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Sonic Hedgehog (SHH) Status Determines the Chemotherapeutic Outcomes in High Risk Stage II and III Head and Neck Cancer Patients

45 Pages Posted: 5 Sep 2018

See all articles by Abu Shadat M Noman

Abu Shadat M Noman

University of Chittagong

Rashed R Parag

University of Chittagong - Department of Biochemistry and Molecular Biology

Irfanur Rashid

University of Chittagong

Zillur Rahman

Chittagong Medical College & Hospital

Ali Asgar Chowdhury

Chittagong Medical College & Hospital

Afrin Sultana

University of Chittagong

ChandSultana Jerin

University of Chittagong

Ayesha Siddiqua

University of Chittagong

Lutfur Rahman

University of Chittagong

Afsana Shirin

University of Chittagong

Junayed Nayeem

University of Chittagong

Reaz Mahmud

University of Chittagong

Sonam Akther

University of Chittagong

Rajib Shil

University of Chittagong

Ikram Hossain

University of Chittagong

Sharmin Alam

University of Chittagong

Afrina Chowdhury

University of Chittagong

Shabnam Basher

University of Chittagong

Abul Hasan

University of Chittagong

Shammy Bithy

University of Chittagong

Jannatul Aklima

University of Chittagong

Mizanur Rahman

University of Chittagong

Tahmina Banu

Chittagong Research Institute of Children Surgery

Bedri Karakas

King Faisal Specialist Hospital and Research Centre - Translational Cancer Research Section; King Faisal Specialist Hospital and Research Centre - Department of Molecular Oncology

Herman Yeger

University of Toronto - Program in Developmental and Stem Cell Biology

Walid Farhat

University of Toronto - Program in Developmental and Stem Cell Biology

Syed S. Islam

King Faisal Specialist Hospital and Research Centre - Department of Molecular Oncology; University of Toronto - Program in Developmental and Stem Cell Biology; Park View Specialized Hospital

More...

Abstract

Importance: Head and neck squamous cell carcinoma (HNSCC) still poses therapeutic challenges due to local recurrence and metastasis.  

Objective: Explore a reliable biomarker to stratify patients who benefit from adjuvant chemotherapy in HNSCC patients.  

Design: We analyzed a cohort of HNSCC patients to identify potential candidate biomarker and analyzed overall survival (OS) and disease-free survival (DFS) of these patients who benefit from adjuvant chemotherapy.  

Results: : Sonic hedgehog (Shh), a secreted signaling molecule identified as a potential candidate biomarker in our analysis. A group of HNSCC patients (106/183) were negative to Shh. In the discovery dataset, the OS (HR 3·231, CI 1·23-8·53, p<0·017) and DFS (HR 3·774, CI 1·6178·007, p<0·0021) remained lower among Shh-neg patients tumors. In the TCGA validation dataset (n=312), the OS (35% vs 50%, p<0·046) and DFS (24% vs 85%, p<0·002) remained lower in the Shh-neg patients, corroborating our discovery cohort. Among the patients with stage II and III tumors, the 5-year OS (80% vs 37% and 70% vs 20%) and DFS (55% vs 26% and 27% vs 8%) remained lower. When patients stratified with or without adjuvant chemotherapy in the stage II and stage III tumors for disease progression, the 5-year DFS were longer in the Shh-neg tumors who were treated with adjuvant chemotherapy (stage II; 80% vs 50%, p<0.019, stage III; 70% vs 55%, p< 0.11).

Conclusions: This study identified that lack of Shh expression in a group of HNSCC patients with stage II and stage III tumors likely to benefit from adjuvant chemotherapy.  

Funding Statement: Grant-in-Aid from Bangladesh Medical Research Council (BMRC), and University Grant Commission (UGC), Ministry of Education of Bangladesh with the assistance of the World Bank under Higher Education Quality Enhancement Project (HEQEP)– Window -4 (Grant Id. CP4023).

Declaration of Interests: The authors declare that they have no conflict of interests.

Ethics Approval Statement: This retrospective study included 183 patients (CMCH cohort, discovery cohort) with stage I to IV HNSCC, who received treatment at Chittagong Medical College and Hospital (CMCH) affiliated with The University of Chittagong, Bangladesh between September 2014 and October 2016. The institutional review board of the participating institute approved the study. All patients recruited in this study were given a written consent.

Keywords: HNSCC, Shh, DFS, OS, Nrf2

Suggested Citation

Noman, Abu Shadat M and Parag, Rashed R and Rashid, Irfanur and Rahman, Zillur and Chowdhury, Ali Asgar and Sultana, Afrin and Jerin, ChandSultana and Siddiqua, Ayesha and Rahman, Lutfur and Shirin, Afsana and Nayeem, Junayed and Mahmud, Reaz and Akther, Sonam and Shil, Rajib and Hossain, Ikram and Alam, Sharmin and Chowdhury, Afrina and Basher, Shabnam and Hasan, Abul and Bithy, Shammy and Aklima, Jannatul and Rahman, Mizanur and Banu, Tahmina and Karakas, Bedri and Yeger, Herman and Farhat, Walid and Islam, Syed S., Sonic Hedgehog (SHH) Status Determines the Chemotherapeutic Outcomes in High Risk Stage II and III Head and Neck Cancer Patients (July 17, 2018). Available at SSRN: https://ssrn.com/abstract=3216194 or http://dx.doi.org/10.2139/ssrn.3216194

Abu Shadat M Noman

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Rashed R Parag

University of Chittagong - Department of Biochemistry and Molecular Biology

4331
Bangladesh

Irfanur Rashid

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Zillur Rahman

Chittagong Medical College & Hospital

57, K.B. FAZLUL KADER ROAD
P.S- PANCHLAISH, P.O- CHAWKBAZAR
CHITTAGONG
Bangladesh

Ali Asgar Chowdhury

Chittagong Medical College & Hospital

Bangladesh

Afrin Sultana

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

ChandSultana Jerin

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Ayesha Siddiqua

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Lutfur Rahman

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Afsana Shirin

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Junayed Nayeem

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Reaz Mahmud

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Sonam Akther

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Rajib Shil

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Ikram Hossain

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Sharmin Alam

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Afrina Chowdhury

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Shabnam Basher

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Abul Hasan

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Shammy Bithy

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Jannatul Aklima

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Mizanur Rahman

University of Chittagong

Hathazari, Chittagong, Bangladesh
Chittagong, Chittagong 4331
Bangladesh

Tahmina Banu

Chittagong Research Institute of Children Surgery

Bangladesh

Bedri Karakas

King Faisal Specialist Hospital and Research Centre - Translational Cancer Research Section ( email )

Riyadh
Saudi Arabia

King Faisal Specialist Hospital and Research Centre - Department of Molecular Oncology ( email )

Saudi Arabia

Herman Yeger

University of Toronto - Program in Developmental and Stem Cell Biology

555 University Avenue
Toronto, Ontario M5G 1X8
Canada

Walid Farhat

University of Toronto - Program in Developmental and Stem Cell Biology

555 University Avenue
Toronto, Ontario M5G 1X8
Canada

Syed S. Islam (Contact Author)

King Faisal Specialist Hospital and Research Centre - Department of Molecular Oncology ( email )

Saudi Arabia

University of Toronto - Program in Developmental and Stem Cell Biology ( email )

555 University Avenue
Toronto, Ontario M5G 1X8
Canada

Park View Specialized Hospital ( email )

Bangladesh