma invasion, N stage, surgical margin, and histological grade as independent prognostic factors influencing overall survival in HCM patients. Conclusion HCM showed distinct clinicopathological features, more aggressive biological behaviors, and poor prognosis in comparison with conventional HC. Therefore, the mucinous component is an adverse prognostic factor for HC.

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Section: Discussionsupporting

confidence: 51%

Section: Discussioncontrasting

confidence: 39%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Prognostic significance of mucinous component in hilar cholangiocarcinoma after curative‐intent resection

et al. 2019

Journal of Surgical Oncology

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“…MAC of CRC is an uncommon histological subtype of adenocarcinoma (approximately 5%-15%) [21] with more than 50% extracellular mucin within the tumor [22] . MAC is one of the most aggressive phenotypes of stage III CRC [23] . The clinical outcome of MAC is extremely poor once recurrence occurs [23] and is usually associated with a modest increase in mortality due to an increase in mucinous differentiation [24] .…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer

Fan

Teng

Shiau³

et al. 2015

Neoplasia

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STAT3 activation is associated with poor prognosis in human colorectal cancer (CRC). Our previous data demonstrated that regorafenib (Stivarga) is a pharmacological agonist of SH2 domain-containing phosphatase 1 (SHP-1) that enhances SHP-1 activity and induces apoptosis by targeting STAT3 signals in CRC. This study aimed to find a therapeutic drug that is more effective than regorafenib for CRC treatment. Here, we showed that SC-43 was more effective than regorafenib at inducing apoptosis in vitro and suppressing tumorigenesis in vivo. SC-43 significantly increased SHP-1 activity, downregulated p-STAT3Tyr705 level, and induced apoptosis in CRC cells. An SHP-1 inhibitor or knockdown of SHP-1 by siRNA both significantly rescued the SC-43–induced apoptosis and decreased p-STAT3Tyr705 level. Conversely, SHP-1 overexpression increased the effects of SC-43 on apoptosis and p-STAT3Tyr705 level. These data suggest that SC-43–induced apoptosis mediated through the loss of p-STAT3Tyr705 was dependent on SHP-1 function. Importantly, SC-43–enhanced SHP-1 activity was because of the docking potential of SC-43, which relieved the autoinhibited N-SH2 domain of SHP-1 and inhibited p-STAT3Tyr705 signals. Importantly, we observed that a significant negative correlation existed between SHP-1 and p-STAT3Tyr705expression in CRC patients (P = .038). Patients with strong SHP-1 and weak p-STAT3Tyr705 expression had significantly higher overall survival compared with patients with weak SHP-1 and strong p-STAT3Tyr705 expression (P = .029). In conclusion, SHP-1 is suitable to be a useful prognostic marker and a pharmacological target for CRC treatment. Targeting SHP-1-STAT3 signaling by SC-43 may serve as a promising pharmacotherapy for CRC.

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First‐line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component

et al. 2021

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Background To compare the efficacy of first‐line bevacizumab plus chemotherapy with cetuximab plus chemotherapy based on the stratification of metastatic colorectal cancer (mCRC) patients with mucinous adenocarcinoma (MA) or mucinous component (MC). Methods A retrospective study involving all mCRC patients receiving first‐line bevacizumab‐based or cetuximab‐based chemotherapy at our hospital from September 2013 to January 2020 was conducted. Overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR) were compared between the cetuximab‐chemotherapy group and the bevacizumab‐chemotherapy group on the basis of the conventional pathological classification of MA or MC. Results A total of 620 patients with mCRC were included in our study, consisting of 141 (22.7%) patients with MA/MC and 479 (77.3%) patients with non‐mucinous adenocarcinoma (NMA). In the MA/MC cohort, patients who were treated with bevacizumab‐based chemotherapy were associated with significantly better OS than those treated with cetuximab‐base chemotherapy (30.0 vs. 26.3 months, p = 0.002), irrespective of tumor sites. The efficacy of bevacizumab‐based chemotherapy was higher in nearly all subgroups as shown in the subgroup analysis. In the NMA cohort, median OS was better in the cetuximab plus chemotherapy group than that in the bevacizumab plus chemotherapy group (32.2 vs. 27.0 months, p = 0.005) for left‐side mCRC patients, whereas OS was significantly longer in the bevacizumab plus chemotherapy group for right‐side mCRC patients (26.0 vs. 20.9 months, p = 0.013). Conclusion Conventional pathological classification (e.g. MA/MC) should be considered when tailoring the individualized optimal treatment for mCRC. Bevacizumab plus chemotherapy as first‐line therapy may be the optimal option for patients with MA/MC.

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Inverse effect of mucinous component on survival in stage III colorectal cancer

Abstract: Although ACM is similar to CAC with regard to estimated risk of recurrence, the outcome is extremely poor once recurrence occurs and is identical to MAC; one of the most aggressive phenotypes of stage III CRC. Thus, both MAC and ACM are adverse prognostic factors for OS.

Cited by 10 publications

References 31 publications

Prognostic significance of mucinous component in hilar cholangiocarcinoma after curative‐intent resection

Prognostic significance of mucinous component in hilar cholangiocarcinoma after curative‐intent resection

Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer

First‐line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component

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